ACR 2024

WASHINGTON — Immune checkpoint inhibitor (ICI) therapy does not increase mortality in people with preexisting autoimmune diseases, new research has found. 

Results from a large database analysis of patients with and without autoimmune diseases suggest it is safe to treat them with ICI if they develop a cancer for which it is indicated, Greg Challener, MD, a postdoctoral fellow at the Rheumatology and Allergy Clinical Epidemiology Research Center, Massachusetts General Hospital, Boston, said at the American College of Rheumatology 2024 Annual Meeting.

“One message is that, when rheumatologists are asked by oncologists about patients with rheumatoid arthritis or vasculitis or other autoimmune diseases and whether it’s safe to treat them with immune checkpoint inhibitors, this result provides some evidence that it probably is safe…. Checkpoint inhibitors are really incredible drugs, and they’ve improved mortality for a lot of cancers, particularly melanoma, and so I think there should be a pretty high threshold for us to say a patient shouldn’t receive them because of an autoimmune condition,” he told this news organization.

Another implication, Challener said, is that people with autoimmune diseases shouldn’t routinely be excluded from clinical trials of ICIs. Currently they are excluded because of concerns about exacerbation of underlying autoimmunity, possible interference between the ICI and the immunosuppressive drugs used to treat the autoimmune condition, and a theoretical risk for serious adverse events. 

“Clinical trials are continuing to exclude these patients, and they paint with a very broad brush anyone with underlying autoimmunity ... I’m hoping that that changes. I don’t think there’s a great evidence base to support that practice, and it’s unfortunate that patients with underlying autoimmune diseases are excluded from important studies,” Challener said.

Asked to comment, session moderator Matlock Jeffries, MD, director of the Arthritis Research Unit at the Oklahoma Medical Research Foundation, Oklahoma City, told this news organization that he agrees the data are generally reassuring. “If one of our patients gets cancer and their oncologist wants to use a checkpoint inhibitor, we’d obviously still monitor them for complications, but we wouldn’t automatically assume the combination of a checkpoint inhibitor and autoimmune disease would increase their mortality.” 

 

No Difference in Mortality for Those With and Without Autoimmune Disease

Challener and colleagues used administrative health data from the TriNetX Diamond network of 92 US healthcare sites with 212 million patients. All patients included in the study were receiving anti-programmed death protein 1/programmed death ligand 1 to treat malignancies involving the skin, lung/bronchus, digestive organs, or urinary tract. The study population also had at least one rheumatologic, gastrointestinal, neurologic, dermatologic, or endocrine autoimmune disease.

Propensity score matching between those with and without autoimmune disease was performed for about 100 covariates. Prior to the matching, the autoimmune disease group had significantly higher rates of cardiovascular and other comorbidities. The matching yielded 23,714 individuals with autoimmune disease and the same number without who had similar demographics and comorbidity rates, as well as malignancy type, alcohol/tobacco use, and medication use. 

At a median follow-up of 250 days, the risk for mortality prior to propensity matching was 40.0% in the autoimmune disease group and 38.1% for those without, a significant difference with hazard ratio 1.07 (95% CI, 1.05-1.10). But after the matching, the difference was no longer significant: 39.8% vs 40.2%, respectively (0.97, 0.94-1.00). 

The Kaplan-Meier curves for survival probability for those with or without autoimmune disease were nearly superimposed, showing no difference up to 1600 days. An analysis of just the patients with rheumatic diseases yielded similar results, Challener said. 

 

Some Caveats About the Data

Jeffries, who is also an associate professor of medicine at the University of Oklahoma Health Sciences Center, Oklahoma City, and the Oklahoma VA, said he would like to see additional data on outcomes, both for the autoimmune conditions and the cancers. Challener said there are plans to look at other hard endpoints such as myocardial infarction and end-stage renal disease, but that the database is limited. 

Both Challener and Jeffries also cautioned that the reassurance may not apply to patients with active disease. 

“One thing this research doesn’t address is whether active autoimmune disease might have a different outcome compared to more kind of quiet disease…. If you have a patient who has extremely active rheumatoid arthritis or extremely active giant cell arthritis, for instance, I think that could be more challenging. I would be frightened to put a patient with really active GCA on pembrolizumab or say that it’s safe without their disease being controlled. But for someone who has well-controlled disease or minimally active disease, this is very reassuring,” Challener told this news organization.

“I think this may also be important in that it’s a good argument to tell the drug companies to include autoimmune patients in these trials so we can get better data,” Jeffries said.

Challener and Jeffries had no relevant disclosures. 
 

A version of this article appeared on Medscape.com.

WASHINGTON — Immune checkpoint inhibitor (ICI) therapy does not increase mortality in people with preexisting autoimmune diseases, new research has found. 

Results from a large database analysis of patients with and without autoimmune diseases suggest it is safe to treat them with ICI if they develop a cancer for which it is indicated, Greg Challener, MD, a postdoctoral fellow at the Rheumatology and Allergy Clinical Epidemiology Research Center, Massachusetts General Hospital, Boston, said at the American College of Rheumatology 2024 Annual Meeting.

“One message is that, when rheumatologists are asked by oncologists about patients with rheumatoid arthritis or vasculitis or other autoimmune diseases and whether it’s safe to treat them with immune checkpoint inhibitors, this result provides some evidence that it probably is safe…. Checkpoint inhibitors are really incredible drugs, and they’ve improved mortality for a lot of cancers, particularly melanoma, and so I think there should be a pretty high threshold for us to say a patient shouldn’t receive them because of an autoimmune condition,” he told this news organization.

Another implication, Challener said, is that people with autoimmune diseases shouldn’t routinely be excluded from clinical trials of ICIs. Currently they are excluded because of concerns about exacerbation of underlying autoimmunity, possible interference between the ICI and the immunosuppressive drugs used to treat the autoimmune condition, and a theoretical risk for serious adverse events. 

“Clinical trials are continuing to exclude these patients, and they paint with a very broad brush anyone with underlying autoimmunity ... I’m hoping that that changes. I don’t think there’s a great evidence base to support that practice, and it’s unfortunate that patients with underlying autoimmune diseases are excluded from important studies,” Challener said.

Asked to comment, session moderator Matlock Jeffries, MD, director of the Arthritis Research Unit at the Oklahoma Medical Research Foundation, Oklahoma City, told this news organization that he agrees the data are generally reassuring. “If one of our patients gets cancer and their oncologist wants to use a checkpoint inhibitor, we’d obviously still monitor them for complications, but we wouldn’t automatically assume the combination of a checkpoint inhibitor and autoimmune disease would increase their mortality.” 

 

No Difference in Mortality for Those With and Without Autoimmune Disease

Challener and colleagues used administrative health data from the TriNetX Diamond network of 92 US healthcare sites with 212 million patients. All patients included in the study were receiving anti-programmed death protein 1/programmed death ligand 1 to treat malignancies involving the skin, lung/bronchus, digestive organs, or urinary tract. The study population also had at least one rheumatologic, gastrointestinal, neurologic, dermatologic, or endocrine autoimmune disease.

Propensity score matching between those with and without autoimmune disease was performed for about 100 covariates. Prior to the matching, the autoimmune disease group had significantly higher rates of cardiovascular and other comorbidities. The matching yielded 23,714 individuals with autoimmune disease and the same number without who had similar demographics and comorbidity rates, as well as malignancy type, alcohol/tobacco use, and medication use. 

At a median follow-up of 250 days, the risk for mortality prior to propensity matching was 40.0% in the autoimmune disease group and 38.1% for those without, a significant difference with hazard ratio 1.07 (95% CI, 1.05-1.10). But after the matching, the difference was no longer significant: 39.8% vs 40.2%, respectively (0.97, 0.94-1.00). 

The Kaplan-Meier curves for survival probability for those with or without autoimmune disease were nearly superimposed, showing no difference up to 1600 days. An analysis of just the patients with rheumatic diseases yielded similar results, Challener said. 

 

Some Caveats About the Data

Jeffries, who is also an associate professor of medicine at the University of Oklahoma Health Sciences Center, Oklahoma City, and the Oklahoma VA, said he would like to see additional data on outcomes, both for the autoimmune conditions and the cancers. Challener said there are plans to look at other hard endpoints such as myocardial infarction and end-stage renal disease, but that the database is limited. 

Both Challener and Jeffries also cautioned that the reassurance may not apply to patients with active disease. 

“One thing this research doesn’t address is whether active autoimmune disease might have a different outcome compared to more kind of quiet disease…. If you have a patient who has extremely active rheumatoid arthritis or extremely active giant cell arthritis, for instance, I think that could be more challenging. I would be frightened to put a patient with really active GCA on pembrolizumab or say that it’s safe without their disease being controlled. But for someone who has well-controlled disease or minimally active disease, this is very reassuring,” Challener told this news organization.

“I think this may also be important in that it’s a good argument to tell the drug companies to include autoimmune patients in these trials so we can get better data,” Jeffries said.

Challener and Jeffries had no relevant disclosures. 
 

A version of this article appeared on Medscape.com.

WASHINGTON — Immune checkpoint inhibitor (ICI) therapy does not increase mortality in people with preexisting autoimmune diseases, new research has found. 

Results from a large database analysis of patients with and without autoimmune diseases suggest it is safe to treat them with ICI if they develop a cancer for which it is indicated, Greg Challener, MD, a postdoctoral fellow at the Rheumatology and Allergy Clinical Epidemiology Research Center, Massachusetts General Hospital, Boston, said at the American College of Rheumatology 2024 Annual Meeting.

“One message is that, when rheumatologists are asked by oncologists about patients with rheumatoid arthritis or vasculitis or other autoimmune diseases and whether it’s safe to treat them with immune checkpoint inhibitors, this result provides some evidence that it probably is safe…. Checkpoint inhibitors are really incredible drugs, and they’ve improved mortality for a lot of cancers, particularly melanoma, and so I think there should be a pretty high threshold for us to say a patient shouldn’t receive them because of an autoimmune condition,” he told this news organization.

Another implication, Challener said, is that people with autoimmune diseases shouldn’t routinely be excluded from clinical trials of ICIs. Currently they are excluded because of concerns about exacerbation of underlying autoimmunity, possible interference between the ICI and the immunosuppressive drugs used to treat the autoimmune condition, and a theoretical risk for serious adverse events. 

“Clinical trials are continuing to exclude these patients, and they paint with a very broad brush anyone with underlying autoimmunity ... I’m hoping that that changes. I don’t think there’s a great evidence base to support that practice, and it’s unfortunate that patients with underlying autoimmune diseases are excluded from important studies,” Challener said.

Asked to comment, session moderator Matlock Jeffries, MD, director of the Arthritis Research Unit at the Oklahoma Medical Research Foundation, Oklahoma City, told this news organization that he agrees the data are generally reassuring. “If one of our patients gets cancer and their oncologist wants to use a checkpoint inhibitor, we’d obviously still monitor them for complications, but we wouldn’t automatically assume the combination of a checkpoint inhibitor and autoimmune disease would increase their mortality.” 

 

No Difference in Mortality for Those With and Without Autoimmune Disease

Challener and colleagues used administrative health data from the TriNetX Diamond network of 92 US healthcare sites with 212 million patients. All patients included in the study were receiving anti-programmed death protein 1/programmed death ligand 1 to treat malignancies involving the skin, lung/bronchus, digestive organs, or urinary tract. The study population also had at least one rheumatologic, gastrointestinal, neurologic, dermatologic, or endocrine autoimmune disease.

Propensity score matching between those with and without autoimmune disease was performed for about 100 covariates. Prior to the matching, the autoimmune disease group had significantly higher rates of cardiovascular and other comorbidities. The matching yielded 23,714 individuals with autoimmune disease and the same number without who had similar demographics and comorbidity rates, as well as malignancy type, alcohol/tobacco use, and medication use. 

At a median follow-up of 250 days, the risk for mortality prior to propensity matching was 40.0% in the autoimmune disease group and 38.1% for those without, a significant difference with hazard ratio 1.07 (95% CI, 1.05-1.10). But after the matching, the difference was no longer significant: 39.8% vs 40.2%, respectively (0.97, 0.94-1.00). 

The Kaplan-Meier curves for survival probability for those with or without autoimmune disease were nearly superimposed, showing no difference up to 1600 days. An analysis of just the patients with rheumatic diseases yielded similar results, Challener said. 

 

Some Caveats About the Data

Jeffries, who is also an associate professor of medicine at the University of Oklahoma Health Sciences Center, Oklahoma City, and the Oklahoma VA, said he would like to see additional data on outcomes, both for the autoimmune conditions and the cancers. Challener said there are plans to look at other hard endpoints such as myocardial infarction and end-stage renal disease, but that the database is limited. 

Both Challener and Jeffries also cautioned that the reassurance may not apply to patients with active disease. 

“One thing this research doesn’t address is whether active autoimmune disease might have a different outcome compared to more kind of quiet disease…. If you have a patient who has extremely active rheumatoid arthritis or extremely active giant cell arthritis, for instance, I think that could be more challenging. I would be frightened to put a patient with really active GCA on pembrolizumab or say that it’s safe without their disease being controlled. But for someone who has well-controlled disease or minimally active disease, this is very reassuring,” Challener told this news organization.

“I think this may also be important in that it’s a good argument to tell the drug companies to include autoimmune patients in these trials so we can get better data,” Jeffries said.

Challener and Jeffries had no relevant disclosures. 
 

A version of this article appeared on Medscape.com.

WASHINGTON — An implantable vagus nerve stimulation (VNS) device effectively treats moderate to severe rheumatoid arthritis (RA) in patients who had previously failed at least one biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD), according to results from a phase 3 trial.

Of the 242 patients in the RESET-RA study, all received the VNS device implant but were blinded as to whether the device was turned on. At 12 weeks, 35.2% of patients receiving daily stimulation achieved 20% improvement in American College of Rheumatology response criteria (ACR20) compared with 24.2% of those with an inactive device. The response was more pronounced among patients with exposure to only one prior b/tsDMARD. A greater proportion of patients in the overall treatment group also reached low disease activity or remission compared with those who did not receive stimulation. 

The research was presented as a late-breaking poster at the ACR 2024 Annual Meeting.

“This is a particularly tough-to-treat patient population, since the patients enrolled were considered refractory to biologic therapy,” said Elena Schiopu, MD, professor of medicine in the Division of Rheumatology and director of clinical trials at the Medical College of Georgia at Augusta University. More than one third of patients in the study had tried three or more b/tsDMARDs prior to the study. “I’m pretty excited about these results,” she added. Schiopu was a RESET-RA institutional principal investigator and enrolled two patients in the trial.

These positive results are a first for VNS treatment in rheumatic diseases. Previous studies demonstrating the potential therapeutic effect of this implant approach have largely been open-label, proof-of-concept, or pilot studies. Noninvasive, wearable stimulation devices have also shown promise in open-label studies; however, a sham-controlled trial published in 2023 showed that transcutaneous vagus nerve stimulation on the ear was no more effective than placebo. 

 

But How Does It Work?

The device, developed by SetPoint Medical in Valencia, California, is about the size of a multivitamin and implanted in an outpatient setting. During the 45-minute procedure, surgeons isolate the vagus nerve on the left side of the neck and place the nerve stimulator with a silicone positioning pod to hold it in place.

The device is programmed to deliver stimulation for 1 minute every day and needs charging for only 10 minutes once a week, which is done remotely with a necklace.

The device takes advantage of the vagus nerve’s anti-inflammatory properties, stimulating the nerve to help regulate an overactive immune system of someone with RA, explained David Chernoff, MD, Setpoint Medical’s chief medical officer. 

“We’re recapitulating what nature has developed over millions of years, which is the nexus between the brain and the immune system, which happens to be mediated by the vagus nerve,” he told Medscape Medical News. 

This novel VNS approach also does not have the same immunosuppressive safety concerns as drugs commonly used to treat RA, he said. 

“We’re able to adjust the amount of inflammation, but we don’t cause the host defense issues” that are present with some of these drugs, he continued.

SetPoint Medical’s pilot study of the device in 14 patients showed promising results. Five of 10 patients randomly assigned to active VNS over 12 weeks showed clinical improvements, measured by 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP) and the Clinical Disease Activity Index. In the remaining four patients who received sham stimulation — where the device was implanted but not activated — there were no clinical disease improvements.

 

RESET-RA Details

The most recent, much larger phase 3 study enrolled patients from 41 sites in the United States. Patients were on average 56 years old and had a body mass index of 30; 86% were women. A total of 39% had previously tried one b/tsDMARD, 22% had tried two, and 39% had tried three or more. Patients, on average, had 15 tender joints and 10 swollen joints. Patients discontinued their prior b/tsDMARD before the procedure and remained on conventional DMARDS during the trial, including methotrexate, hydroxychloroquine, and sulfasalazine.

The researchers randomly assigned patients 1:1 to active (treatment) or nonactive (control) stimulation. 

“The perception of stimulation varies from patient to patient, which itself is helpful in blinding as there is no expected perception of whether or how stimulation will be felt,” Chernoff explained. The 1-minute stimulation was scheduled in the early hours of the morning, when a patient typically would be asleep, he said.

Patients were excluded from the analysis if they were rescued by steroids or b/tsDMARDs through week 12. After week 12, the control group was switched to stimulation and efficacy was reassessed at week 24.

 

Higher ACR20 Response Rate, Lower Disease Activity

Beyond meeting the primary endpoint of ACR20 response, patients on the active stimulation group showed lower disease activity at week 12. Compared with 15.8% of patients in the control group, 27% of those in the treatment group achieved a DAS28-CRP ≤ 3.2. 

The active stimulation was particularly effective in patients who had experience with only one prior b/tsDMARD. In this subset of patients, 44.2% in the treatment group achieved ACR20 compared with 19.0% in the control group.

During this sham-controlled trial period, 13.1% of patients in the treatment group and 18.3% of patients in the control group reported an adverse event (AE) related to the procedure or device, most commonly vocal cord paresis or dysphonia. In the treatment group, 8.2% reported stimulation-related AEs, most commonly mild/moderate pain that was managed by adjusting the stimulation level. 

Serious adverse events (SAEs) were relatively rare, with four treatment-related SAEs across both study groups. No AEs led to study discontinuation through week 24.

The 12-week results mirror those of the initial Humira and Enbrel trials in the late 1990s and early 2000s, Schiopu said, although in those trials, the patients were naive to biologics, and some were naive to methotrexate. A more appropriate comparison, she said, would be biologic-experienced populations.

At week 24, the percentage of patients achieving ACR20 further increased to 51.5% in the treatment group and to 53.1% in the previous control group who were now crossed over to active stimulation. In this secondary period, patients could add any additional therapies like steroids or b/tsDMARDs. At 24 weeks, 81% of patients remained on stimulation without needing additional medication, beyond their continued background DMARDs. 

The results also show “a continuum of improvement over time,” Schiopu said, where response rates climbed through week 24. 

Schiopu is particularly excited about the potential to use this stimulation device in older patients, who have perhaps been on immunosuppressant drugs for decades. 

“Aside from being chronically immunosuppressed, their immune system is more tired [due to age],” she said. With VNS therapies like SetPoint’s, “we could offer [these patients] a lesser immunosuppressive alternative that is still immune-modular enough to manage their RA.”

Schiopu is a consultant for Johnson & Johnson and reported receiving research funding for serving as an institutional principal investigator for SetPoint, Galapagos, Johnson & Johnson, Boehringer Ingelheim, Lilly, argenx, EMD Serono, Priovant, Novartis, Bristol Myers Squibb, Zena Pharmaceuticals, and Horizon/Amgen.

 

A version of this article appeared on Medscape.com.

WASHINGTON — An implantable vagus nerve stimulation (VNS) device effectively treats moderate to severe rheumatoid arthritis (RA) in patients who had previously failed at least one biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD), according to results from a phase 3 trial.

Of the 242 patients in the RESET-RA study, all received the VNS device implant but were blinded as to whether the device was turned on. At 12 weeks, 35.2% of patients receiving daily stimulation achieved 20% improvement in American College of Rheumatology response criteria (ACR20) compared with 24.2% of those with an inactive device. The response was more pronounced among patients with exposure to only one prior b/tsDMARD. A greater proportion of patients in the overall treatment group also reached low disease activity or remission compared with those who did not receive stimulation. 

The research was presented as a late-breaking poster at the ACR 2024 Annual Meeting.

“This is a particularly tough-to-treat patient population, since the patients enrolled were considered refractory to biologic therapy,” said Elena Schiopu, MD, professor of medicine in the Division of Rheumatology and director of clinical trials at the Medical College of Georgia at Augusta University. More than one third of patients in the study had tried three or more b/tsDMARDs prior to the study. “I’m pretty excited about these results,” she added. Schiopu was a RESET-RA institutional principal investigator and enrolled two patients in the trial.

These positive results are a first for VNS treatment in rheumatic diseases. Previous studies demonstrating the potential therapeutic effect of this implant approach have largely been open-label, proof-of-concept, or pilot studies. Noninvasive, wearable stimulation devices have also shown promise in open-label studies; however, a sham-controlled trial published in 2023 showed that transcutaneous vagus nerve stimulation on the ear was no more effective than placebo. 

 

But How Does It Work?

The device, developed by SetPoint Medical in Valencia, California, is about the size of a multivitamin and implanted in an outpatient setting. During the 45-minute procedure, surgeons isolate the vagus nerve on the left side of the neck and place the nerve stimulator with a silicone positioning pod to hold it in place.

The device is programmed to deliver stimulation for 1 minute every day and needs charging for only 10 minutes once a week, which is done remotely with a necklace.

The device takes advantage of the vagus nerve’s anti-inflammatory properties, stimulating the nerve to help regulate an overactive immune system of someone with RA, explained David Chernoff, MD, Setpoint Medical’s chief medical officer. 

“We’re recapitulating what nature has developed over millions of years, which is the nexus between the brain and the immune system, which happens to be mediated by the vagus nerve,” he told Medscape Medical News. 

This novel VNS approach also does not have the same immunosuppressive safety concerns as drugs commonly used to treat RA, he said. 

“We’re able to adjust the amount of inflammation, but we don’t cause the host defense issues” that are present with some of these drugs, he continued.

SetPoint Medical’s pilot study of the device in 14 patients showed promising results. Five of 10 patients randomly assigned to active VNS over 12 weeks showed clinical improvements, measured by 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP) and the Clinical Disease Activity Index. In the remaining four patients who received sham stimulation — where the device was implanted but not activated — there were no clinical disease improvements.

 

RESET-RA Details

The most recent, much larger phase 3 study enrolled patients from 41 sites in the United States. Patients were on average 56 years old and had a body mass index of 30; 86% were women. A total of 39% had previously tried one b/tsDMARD, 22% had tried two, and 39% had tried three or more. Patients, on average, had 15 tender joints and 10 swollen joints. Patients discontinued their prior b/tsDMARD before the procedure and remained on conventional DMARDS during the trial, including methotrexate, hydroxychloroquine, and sulfasalazine.

The researchers randomly assigned patients 1:1 to active (treatment) or nonactive (control) stimulation. 

“The perception of stimulation varies from patient to patient, which itself is helpful in blinding as there is no expected perception of whether or how stimulation will be felt,” Chernoff explained. The 1-minute stimulation was scheduled in the early hours of the morning, when a patient typically would be asleep, he said.

Patients were excluded from the analysis if they were rescued by steroids or b/tsDMARDs through week 12. After week 12, the control group was switched to stimulation and efficacy was reassessed at week 24.

 

Higher ACR20 Response Rate, Lower Disease Activity

Beyond meeting the primary endpoint of ACR20 response, patients on the active stimulation group showed lower disease activity at week 12. Compared with 15.8% of patients in the control group, 27% of those in the treatment group achieved a DAS28-CRP ≤ 3.2. 

The active stimulation was particularly effective in patients who had experience with only one prior b/tsDMARD. In this subset of patients, 44.2% in the treatment group achieved ACR20 compared with 19.0% in the control group.

During this sham-controlled trial period, 13.1% of patients in the treatment group and 18.3% of patients in the control group reported an adverse event (AE) related to the procedure or device, most commonly vocal cord paresis or dysphonia. In the treatment group, 8.2% reported stimulation-related AEs, most commonly mild/moderate pain that was managed by adjusting the stimulation level. 

Serious adverse events (SAEs) were relatively rare, with four treatment-related SAEs across both study groups. No AEs led to study discontinuation through week 24.

The 12-week results mirror those of the initial Humira and Enbrel trials in the late 1990s and early 2000s, Schiopu said, although in those trials, the patients were naive to biologics, and some were naive to methotrexate. A more appropriate comparison, she said, would be biologic-experienced populations.

At week 24, the percentage of patients achieving ACR20 further increased to 51.5% in the treatment group and to 53.1% in the previous control group who were now crossed over to active stimulation. In this secondary period, patients could add any additional therapies like steroids or b/tsDMARDs. At 24 weeks, 81% of patients remained on stimulation without needing additional medication, beyond their continued background DMARDs. 

The results also show “a continuum of improvement over time,” Schiopu said, where response rates climbed through week 24. 

Schiopu is particularly excited about the potential to use this stimulation device in older patients, who have perhaps been on immunosuppressant drugs for decades. 

“Aside from being chronically immunosuppressed, their immune system is more tired [due to age],” she said. With VNS therapies like SetPoint’s, “we could offer [these patients] a lesser immunosuppressive alternative that is still immune-modular enough to manage their RA.”

Schiopu is a consultant for Johnson & Johnson and reported receiving research funding for serving as an institutional principal investigator for SetPoint, Galapagos, Johnson & Johnson, Boehringer Ingelheim, Lilly, argenx, EMD Serono, Priovant, Novartis, Bristol Myers Squibb, Zena Pharmaceuticals, and Horizon/Amgen.

 

A version of this article appeared on Medscape.com.

WASHINGTON — An implantable vagus nerve stimulation (VNS) device effectively treats moderate to severe rheumatoid arthritis (RA) in patients who had previously failed at least one biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD), according to results from a phase 3 trial.

Of the 242 patients in the RESET-RA study, all received the VNS device implant but were blinded as to whether the device was turned on. At 12 weeks, 35.2% of patients receiving daily stimulation achieved 20% improvement in American College of Rheumatology response criteria (ACR20) compared with 24.2% of those with an inactive device. The response was more pronounced among patients with exposure to only one prior b/tsDMARD. A greater proportion of patients in the overall treatment group also reached low disease activity or remission compared with those who did not receive stimulation. 

The research was presented as a late-breaking poster at the ACR 2024 Annual Meeting.

“This is a particularly tough-to-treat patient population, since the patients enrolled were considered refractory to biologic therapy,” said Elena Schiopu, MD, professor of medicine in the Division of Rheumatology and director of clinical trials at the Medical College of Georgia at Augusta University. More than one third of patients in the study had tried three or more b/tsDMARDs prior to the study. “I’m pretty excited about these results,” she added. Schiopu was a RESET-RA institutional principal investigator and enrolled two patients in the trial.

These positive results are a first for VNS treatment in rheumatic diseases. Previous studies demonstrating the potential therapeutic effect of this implant approach have largely been open-label, proof-of-concept, or pilot studies. Noninvasive, wearable stimulation devices have also shown promise in open-label studies; however, a sham-controlled trial published in 2023 showed that transcutaneous vagus nerve stimulation on the ear was no more effective than placebo. 

 

But How Does It Work?

The device, developed by SetPoint Medical in Valencia, California, is about the size of a multivitamin and implanted in an outpatient setting. During the 45-minute procedure, surgeons isolate the vagus nerve on the left side of the neck and place the nerve stimulator with a silicone positioning pod to hold it in place.

The device is programmed to deliver stimulation for 1 minute every day and needs charging for only 10 minutes once a week, which is done remotely with a necklace.

The device takes advantage of the vagus nerve’s anti-inflammatory properties, stimulating the nerve to help regulate an overactive immune system of someone with RA, explained David Chernoff, MD, Setpoint Medical’s chief medical officer. 

“We’re recapitulating what nature has developed over millions of years, which is the nexus between the brain and the immune system, which happens to be mediated by the vagus nerve,” he told Medscape Medical News. 

This novel VNS approach also does not have the same immunosuppressive safety concerns as drugs commonly used to treat RA, he said. 

“We’re able to adjust the amount of inflammation, but we don’t cause the host defense issues” that are present with some of these drugs, he continued.

SetPoint Medical’s pilot study of the device in 14 patients showed promising results. Five of 10 patients randomly assigned to active VNS over 12 weeks showed clinical improvements, measured by 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP) and the Clinical Disease Activity Index. In the remaining four patients who received sham stimulation — where the device was implanted but not activated — there were no clinical disease improvements.

 

RESET-RA Details

The most recent, much larger phase 3 study enrolled patients from 41 sites in the United States. Patients were on average 56 years old and had a body mass index of 30; 86% were women. A total of 39% had previously tried one b/tsDMARD, 22% had tried two, and 39% had tried three or more. Patients, on average, had 15 tender joints and 10 swollen joints. Patients discontinued their prior b/tsDMARD before the procedure and remained on conventional DMARDS during the trial, including methotrexate, hydroxychloroquine, and sulfasalazine.

The researchers randomly assigned patients 1:1 to active (treatment) or nonactive (control) stimulation. 

“The perception of stimulation varies from patient to patient, which itself is helpful in blinding as there is no expected perception of whether or how stimulation will be felt,” Chernoff explained. The 1-minute stimulation was scheduled in the early hours of the morning, when a patient typically would be asleep, he said.

Patients were excluded from the analysis if they were rescued by steroids or b/tsDMARDs through week 12. After week 12, the control group was switched to stimulation and efficacy was reassessed at week 24.

 

Higher ACR20 Response Rate, Lower Disease Activity

Beyond meeting the primary endpoint of ACR20 response, patients on the active stimulation group showed lower disease activity at week 12. Compared with 15.8% of patients in the control group, 27% of those in the treatment group achieved a DAS28-CRP ≤ 3.2. 

The active stimulation was particularly effective in patients who had experience with only one prior b/tsDMARD. In this subset of patients, 44.2% in the treatment group achieved ACR20 compared with 19.0% in the control group.

During this sham-controlled trial period, 13.1% of patients in the treatment group and 18.3% of patients in the control group reported an adverse event (AE) related to the procedure or device, most commonly vocal cord paresis or dysphonia. In the treatment group, 8.2% reported stimulation-related AEs, most commonly mild/moderate pain that was managed by adjusting the stimulation level. 

Serious adverse events (SAEs) were relatively rare, with four treatment-related SAEs across both study groups. No AEs led to study discontinuation through week 24.

The 12-week results mirror those of the initial Humira and Enbrel trials in the late 1990s and early 2000s, Schiopu said, although in those trials, the patients were naive to biologics, and some were naive to methotrexate. A more appropriate comparison, she said, would be biologic-experienced populations.

At week 24, the percentage of patients achieving ACR20 further increased to 51.5% in the treatment group and to 53.1% in the previous control group who were now crossed over to active stimulation. In this secondary period, patients could add any additional therapies like steroids or b/tsDMARDs. At 24 weeks, 81% of patients remained on stimulation without needing additional medication, beyond their continued background DMARDs. 

The results also show “a continuum of improvement over time,” Schiopu said, where response rates climbed through week 24. 

Schiopu is particularly excited about the potential to use this stimulation device in older patients, who have perhaps been on immunosuppressant drugs for decades. 

“Aside from being chronically immunosuppressed, their immune system is more tired [due to age],” she said. With VNS therapies like SetPoint’s, “we could offer [these patients] a lesser immunosuppressive alternative that is still immune-modular enough to manage their RA.”

Schiopu is a consultant for Johnson & Johnson and reported receiving research funding for serving as an institutional principal investigator for SetPoint, Galapagos, Johnson & Johnson, Boehringer Ingelheim, Lilly, argenx, EMD Serono, Priovant, Novartis, Bristol Myers Squibb, Zena Pharmaceuticals, and Horizon/Amgen.

 

A version of this article appeared on Medscape.com.

WASHINGTON — A diagnostic test to predict preeclampsia does not effectively rule in or out this pregnancy complication in women with systemic lupus erythematosus (SLE) and proteinuria, according to new research presented at the annual meeting of the American College of Rheumatology (ACR).

“If you have a patient who has proteinuria during pregnancy, I’m not sure we know what to do with this test,” said Megan Clowse, MD, MPH, associate professor of medicine and chief of the Division of Rheumatology and Immunology at Duke University School of Medicine in Durham, North Carolina. She led the research and presented the work.

The results “are probably a step in the right direction to understanding that we need more biochemical markers for differentiating preeclampsia [in this patient population],” Leanna Wise, MD, of the Keck School of Medicine at the University of Southern California, Los Angeles, said in an interview. She comoderated the session where the research was presented. “It exposed that we have a lot of gray areas in which we need to do more research.”

The test is a ratio of two biomarkers that measure spiral artery and placental health: Soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF). In the general population, a sFlt-1/PlGF ratio ≤ 38 effectively rules out the short-term risk for preeclampsia, whereas a ratio ≥ 85 is moderately predictive of preeclampsia. However, it was not known how this test would fare in pregnant women with SLE who are already at a higher risk for the complication.

To answer this question, Clowse and colleagues pulled patient data from an ongoing prospective registry of lupus pregnancies. The analysis included patients with a confirmed SLE diagnosis who had enrolled in the registry prior to 30 weeks’ gestation. All participants had provided a serum sample prior to 16 weeks’ gestation and had singleton pregnancies.

In an extensive chart review, preeclampsia was determined by a roundtable of six experts: Two rheumatologists, two maternal-fetal medicine doctors, and two nephrologists.

The analysis included 79 pregnancies, of which 30% developed preeclampsia. Nearly half (47%) of the participants identified as Black or African American. About 30% had a history of lupus nephritis, and half of these patients had active disease during their pregnancy. About half of the women reported that this was their first pregnancy, and an additional 17% of women reported a prior episode of preeclampsia. Most patients were on aspirin (92%) and hydroxychloroquine (87%), and another 43% were prescribed prednisone and 37% were taking azathioprine.

Researchers assessed whether a low sFlt-1/PlGF ratio (≤ 38) was associated with the absence of preeclampsia at 4- and 8-weeks post–blood draw, as well as during the entire pregnancy. They also tested if a high ratio (≥ 85) was associated with the development of preeclampsia within 4- and 8-weeks post–blood draw and through the entire pregnancy.

Across all pregnancies in the cohort, those with sFlt-1/PlGF ≤ 38 were unlikely to develop preeclampsia at 4 weeks post draw (negative predictive value [NPV], 98%) and 8 weeks post draw (NPV, 96%). Still, 20% of patients with this low ratio went on to develop preeclampsia at some point during their pregnancy.

Similar to the general population, sFlt-1/PlGF ≥ 85 was only moderately predictive of preeclampsia. Over half of all patients with this high ratio developed preeclampsia, but more than 40% did not.

Researchers also stratified patients by urine protein:creatinine ratio (UPCR) at the time of their rheumatology visit, defining proteinuria as a UPCR ≥ 300 mg/g.

In patients without proteinuria (n = 63), a low sFlt-1/PlGF ratio ruled out preeclampsia over the next 8 weeks, but a high sFlt-1/PlGF ratio was not usefully predictive of preeclampsia.

 

Low Ratio to Rule Out Preeclampsia ‘Reassuring’

The high reliability in ruling out preeclampsia in this subset of patients with a low sFlt-1/PlGF ratio is “reassuring,” Wise said, and suggests that these patients are “relatively safe moving forward,” given regular follow-up.

In the small group of patients with proteinuria (n = 16), 44% ultimately developed preeclampsia. One third of patients with sFlt-1/PlGF ≤ 38 developed preeclampsia in 8 weeks, and half experienced preeclampsia at some point during their pregnancy. Among the patients with sFlt-1:PlGF ≥ 85, 56% developed preeclampsia during their pregnancy.

“The negative predictive values are not really great, and the positive predictive values are not really very useful,” Clowse said. For a pregnant patient with proteinuria, “I don’t think that a high [ratio] is going to tell us that she definitely has preeclampsia today or tomorrow. I also am not convinced yet that a low [ratio] tells us that she’s out of the woods. So, I think we definitely need more research on what to do with this test in patients with proteinuria.”

Clowse is a consultant and has received research support/grants from GSK and UCB. She also reported consulting for AstraZeneca. Wise is a consultant for Aurinia Pharmaceuticals and has received honoraria from AstraZeneca, Aurinia Pharmaceuticals, and GSK.

A version of this article first appeared on Medscape.com.

WASHINGTON — A diagnostic test to predict preeclampsia does not effectively rule in or out this pregnancy complication in women with systemic lupus erythematosus (SLE) and proteinuria, according to new research presented at the annual meeting of the American College of Rheumatology (ACR).

“If you have a patient who has proteinuria during pregnancy, I’m not sure we know what to do with this test,” said Megan Clowse, MD, MPH, associate professor of medicine and chief of the Division of Rheumatology and Immunology at Duke University School of Medicine in Durham, North Carolina. She led the research and presented the work.

The results “are probably a step in the right direction to understanding that we need more biochemical markers for differentiating preeclampsia [in this patient population],” Leanna Wise, MD, of the Keck School of Medicine at the University of Southern California, Los Angeles, said in an interview. She comoderated the session where the research was presented. “It exposed that we have a lot of gray areas in which we need to do more research.”

The test is a ratio of two biomarkers that measure spiral artery and placental health: Soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF). In the general population, a sFlt-1/PlGF ratio ≤ 38 effectively rules out the short-term risk for preeclampsia, whereas a ratio ≥ 85 is moderately predictive of preeclampsia. However, it was not known how this test would fare in pregnant women with SLE who are already at a higher risk for the complication.

To answer this question, Clowse and colleagues pulled patient data from an ongoing prospective registry of lupus pregnancies. The analysis included patients with a confirmed SLE diagnosis who had enrolled in the registry prior to 30 weeks’ gestation. All participants had provided a serum sample prior to 16 weeks’ gestation and had singleton pregnancies.

In an extensive chart review, preeclampsia was determined by a roundtable of six experts: Two rheumatologists, two maternal-fetal medicine doctors, and two nephrologists.

The analysis included 79 pregnancies, of which 30% developed preeclampsia. Nearly half (47%) of the participants identified as Black or African American. About 30% had a history of lupus nephritis, and half of these patients had active disease during their pregnancy. About half of the women reported that this was their first pregnancy, and an additional 17% of women reported a prior episode of preeclampsia. Most patients were on aspirin (92%) and hydroxychloroquine (87%), and another 43% were prescribed prednisone and 37% were taking azathioprine.

Researchers assessed whether a low sFlt-1/PlGF ratio (≤ 38) was associated with the absence of preeclampsia at 4- and 8-weeks post–blood draw, as well as during the entire pregnancy. They also tested if a high ratio (≥ 85) was associated with the development of preeclampsia within 4- and 8-weeks post–blood draw and through the entire pregnancy.

Across all pregnancies in the cohort, those with sFlt-1/PlGF ≤ 38 were unlikely to develop preeclampsia at 4 weeks post draw (negative predictive value [NPV], 98%) and 8 weeks post draw (NPV, 96%). Still, 20% of patients with this low ratio went on to develop preeclampsia at some point during their pregnancy.

Similar to the general population, sFlt-1/PlGF ≥ 85 was only moderately predictive of preeclampsia. Over half of all patients with this high ratio developed preeclampsia, but more than 40% did not.

Researchers also stratified patients by urine protein:creatinine ratio (UPCR) at the time of their rheumatology visit, defining proteinuria as a UPCR ≥ 300 mg/g.

In patients without proteinuria (n = 63), a low sFlt-1/PlGF ratio ruled out preeclampsia over the next 8 weeks, but a high sFlt-1/PlGF ratio was not usefully predictive of preeclampsia.

 

Low Ratio to Rule Out Preeclampsia ‘Reassuring’

The high reliability in ruling out preeclampsia in this subset of patients with a low sFlt-1/PlGF ratio is “reassuring,” Wise said, and suggests that these patients are “relatively safe moving forward,” given regular follow-up.

In the small group of patients with proteinuria (n = 16), 44% ultimately developed preeclampsia. One third of patients with sFlt-1/PlGF ≤ 38 developed preeclampsia in 8 weeks, and half experienced preeclampsia at some point during their pregnancy. Among the patients with sFlt-1:PlGF ≥ 85, 56% developed preeclampsia during their pregnancy.

“The negative predictive values are not really great, and the positive predictive values are not really very useful,” Clowse said. For a pregnant patient with proteinuria, “I don’t think that a high [ratio] is going to tell us that she definitely has preeclampsia today or tomorrow. I also am not convinced yet that a low [ratio] tells us that she’s out of the woods. So, I think we definitely need more research on what to do with this test in patients with proteinuria.”

Clowse is a consultant and has received research support/grants from GSK and UCB. She also reported consulting for AstraZeneca. Wise is a consultant for Aurinia Pharmaceuticals and has received honoraria from AstraZeneca, Aurinia Pharmaceuticals, and GSK.

A version of this article first appeared on Medscape.com.

WASHINGTON — A diagnostic test to predict preeclampsia does not effectively rule in or out this pregnancy complication in women with systemic lupus erythematosus (SLE) and proteinuria, according to new research presented at the annual meeting of the American College of Rheumatology (ACR).

“If you have a patient who has proteinuria during pregnancy, I’m not sure we know what to do with this test,” said Megan Clowse, MD, MPH, associate professor of medicine and chief of the Division of Rheumatology and Immunology at Duke University School of Medicine in Durham, North Carolina. She led the research and presented the work.

The results “are probably a step in the right direction to understanding that we need more biochemical markers for differentiating preeclampsia [in this patient population],” Leanna Wise, MD, of the Keck School of Medicine at the University of Southern California, Los Angeles, said in an interview. She comoderated the session where the research was presented. “It exposed that we have a lot of gray areas in which we need to do more research.”

The test is a ratio of two biomarkers that measure spiral artery and placental health: Soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF). In the general population, a sFlt-1/PlGF ratio ≤ 38 effectively rules out the short-term risk for preeclampsia, whereas a ratio ≥ 85 is moderately predictive of preeclampsia. However, it was not known how this test would fare in pregnant women with SLE who are already at a higher risk for the complication.

To answer this question, Clowse and colleagues pulled patient data from an ongoing prospective registry of lupus pregnancies. The analysis included patients with a confirmed SLE diagnosis who had enrolled in the registry prior to 30 weeks’ gestation. All participants had provided a serum sample prior to 16 weeks’ gestation and had singleton pregnancies.

In an extensive chart review, preeclampsia was determined by a roundtable of six experts: Two rheumatologists, two maternal-fetal medicine doctors, and two nephrologists.

The analysis included 79 pregnancies, of which 30% developed preeclampsia. Nearly half (47%) of the participants identified as Black or African American. About 30% had a history of lupus nephritis, and half of these patients had active disease during their pregnancy. About half of the women reported that this was their first pregnancy, and an additional 17% of women reported a prior episode of preeclampsia. Most patients were on aspirin (92%) and hydroxychloroquine (87%), and another 43% were prescribed prednisone and 37% were taking azathioprine.

Researchers assessed whether a low sFlt-1/PlGF ratio (≤ 38) was associated with the absence of preeclampsia at 4- and 8-weeks post–blood draw, as well as during the entire pregnancy. They also tested if a high ratio (≥ 85) was associated with the development of preeclampsia within 4- and 8-weeks post–blood draw and through the entire pregnancy.

Across all pregnancies in the cohort, those with sFlt-1/PlGF ≤ 38 were unlikely to develop preeclampsia at 4 weeks post draw (negative predictive value [NPV], 98%) and 8 weeks post draw (NPV, 96%). Still, 20% of patients with this low ratio went on to develop preeclampsia at some point during their pregnancy.

Similar to the general population, sFlt-1/PlGF ≥ 85 was only moderately predictive of preeclampsia. Over half of all patients with this high ratio developed preeclampsia, but more than 40% did not.

Researchers also stratified patients by urine protein:creatinine ratio (UPCR) at the time of their rheumatology visit, defining proteinuria as a UPCR ≥ 300 mg/g.

In patients without proteinuria (n = 63), a low sFlt-1/PlGF ratio ruled out preeclampsia over the next 8 weeks, but a high sFlt-1/PlGF ratio was not usefully predictive of preeclampsia.

 

Low Ratio to Rule Out Preeclampsia ‘Reassuring’

The high reliability in ruling out preeclampsia in this subset of patients with a low sFlt-1/PlGF ratio is “reassuring,” Wise said, and suggests that these patients are “relatively safe moving forward,” given regular follow-up.

In the small group of patients with proteinuria (n = 16), 44% ultimately developed preeclampsia. One third of patients with sFlt-1/PlGF ≤ 38 developed preeclampsia in 8 weeks, and half experienced preeclampsia at some point during their pregnancy. Among the patients with sFlt-1:PlGF ≥ 85, 56% developed preeclampsia during their pregnancy.

“The negative predictive values are not really great, and the positive predictive values are not really very useful,” Clowse said. For a pregnant patient with proteinuria, “I don’t think that a high [ratio] is going to tell us that she definitely has preeclampsia today or tomorrow. I also am not convinced yet that a low [ratio] tells us that she’s out of the woods. So, I think we definitely need more research on what to do with this test in patients with proteinuria.”

Clowse is a consultant and has received research support/grants from GSK and UCB. She also reported consulting for AstraZeneca. Wise is a consultant for Aurinia Pharmaceuticals and has received honoraria from AstraZeneca, Aurinia Pharmaceuticals, and GSK.

A version of this article first appeared on Medscape.com.

WASHINGTON — There is no benefit to interrupting treatment with many of the available targeted synthetic or biologic disease-modifying antirheumatic drugs for rheumatoid arthritis (RA) or spondyloarthritis (SpA) at the time of a repeat COVID-19 vaccine dose, new research found.

In the multicenter, randomized controlled COVID Vaccine Response (COVER) trial of 577 patients with RA or SpA taking either abatacept, Janus kinase (JAK) inhibitors, interleukin (IL)–17 inhibitors, or tumor necrosis factor (TNF) inhibitors, holding those drugs for 2 weeks at the time of COVID-19 vaccination supplemental doses didn’t improve antibody response to the vaccine but did lead to disease flares. Most participants had significant antibody responses to the vaccine, regardless of whether their medication had been held or continued, Jeffrey R. Curtis, MD, the Harbert-Ball Professor of Medicine, Epidemiology, and Computer Science at the University of Alabama at Birmingham, reported at the annual meeting of the American College of Rheumatology (ACR).

Guidelines issued by ACR in 2023 recommended holding abatacept for the COVID vaccine but said that “the task force failed to reach consensus” on whether or not to temporarily interrupt the other medications following primary vaccination or supplemental/booster dosing.

Curtis, who was an author on those guidelines, said in an interview, “to date, we haven’t known whether it might be a good idea to hold certain drugs at the time patients receive their next dose of the COVID vaccine. ... That’s because without direct evidence, you have people trading opinions based on extrapolated data.” 

The inability to measure cell-mediated immunity and only humoral (ie, antibody-based) immunity is a limitation in COVER. “Nevertheless, based on what we know now, it isn’t advisable to hold any of the four drug classes that we studied at the time patients receive their next COVID vaccine dose. This finding is in contrast to data from a different trial showing that holding methotrexate for 2 weeks does appear to help in response to COVID-19 vaccination, as well as influenza vaccine,” Curtis said.

Asked to comment, session moderator Elena Myasoedova, MD, PhD, consultant rheumatologist and director of the Inflammatory Arthritis Clinic at the Mayo Clinic, Rochester, Minnesota, said in an interview: “This has been an area of clinical uncertainty. It raises a lot of questions from patients and from physicians alike as to whether or not to hold the medication because the implications are flares, and that’s impactful for patients. Patients care about their RA status and how it is controlled, and if there is no difference, then there is no reason to change the medication regimen.”

 

To Hold or Not to Hold: COVER Shows It Makes Little Difference to Vaccine Response

In COVER, 128 patients were taking abatacept, 96 IL-17 inhibitors, 237 JAK inhibitors, and 116 TNF inhibitors. The study was conducted within 30 sites of the Excellence Network in Rheumatology, a rheumatology practice–based research network launched in 2021. Participants were identified and enrolled at clinic visits immediately prior to receiving their COVID-19 boosters (in routine settings).

All had previously received two or more doses of the mRNA vaccines made by Pfizer or Moderna. Blood was drawn, and they were randomized 1:1 to either continue or hold their disease medication for 2 weeks following the booster. Blood was collected again at 6 weeks post vaccine.

Anti–receptor-binding domain (RBD) IgG antibody titers increased significantly in all drug categories across both study arms, with no differences between the hold vs continue medication groups, even after adjustments for age, sex, body mass index, methotrexate use, steroid use, and time from booster to measurement. All groups also showed increases in geometric mean fold rise of more than 3%.

Subgroup analyses showed no major differences between antibody responses in the hold vs continue groups. The anti-RBD IgG response was lower for abatacept and JAK inhibitors than for the other two drugs, but there was still no significant benefit to holding them for 2 weeks post vaccination.

 

Holding Drugs Leads to Disease Flares

On the flip side, there were significant differences between the two groups in their responses to the question: “Did you experience any flare or worsening of your autoimmune disease following your recent COVID-19 booster dose?” Overall, 27% of the hold group responded that they had, compared with just 13% of the continue group (P < .05). This difference was greatest in the JAK inhibitor group (33% vs 9%; P < .05).

Among those reporting flares or worsening disease, both the severity and the duration of the flares were about the same. “Interestingly, the duration is beyond a week for the majority of patients. The reason that’s important is, any symptoms that are so-called flare might simply be reactogenicity symptoms, and that might be confused for flare or disease worsening, but you see that a majority of patients actually have those symptoms extending beyond the week. Most of them are worsening in arthritis, as you might expect,” Curtis said in his presentation.

Asked what they did about the flare, only a minority of patients reported contacting a healthcare provider. In all, 68% of the hold group and 78% of the continue group took no action. That’s good in the sense that most of the flares weren’t severe, but it has implications for research, Curtis pointed out.

“A lot of times in the vaccine literature, people do retrospective chart review by looking to see what the doctor said as to whether the patient had a flare. And what this would tell you is patients may be reporting a lot of flares that their doctor doesn’t know anything about. So if you really want to know whether people are having a flare, even a mild flare, you really have to collect prospective data.”

 

COVID is Not the Last Pandemic

“These results are reassuring, although I think we need a bit more data on abatacept,” Myasoedova said, adding, “I was also interested in the outcomes, such as severe infections, that actually happened to these patients. What we see in the labs in their immune response is one thing, but then also important is what actually evolves in terms of the outcomes, especially with abatacept.”

Overall, she said, “I think it’s reassuring and definitely informs clinical practice going forward. But then probably we’ll learn more. What we’re hearing is COVID is not the last pandemic.”

The COVER trial receives support from AbbVie, BMS, Eli Lilly, Novartis, and Pfizer. Curtis has received research grants and consulting fees from AbbVie, Amgen, BMS, GSK, Eli Lilly, Novartis, Pfizer, Sanofi, and UCB. Myasoedova has no disclosures.

A version of this article first appeared on Medscape.com.

WASHINGTON — There is no benefit to interrupting treatment with many of the available targeted synthetic or biologic disease-modifying antirheumatic drugs for rheumatoid arthritis (RA) or spondyloarthritis (SpA) at the time of a repeat COVID-19 vaccine dose, new research found.

In the multicenter, randomized controlled COVID Vaccine Response (COVER) trial of 577 patients with RA or SpA taking either abatacept, Janus kinase (JAK) inhibitors, interleukin (IL)–17 inhibitors, or tumor necrosis factor (TNF) inhibitors, holding those drugs for 2 weeks at the time of COVID-19 vaccination supplemental doses didn’t improve antibody response to the vaccine but did lead to disease flares. Most participants had significant antibody responses to the vaccine, regardless of whether their medication had been held or continued, Jeffrey R. Curtis, MD, the Harbert-Ball Professor of Medicine, Epidemiology, and Computer Science at the University of Alabama at Birmingham, reported at the annual meeting of the American College of Rheumatology (ACR).

Guidelines issued by ACR in 2023 recommended holding abatacept for the COVID vaccine but said that “the task force failed to reach consensus” on whether or not to temporarily interrupt the other medications following primary vaccination or supplemental/booster dosing.

Curtis, who was an author on those guidelines, said in an interview, “to date, we haven’t known whether it might be a good idea to hold certain drugs at the time patients receive their next dose of the COVID vaccine. ... That’s because without direct evidence, you have people trading opinions based on extrapolated data.” 

The inability to measure cell-mediated immunity and only humoral (ie, antibody-based) immunity is a limitation in COVER. “Nevertheless, based on what we know now, it isn’t advisable to hold any of the four drug classes that we studied at the time patients receive their next COVID vaccine dose. This finding is in contrast to data from a different trial showing that holding methotrexate for 2 weeks does appear to help in response to COVID-19 vaccination, as well as influenza vaccine,” Curtis said.

Asked to comment, session moderator Elena Myasoedova, MD, PhD, consultant rheumatologist and director of the Inflammatory Arthritis Clinic at the Mayo Clinic, Rochester, Minnesota, said in an interview: “This has been an area of clinical uncertainty. It raises a lot of questions from patients and from physicians alike as to whether or not to hold the medication because the implications are flares, and that’s impactful for patients. Patients care about their RA status and how it is controlled, and if there is no difference, then there is no reason to change the medication regimen.”

 

To Hold or Not to Hold: COVER Shows It Makes Little Difference to Vaccine Response

In COVER, 128 patients were taking abatacept, 96 IL-17 inhibitors, 237 JAK inhibitors, and 116 TNF inhibitors. The study was conducted within 30 sites of the Excellence Network in Rheumatology, a rheumatology practice–based research network launched in 2021. Participants were identified and enrolled at clinic visits immediately prior to receiving their COVID-19 boosters (in routine settings).

All had previously received two or more doses of the mRNA vaccines made by Pfizer or Moderna. Blood was drawn, and they were randomized 1:1 to either continue or hold their disease medication for 2 weeks following the booster. Blood was collected again at 6 weeks post vaccine.

Anti–receptor-binding domain (RBD) IgG antibody titers increased significantly in all drug categories across both study arms, with no differences between the hold vs continue medication groups, even after adjustments for age, sex, body mass index, methotrexate use, steroid use, and time from booster to measurement. All groups also showed increases in geometric mean fold rise of more than 3%.

Subgroup analyses showed no major differences between antibody responses in the hold vs continue groups. The anti-RBD IgG response was lower for abatacept and JAK inhibitors than for the other two drugs, but there was still no significant benefit to holding them for 2 weeks post vaccination.

 

Holding Drugs Leads to Disease Flares

On the flip side, there were significant differences between the two groups in their responses to the question: “Did you experience any flare or worsening of your autoimmune disease following your recent COVID-19 booster dose?” Overall, 27% of the hold group responded that they had, compared with just 13% of the continue group (P < .05). This difference was greatest in the JAK inhibitor group (33% vs 9%; P < .05).

Among those reporting flares or worsening disease, both the severity and the duration of the flares were about the same. “Interestingly, the duration is beyond a week for the majority of patients. The reason that’s important is, any symptoms that are so-called flare might simply be reactogenicity symptoms, and that might be confused for flare or disease worsening, but you see that a majority of patients actually have those symptoms extending beyond the week. Most of them are worsening in arthritis, as you might expect,” Curtis said in his presentation.

Asked what they did about the flare, only a minority of patients reported contacting a healthcare provider. In all, 68% of the hold group and 78% of the continue group took no action. That’s good in the sense that most of the flares weren’t severe, but it has implications for research, Curtis pointed out.

“A lot of times in the vaccine literature, people do retrospective chart review by looking to see what the doctor said as to whether the patient had a flare. And what this would tell you is patients may be reporting a lot of flares that their doctor doesn’t know anything about. So if you really want to know whether people are having a flare, even a mild flare, you really have to collect prospective data.”

 

COVID is Not the Last Pandemic

“These results are reassuring, although I think we need a bit more data on abatacept,” Myasoedova said, adding, “I was also interested in the outcomes, such as severe infections, that actually happened to these patients. What we see in the labs in their immune response is one thing, but then also important is what actually evolves in terms of the outcomes, especially with abatacept.”

Overall, she said, “I think it’s reassuring and definitely informs clinical practice going forward. But then probably we’ll learn more. What we’re hearing is COVID is not the last pandemic.”

The COVER trial receives support from AbbVie, BMS, Eli Lilly, Novartis, and Pfizer. Curtis has received research grants and consulting fees from AbbVie, Amgen, BMS, GSK, Eli Lilly, Novartis, Pfizer, Sanofi, and UCB. Myasoedova has no disclosures.

A version of this article first appeared on Medscape.com.

WASHINGTON — There is no benefit to interrupting treatment with many of the available targeted synthetic or biologic disease-modifying antirheumatic drugs for rheumatoid arthritis (RA) or spondyloarthritis (SpA) at the time of a repeat COVID-19 vaccine dose, new research found.

In the multicenter, randomized controlled COVID Vaccine Response (COVER) trial of 577 patients with RA or SpA taking either abatacept, Janus kinase (JAK) inhibitors, interleukin (IL)–17 inhibitors, or tumor necrosis factor (TNF) inhibitors, holding those drugs for 2 weeks at the time of COVID-19 vaccination supplemental doses didn’t improve antibody response to the vaccine but did lead to disease flares. Most participants had significant antibody responses to the vaccine, regardless of whether their medication had been held or continued, Jeffrey R. Curtis, MD, the Harbert-Ball Professor of Medicine, Epidemiology, and Computer Science at the University of Alabama at Birmingham, reported at the annual meeting of the American College of Rheumatology (ACR).

Guidelines issued by ACR in 2023 recommended holding abatacept for the COVID vaccine but said that “the task force failed to reach consensus” on whether or not to temporarily interrupt the other medications following primary vaccination or supplemental/booster dosing.

Curtis, who was an author on those guidelines, said in an interview, “to date, we haven’t known whether it might be a good idea to hold certain drugs at the time patients receive their next dose of the COVID vaccine. ... That’s because without direct evidence, you have people trading opinions based on extrapolated data.” 

The inability to measure cell-mediated immunity and only humoral (ie, antibody-based) immunity is a limitation in COVER. “Nevertheless, based on what we know now, it isn’t advisable to hold any of the four drug classes that we studied at the time patients receive their next COVID vaccine dose. This finding is in contrast to data from a different trial showing that holding methotrexate for 2 weeks does appear to help in response to COVID-19 vaccination, as well as influenza vaccine,” Curtis said.

Asked to comment, session moderator Elena Myasoedova, MD, PhD, consultant rheumatologist and director of the Inflammatory Arthritis Clinic at the Mayo Clinic, Rochester, Minnesota, said in an interview: “This has been an area of clinical uncertainty. It raises a lot of questions from patients and from physicians alike as to whether or not to hold the medication because the implications are flares, and that’s impactful for patients. Patients care about their RA status and how it is controlled, and if there is no difference, then there is no reason to change the medication regimen.”

 

To Hold or Not to Hold: COVER Shows It Makes Little Difference to Vaccine Response

In COVER, 128 patients were taking abatacept, 96 IL-17 inhibitors, 237 JAK inhibitors, and 116 TNF inhibitors. The study was conducted within 30 sites of the Excellence Network in Rheumatology, a rheumatology practice–based research network launched in 2021. Participants were identified and enrolled at clinic visits immediately prior to receiving their COVID-19 boosters (in routine settings).

All had previously received two or more doses of the mRNA vaccines made by Pfizer or Moderna. Blood was drawn, and they were randomized 1:1 to either continue or hold their disease medication for 2 weeks following the booster. Blood was collected again at 6 weeks post vaccine.

Anti–receptor-binding domain (RBD) IgG antibody titers increased significantly in all drug categories across both study arms, with no differences between the hold vs continue medication groups, even after adjustments for age, sex, body mass index, methotrexate use, steroid use, and time from booster to measurement. All groups also showed increases in geometric mean fold rise of more than 3%.

Subgroup analyses showed no major differences between antibody responses in the hold vs continue groups. The anti-RBD IgG response was lower for abatacept and JAK inhibitors than for the other two drugs, but there was still no significant benefit to holding them for 2 weeks post vaccination.

 

Holding Drugs Leads to Disease Flares

On the flip side, there were significant differences between the two groups in their responses to the question: “Did you experience any flare or worsening of your autoimmune disease following your recent COVID-19 booster dose?” Overall, 27% of the hold group responded that they had, compared with just 13% of the continue group (P < .05). This difference was greatest in the JAK inhibitor group (33% vs 9%; P < .05).

Among those reporting flares or worsening disease, both the severity and the duration of the flares were about the same. “Interestingly, the duration is beyond a week for the majority of patients. The reason that’s important is, any symptoms that are so-called flare might simply be reactogenicity symptoms, and that might be confused for flare or disease worsening, but you see that a majority of patients actually have those symptoms extending beyond the week. Most of them are worsening in arthritis, as you might expect,” Curtis said in his presentation.

Asked what they did about the flare, only a minority of patients reported contacting a healthcare provider. In all, 68% of the hold group and 78% of the continue group took no action. That’s good in the sense that most of the flares weren’t severe, but it has implications for research, Curtis pointed out.

“A lot of times in the vaccine literature, people do retrospective chart review by looking to see what the doctor said as to whether the patient had a flare. And what this would tell you is patients may be reporting a lot of flares that their doctor doesn’t know anything about. So if you really want to know whether people are having a flare, even a mild flare, you really have to collect prospective data.”

 

COVID is Not the Last Pandemic

“These results are reassuring, although I think we need a bit more data on abatacept,” Myasoedova said, adding, “I was also interested in the outcomes, such as severe infections, that actually happened to these patients. What we see in the labs in their immune response is one thing, but then also important is what actually evolves in terms of the outcomes, especially with abatacept.”

Overall, she said, “I think it’s reassuring and definitely informs clinical practice going forward. But then probably we’ll learn more. What we’re hearing is COVID is not the last pandemic.”

The COVER trial receives support from AbbVie, BMS, Eli Lilly, Novartis, and Pfizer. Curtis has received research grants and consulting fees from AbbVie, Amgen, BMS, GSK, Eli Lilly, Novartis, Pfizer, Sanofi, and UCB. Myasoedova has no disclosures.

A version of this article first appeared on Medscape.com.

WASHINGTON — Women with rheumatoid arthritis (RA) experience improved fertility when treated using a treat-to-target (T2T) approach aimed at remission, according to a new research presented at the annual meeting of the American College of Rheumatology.

In the study, more than half the women following this T2T approach were able to conceive within 3 months, which is “nearly equal to the general population,” said presenter and senior author Radboud Dolhain, MD, PhD, who heads the Department of Rheumatology at Erasmus University Medical Center in Rotterdam, the Netherlands.

Compared with 10%-15% of the general population, as many as 42% of patients with RA are not able to get pregnant within 1 year of unprotected intercourse.

“For people who are thinking about pregnancy or want to plan for pregnancy, talking with them about the importance of making sure their RA is well-treated is an essential aspect,” said Mehret Birru Talabi, MD, PhD, director of the Women’s and Reproductive Health Rheumatology Clinic at the University of Pittsburgh Medical Center in Pennsylvania. She was not involved with the research.

“This is a nice, relatively large study that’s demonstrating [that] if you actually treat the patient and treat them effectively, their time to pregnancy is lower,” she said.

 

Study Details

The analysis compared time to pregnancy between two cohorts of women with RA who aimed to become pregnant. Women were, on average, around 32 years old in both groups, and nearly 60% had not been pregnant before.

The first cohort was part of the Pregnancy-Induced Amelioration of RA (PARA) study, conducted by Erasmus University Medical Center from 2002 to 2010, in which patients were treated by their own rheumatologists with standard of care at the time. Of the 245 women included, 36% were on no medication, and one fourth were taking nonsteroidal anti-inflammatory drugs (NSAIDs). One third of patients were prescribed sulfasalazine, 6% were on hydroxychloroquine, and 4% were prescribed a tumor necrosis factor (TNF) inhibitor. Of the PARA patients prescribed prednisone, about half used a dose > 7.5 mg/d.

The second cohort was part of the Preconception Counseling in Active RA (PreCARA) study, conducted at Erasmus University Medical Center from 2012 to 2023. PreCARA patients were treated with the T2T approach aimed at remission/low disease activity and avoiding use of NSAIDs and high-dose prednisone (> 7.5 mg/d). Of the 215 women in the cohort, 69% were on sulfasalazine, 65% were on hydroxychloroquine, 53% were taking a TNF inhibitor, 45% took prednisone, and 13% took NSAIDs. For patients prescribed prednisone, 75% used a daily dose ≤ 7.5 mg/d. Only six patients were not taking any medication.

In the preconception period, the median Disease Activity Score in 28 joints using C-reactive protein was 2.33 in the PreCARA cohort and 3.84 in the PARA cohort.

The median time to pregnancy was 84 days in the PreCARA cohort, compared with 196 days in the PARA cohort. Compared with 42% of women in the PARA cohort, less than a quarter of women in the PreCARA cohort did not conceive within 1 year of trying. There was no difference between the two groups in the use of assisted reproductive techniques.

In an additional analysis, Dolhain and colleagues found that time to pregnancy in the PreCARA cohort was most associated with maternal age and nulliparity.

“You also will find [this association] in every cohort in time to pregnancy, and it underscores the robustness of our data,” Dolhain said. “We didn’t find any association [with time to pregnancy] anymore with disease activity, the use of NSAIDs, and the use of prednisone.”

 

Study ‘Will Make Patients Feel More Confident in Their Decisions’

Discussions about continuing medication before and during pregnancy can be a “tension point” for some patients, Talabi said, and these types of studies provide further evidence to reassure patients that this approach can help them reach their reproductive goals.

The study is “very clinically translatable, where you can show [patients] the benefit of continuing their medications” in the preconception period and during pregnancy, added Catherine Sims, MD, a rheumatologist at Duke Health in Durham, North Carolina, who is focused on reproductive rheumatology and preventive health.

“What we try to drive home is that the health of the mother directly translates to the health of the pregnancy and that includes medications, and that is okay because now we have shown that pregnancies are safe while taking these medications,” she said. “I think [this study] will make patients feel more confident in their decisions, which is a big, important piece of it.”

Sims is a consultant for Amgen and conducted research funded by GlaxoSmithKline. Dolhain and Talabi had no relevant disclosures.

A version of this article first appeared on Medscape.com.

WASHINGTON — Women with rheumatoid arthritis (RA) experience improved fertility when treated using a treat-to-target (T2T) approach aimed at remission, according to a new research presented at the annual meeting of the American College of Rheumatology.

In the study, more than half the women following this T2T approach were able to conceive within 3 months, which is “nearly equal to the general population,” said presenter and senior author Radboud Dolhain, MD, PhD, who heads the Department of Rheumatology at Erasmus University Medical Center in Rotterdam, the Netherlands.

Compared with 10%-15% of the general population, as many as 42% of patients with RA are not able to get pregnant within 1 year of unprotected intercourse.

“For people who are thinking about pregnancy or want to plan for pregnancy, talking with them about the importance of making sure their RA is well-treated is an essential aspect,” said Mehret Birru Talabi, MD, PhD, director of the Women’s and Reproductive Health Rheumatology Clinic at the University of Pittsburgh Medical Center in Pennsylvania. She was not involved with the research.

“This is a nice, relatively large study that’s demonstrating [that] if you actually treat the patient and treat them effectively, their time to pregnancy is lower,” she said.

 

Study Details

The analysis compared time to pregnancy between two cohorts of women with RA who aimed to become pregnant. Women were, on average, around 32 years old in both groups, and nearly 60% had not been pregnant before.

The first cohort was part of the Pregnancy-Induced Amelioration of RA (PARA) study, conducted by Erasmus University Medical Center from 2002 to 2010, in which patients were treated by their own rheumatologists with standard of care at the time. Of the 245 women included, 36% were on no medication, and one fourth were taking nonsteroidal anti-inflammatory drugs (NSAIDs). One third of patients were prescribed sulfasalazine, 6% were on hydroxychloroquine, and 4% were prescribed a tumor necrosis factor (TNF) inhibitor. Of the PARA patients prescribed prednisone, about half used a dose > 7.5 mg/d.

The second cohort was part of the Preconception Counseling in Active RA (PreCARA) study, conducted at Erasmus University Medical Center from 2012 to 2023. PreCARA patients were treated with the T2T approach aimed at remission/low disease activity and avoiding use of NSAIDs and high-dose prednisone (> 7.5 mg/d). Of the 215 women in the cohort, 69% were on sulfasalazine, 65% were on hydroxychloroquine, 53% were taking a TNF inhibitor, 45% took prednisone, and 13% took NSAIDs. For patients prescribed prednisone, 75% used a daily dose ≤ 7.5 mg/d. Only six patients were not taking any medication.

In the preconception period, the median Disease Activity Score in 28 joints using C-reactive protein was 2.33 in the PreCARA cohort and 3.84 in the PARA cohort.

The median time to pregnancy was 84 days in the PreCARA cohort, compared with 196 days in the PARA cohort. Compared with 42% of women in the PARA cohort, less than a quarter of women in the PreCARA cohort did not conceive within 1 year of trying. There was no difference between the two groups in the use of assisted reproductive techniques.

In an additional analysis, Dolhain and colleagues found that time to pregnancy in the PreCARA cohort was most associated with maternal age and nulliparity.

“You also will find [this association] in every cohort in time to pregnancy, and it underscores the robustness of our data,” Dolhain said. “We didn’t find any association [with time to pregnancy] anymore with disease activity, the use of NSAIDs, and the use of prednisone.”

 

Study ‘Will Make Patients Feel More Confident in Their Decisions’

Discussions about continuing medication before and during pregnancy can be a “tension point” for some patients, Talabi said, and these types of studies provide further evidence to reassure patients that this approach can help them reach their reproductive goals.

The study is “very clinically translatable, where you can show [patients] the benefit of continuing their medications” in the preconception period and during pregnancy, added Catherine Sims, MD, a rheumatologist at Duke Health in Durham, North Carolina, who is focused on reproductive rheumatology and preventive health.

“What we try to drive home is that the health of the mother directly translates to the health of the pregnancy and that includes medications, and that is okay because now we have shown that pregnancies are safe while taking these medications,” she said. “I think [this study] will make patients feel more confident in their decisions, which is a big, important piece of it.”

Sims is a consultant for Amgen and conducted research funded by GlaxoSmithKline. Dolhain and Talabi had no relevant disclosures.

A version of this article first appeared on Medscape.com.

WASHINGTON — Women with rheumatoid arthritis (RA) experience improved fertility when treated using a treat-to-target (T2T) approach aimed at remission, according to a new research presented at the annual meeting of the American College of Rheumatology.

In the study, more than half the women following this T2T approach were able to conceive within 3 months, which is “nearly equal to the general population,” said presenter and senior author Radboud Dolhain, MD, PhD, who heads the Department of Rheumatology at Erasmus University Medical Center in Rotterdam, the Netherlands.

Compared with 10%-15% of the general population, as many as 42% of patients with RA are not able to get pregnant within 1 year of unprotected intercourse.

“For people who are thinking about pregnancy or want to plan for pregnancy, talking with them about the importance of making sure their RA is well-treated is an essential aspect,” said Mehret Birru Talabi, MD, PhD, director of the Women’s and Reproductive Health Rheumatology Clinic at the University of Pittsburgh Medical Center in Pennsylvania. She was not involved with the research.

“This is a nice, relatively large study that’s demonstrating [that] if you actually treat the patient and treat them effectively, their time to pregnancy is lower,” she said.

 

Study Details

The analysis compared time to pregnancy between two cohorts of women with RA who aimed to become pregnant. Women were, on average, around 32 years old in both groups, and nearly 60% had not been pregnant before.

The first cohort was part of the Pregnancy-Induced Amelioration of RA (PARA) study, conducted by Erasmus University Medical Center from 2002 to 2010, in which patients were treated by their own rheumatologists with standard of care at the time. Of the 245 women included, 36% were on no medication, and one fourth were taking nonsteroidal anti-inflammatory drugs (NSAIDs). One third of patients were prescribed sulfasalazine, 6% were on hydroxychloroquine, and 4% were prescribed a tumor necrosis factor (TNF) inhibitor. Of the PARA patients prescribed prednisone, about half used a dose > 7.5 mg/d.

The second cohort was part of the Preconception Counseling in Active RA (PreCARA) study, conducted at Erasmus University Medical Center from 2012 to 2023. PreCARA patients were treated with the T2T approach aimed at remission/low disease activity and avoiding use of NSAIDs and high-dose prednisone (> 7.5 mg/d). Of the 215 women in the cohort, 69% were on sulfasalazine, 65% were on hydroxychloroquine, 53% were taking a TNF inhibitor, 45% took prednisone, and 13% took NSAIDs. For patients prescribed prednisone, 75% used a daily dose ≤ 7.5 mg/d. Only six patients were not taking any medication.

In the preconception period, the median Disease Activity Score in 28 joints using C-reactive protein was 2.33 in the PreCARA cohort and 3.84 in the PARA cohort.

The median time to pregnancy was 84 days in the PreCARA cohort, compared with 196 days in the PARA cohort. Compared with 42% of women in the PARA cohort, less than a quarter of women in the PreCARA cohort did not conceive within 1 year of trying. There was no difference between the two groups in the use of assisted reproductive techniques.

In an additional analysis, Dolhain and colleagues found that time to pregnancy in the PreCARA cohort was most associated with maternal age and nulliparity.

“You also will find [this association] in every cohort in time to pregnancy, and it underscores the robustness of our data,” Dolhain said. “We didn’t find any association [with time to pregnancy] anymore with disease activity, the use of NSAIDs, and the use of prednisone.”

 

Study ‘Will Make Patients Feel More Confident in Their Decisions’

Discussions about continuing medication before and during pregnancy can be a “tension point” for some patients, Talabi said, and these types of studies provide further evidence to reassure patients that this approach can help them reach their reproductive goals.

The study is “very clinically translatable, where you can show [patients] the benefit of continuing their medications” in the preconception period and during pregnancy, added Catherine Sims, MD, a rheumatologist at Duke Health in Durham, North Carolina, who is focused on reproductive rheumatology and preventive health.

“What we try to drive home is that the health of the mother directly translates to the health of the pregnancy and that includes medications, and that is okay because now we have shown that pregnancies are safe while taking these medications,” she said. “I think [this study] will make patients feel more confident in their decisions, which is a big, important piece of it.”

Sims is a consultant for Amgen and conducted research funded by GlaxoSmithKline. Dolhain and Talabi had no relevant disclosures.

A version of this article first appeared on Medscape.com.

WASHINGTON — Use of sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduced the need for urate-lowering therapy (ULT) and gout flare therapies in people who had both type 2 diabetes (T2D) and gout, new research has found.

Data from a large US claims database showed that SGLT2i use was associated with a 31% lower rate of initiation of ULT. “This provides further support for the use of SLGT2i therapy in patients with gout, particularly those with high-risk multimorbidity and polypharmacy,” Greg Challener, MD, a postdoctoral fellow at the Rheumatology and Allergy Clinical Epidemiology Research Center, Massachusetts General Hospital, Boston, said in his presentation of the data at the annual meeting of the American College of Rheumatology.

The first agent of the SGLT2i class, dapagliflozin, was initially approved in the United States a decade ago for treating T2D. Since then, several other “flozins” have become available, and some have also received additional indications for heart failure and albuminuric chronic kidney disease. Several prior studies have linked SGLT2i use with lower rates of gout flares as well as lower likelihood of developing gout in the first place, although not all studies have found this benefit.

Asked about the clinical implications of the new data, Challener said in an interview that “I don’t think we’re quite at the point where this is changing gout management per se, but this just helps us understand that [SGT2is] may have a role at some point, maybe as a combination on top of another agent. Or, in some patients, it really may be enough if they’re already on an SGLT2i where we don’t need to jump to adding allopurinol. Maybe they have tophi, but they were just started on an SGLT2i and they’re not flaring. Typically, you would start those patients on allopurinol, but you could potentially just monitor them if they were just started on one of those [SGLT2i] agents.” 

Asked to comment, session moderator J. Antonio Aviña-Zubieta, MD, PhD, head of the Division of Rheumatology at the University of British Columbia, Vancouver, Canada, and senior scientist at Arthritis Research Canada, said in an interview: “What I can see possibly happening when there’s more evidence is that SGLT2is may be used or even become standard of care as an adjuvant therapy to decrease flares, and by that, decrease the risk of complications.”

 

Reductions in ULT, Flares, and Healthcare Visits

The new study used administrative health data from the multicenter TriNetX Diamond network of electronic medical record and claims data from 92 healthcare sites with 212 million patients. Among those with both T2D and gout who were not taking ULT at baseline, a total of 16,104 initiated SGLT2is and 16,046 initiated glucagon-like peptide 1 receptor agonists (GLP-1 RA).

Propensity score matching was conducted for demographics including age, race, and sex; comorbidities; use of emergency, inpatient, and critical care services; medications; labs; and body mass index. That yielded 11,800 individuals each in the SGLT2i and GLP-1 RA groups.

Over 5 years, 9.9% of the SGLT2i group vs 13.4% of those using GLP-1 RA had initiated ULT, a significant difference with a hazard ratio (HR) of 0.69 (95% CI, 0.64-0.75). The risk for initiation of colchicine for gout flares was 4.7% with SGLT2i vs 6.0% for GLP-1 RA — also a significant difference with an HR of 0.74 (0.65-0.83).

Medical visits for gout occurred in 28.0% vs 28.4% of patients, which also reached statistical significance (HR, 0.94; 95% CI, 0.89-0.99).

Aviña-Zubieta, an author of one of the previous studies finding a reduction in gout flares with SGLT2i, said, “many patients do not want to start gout therapy until they start having more acute attacks. ... So, for a lot of people, it’s a burden taking another pill to prevent one attack. But, if you don’t treat it over time, the attacks come more often. So, can we still delay the initiation of therapy? If you’re not having that many flares, you’re decreasing the burden of the disease and polypharmacy, which I think is the potential benefit in the long run if you already have an indication for the therapy for diabetes. ... These data are supporting that.” 

Indeed, Challener said these data can help in counseling patients. “Taking your SGLT2i for your heart failure and your diabetes is also providing some benefit for your gout, and we know that there is also cardiac benefit when gout is controlled.” 

Challener and Aviña-Zubieta had no disclosures.

A version of this article first appeared on Medscape.com.

WASHINGTON — Use of sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduced the need for urate-lowering therapy (ULT) and gout flare therapies in people who had both type 2 diabetes (T2D) and gout, new research has found.

Data from a large US claims database showed that SGLT2i use was associated with a 31% lower rate of initiation of ULT. “This provides further support for the use of SLGT2i therapy in patients with gout, particularly those with high-risk multimorbidity and polypharmacy,” Greg Challener, MD, a postdoctoral fellow at the Rheumatology and Allergy Clinical Epidemiology Research Center, Massachusetts General Hospital, Boston, said in his presentation of the data at the annual meeting of the American College of Rheumatology.

The first agent of the SGLT2i class, dapagliflozin, was initially approved in the United States a decade ago for treating T2D. Since then, several other “flozins” have become available, and some have also received additional indications for heart failure and albuminuric chronic kidney disease. Several prior studies have linked SGLT2i use with lower rates of gout flares as well as lower likelihood of developing gout in the first place, although not all studies have found this benefit.

Asked about the clinical implications of the new data, Challener said in an interview that “I don’t think we’re quite at the point where this is changing gout management per se, but this just helps us understand that [SGT2is] may have a role at some point, maybe as a combination on top of another agent. Or, in some patients, it really may be enough if they’re already on an SGLT2i where we don’t need to jump to adding allopurinol. Maybe they have tophi, but they were just started on an SGLT2i and they’re not flaring. Typically, you would start those patients on allopurinol, but you could potentially just monitor them if they were just started on one of those [SGLT2i] agents.” 

Asked to comment, session moderator J. Antonio Aviña-Zubieta, MD, PhD, head of the Division of Rheumatology at the University of British Columbia, Vancouver, Canada, and senior scientist at Arthritis Research Canada, said in an interview: “What I can see possibly happening when there’s more evidence is that SGLT2is may be used or even become standard of care as an adjuvant therapy to decrease flares, and by that, decrease the risk of complications.”

 

Reductions in ULT, Flares, and Healthcare Visits

The new study used administrative health data from the multicenter TriNetX Diamond network of electronic medical record and claims data from 92 healthcare sites with 212 million patients. Among those with both T2D and gout who were not taking ULT at baseline, a total of 16,104 initiated SGLT2is and 16,046 initiated glucagon-like peptide 1 receptor agonists (GLP-1 RA).

Propensity score matching was conducted for demographics including age, race, and sex; comorbidities; use of emergency, inpatient, and critical care services; medications; labs; and body mass index. That yielded 11,800 individuals each in the SGLT2i and GLP-1 RA groups.

Over 5 years, 9.9% of the SGLT2i group vs 13.4% of those using GLP-1 RA had initiated ULT, a significant difference with a hazard ratio (HR) of 0.69 (95% CI, 0.64-0.75). The risk for initiation of colchicine for gout flares was 4.7% with SGLT2i vs 6.0% for GLP-1 RA — also a significant difference with an HR of 0.74 (0.65-0.83).

Medical visits for gout occurred in 28.0% vs 28.4% of patients, which also reached statistical significance (HR, 0.94; 95% CI, 0.89-0.99).

Aviña-Zubieta, an author of one of the previous studies finding a reduction in gout flares with SGLT2i, said, “many patients do not want to start gout therapy until they start having more acute attacks. ... So, for a lot of people, it’s a burden taking another pill to prevent one attack. But, if you don’t treat it over time, the attacks come more often. So, can we still delay the initiation of therapy? If you’re not having that many flares, you’re decreasing the burden of the disease and polypharmacy, which I think is the potential benefit in the long run if you already have an indication for the therapy for diabetes. ... These data are supporting that.” 

Indeed, Challener said these data can help in counseling patients. “Taking your SGLT2i for your heart failure and your diabetes is also providing some benefit for your gout, and we know that there is also cardiac benefit when gout is controlled.” 

Challener and Aviña-Zubieta had no disclosures.

A version of this article first appeared on Medscape.com.

WASHINGTON — Use of sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduced the need for urate-lowering therapy (ULT) and gout flare therapies in people who had both type 2 diabetes (T2D) and gout, new research has found.

Data from a large US claims database showed that SGLT2i use was associated with a 31% lower rate of initiation of ULT. “This provides further support for the use of SLGT2i therapy in patients with gout, particularly those with high-risk multimorbidity and polypharmacy,” Greg Challener, MD, a postdoctoral fellow at the Rheumatology and Allergy Clinical Epidemiology Research Center, Massachusetts General Hospital, Boston, said in his presentation of the data at the annual meeting of the American College of Rheumatology.

The first agent of the SGLT2i class, dapagliflozin, was initially approved in the United States a decade ago for treating T2D. Since then, several other “flozins” have become available, and some have also received additional indications for heart failure and albuminuric chronic kidney disease. Several prior studies have linked SGLT2i use with lower rates of gout flares as well as lower likelihood of developing gout in the first place, although not all studies have found this benefit.

Asked about the clinical implications of the new data, Challener said in an interview that “I don’t think we’re quite at the point where this is changing gout management per se, but this just helps us understand that [SGT2is] may have a role at some point, maybe as a combination on top of another agent. Or, in some patients, it really may be enough if they’re already on an SGLT2i where we don’t need to jump to adding allopurinol. Maybe they have tophi, but they were just started on an SGLT2i and they’re not flaring. Typically, you would start those patients on allopurinol, but you could potentially just monitor them if they were just started on one of those [SGLT2i] agents.” 

Asked to comment, session moderator J. Antonio Aviña-Zubieta, MD, PhD, head of the Division of Rheumatology at the University of British Columbia, Vancouver, Canada, and senior scientist at Arthritis Research Canada, said in an interview: “What I can see possibly happening when there’s more evidence is that SGLT2is may be used or even become standard of care as an adjuvant therapy to decrease flares, and by that, decrease the risk of complications.”

 

Reductions in ULT, Flares, and Healthcare Visits

The new study used administrative health data from the multicenter TriNetX Diamond network of electronic medical record and claims data from 92 healthcare sites with 212 million patients. Among those with both T2D and gout who were not taking ULT at baseline, a total of 16,104 initiated SGLT2is and 16,046 initiated glucagon-like peptide 1 receptor agonists (GLP-1 RA).

Propensity score matching was conducted for demographics including age, race, and sex; comorbidities; use of emergency, inpatient, and critical care services; medications; labs; and body mass index. That yielded 11,800 individuals each in the SGLT2i and GLP-1 RA groups.

Over 5 years, 9.9% of the SGLT2i group vs 13.4% of those using GLP-1 RA had initiated ULT, a significant difference with a hazard ratio (HR) of 0.69 (95% CI, 0.64-0.75). The risk for initiation of colchicine for gout flares was 4.7% with SGLT2i vs 6.0% for GLP-1 RA — also a significant difference with an HR of 0.74 (0.65-0.83).

Medical visits for gout occurred in 28.0% vs 28.4% of patients, which also reached statistical significance (HR, 0.94; 95% CI, 0.89-0.99).

Aviña-Zubieta, an author of one of the previous studies finding a reduction in gout flares with SGLT2i, said, “many patients do not want to start gout therapy until they start having more acute attacks. ... So, for a lot of people, it’s a burden taking another pill to prevent one attack. But, if you don’t treat it over time, the attacks come more often. So, can we still delay the initiation of therapy? If you’re not having that many flares, you’re decreasing the burden of the disease and polypharmacy, which I think is the potential benefit in the long run if you already have an indication for the therapy for diabetes. ... These data are supporting that.” 

Indeed, Challener said these data can help in counseling patients. “Taking your SGLT2i for your heart failure and your diabetes is also providing some benefit for your gout, and we know that there is also cardiac benefit when gout is controlled.” 

Challener and Aviña-Zubieta had no disclosures.

A version of this article first appeared on Medscape.com.

WASHINGTON — New draft guidance on the use of musculoskeletal ultrasound (MSUS) for diagnosis, monitoring, and prognosis of psoriatic arthritis was presented at the American College of Rheumatology (ACR) 2024 Annual Meeting. The new recommendations, intended to update 2012 guidance on rheumatologic use of MSUS, will go through another round of expert committee voting before being finalized and published.

“Even in the last 12 years, we’ve seen substantive advances, and there’s been significant improvements in musculoskeletal ultrasound technology,” Veena K. Ranganath, MD, professor of clinical medicine at the University of California, Los Angeles, and director of their Rheumatology Fellowship Musculoskeletal Ultrasound Training Program, told attendees. She noted that more than 30,000 articles on MSUS and arthritis have been published since the 2012 guidance. “We’ve seen mastery in teaching and really a wide distribution of this education to the next generation of dermatologists, and this has led to significant increases in the use of musculoskeletal ultrasound in clinical practices.” 

She also noted there have been significant improvements in therapeutic agents and strategies in psoriatic arthritis medications and that differences in today’s patients compared with those of a decade ago have influenced clinical questions related to the use of MSUS in rheumatology. 

To develop the guidelines, a committee identified key domains and relevant clinical questions for ultrasonography using the PICO model (patient/population, intervention, comparison, and outcomes). A review of the literature published since 1993 in PubMed, Embase, and the Cochrane Database provided the evidence base, and a committee of 11 experts voted on the strength of the evidence for 22 statements. They rejected two that lacked consensus, and another round of voting will occur before the guidance is published. 

Michael Stein, MD, assistant professor of medicine in rheumatology at McGill University in Montreal, Quebec, Canada, who was not involved in the guidance development, said he hopes and expects this new guidance will help persuade more clinicians to recognize the value of using MSUS in their practice. 

“Number one, it’ll highlight the huge amount of data that exist that support using this technology for managing these groups of patients, among others, and I think it’ll also highlight the enormous number of questions that still exist that will hopefully be answered in the future, promoting new research,” Stein told this news organization. 

“I do think it does allow people who are not comfortable with technology to adopt technology in a very gradual way and make it less threatening,” Stein added. 

“Ultrasound is becoming part of the landscape, and so increasingly, we’re trying to promote it as being part of the standard of care, or at least an adjunct to care. I commend the committee for doing all this amazing work.” 

 

Predicting and Diagnosing Early Psoriatic Arthritis

Catherine J. Bakewell, MD, a rheumatologist at Intermountain Health in Salt Lake City, Utah, reviewed the committee’s statements, starting with strong consensus that MSUS can help with diagnosing early psoriatic arthritis. Evidence has shown that patients with psoriasis who have subclinical synovitis, enthesitis, and other features have gone on to develop psoriatic arthritis, and researchers have documented the transition with ultrasonography. 

“We can use it to enhance our CASPAR classification criteria” by using ultrasound to change how clinicians apply the classification criteria, Bakewell said. “For example, in order to go through those classification criteria, a patient has to have confirmed inflammatory articular disease, either the joint synthesis or spine, and ultrasound can help clarify that state for us.” 

She also noted the potential for ultrasonography to help as a screening tool because studies have suggested that dermatologists’ use of handheld ultrasound transducers can help in screening appropriate patients to refer to rheumatologists. 

Patients with psoriasis being evaluated for a potential early psoriatic arthritis diagnosis should undergo MSUS of the bilateral quadriceps tendon, patellar ligament, Achilles tendon, and plantar fascia entheses at a minimum, per moderate consensus. 

“This truly is just designed to be the highest bang for your buck. This is designed for clinicians in practice,” Bakewell said. She noted criticism about the exclusion of upper extremities — something that will be discussed in the future published paper — but one reason that was excluded is because common findings have occurred in healthy individuals in some areas. 

Moderate consensus also supported reliance on entheseal features — including hypoechogenicity, thickening, Doppler signal, bone erosions, enthesophytes/calcifications, and bursal enlargement — to support a diagnosis. Interpretation of entheseal changes in patients with psoriasis should take into account characteristics such as age, body mass index (BMI), and biomechanical stress.

“There are numerous articles already existing pointing out that people who are over the age of 50 with a BMI over 30 kg/m2 or who have higher levels of biomechanical stress will score more highly on endocytoscoring systems, even in the absence of an underlying disorder,” Bakewell said. Among the mitigating strategies proposed in the literature are to have at least three positive sites to qualify for an indication or to look at the specificity of each elementary lesion. “Whatever mitigating strategy the clinician chooses to use, they need to bear in mind some of these features are not exclusive to spondyloarthritis,” she said. “It has to be taken in the clinical context.” 

Scanning the hand, wrist, foot, and relevant symptomatic joints with MSUS to diagnose early psoriatic arthritis in patients with psoriasis received strong consensus. Intracapsular findings of synovitis and erosions may help support an early diagnosis in patients with psoriasis. “These are not obviously specific to psoriatic arthritis but support the diagnosis” with moderate consensus, Bakewell said. “The more specific findings are these extracapsular findings — which did attain a strong level of consensus — which are enthesitis, tenosynovitis, and dactylitis, all supporting that diagnosis of early psoriatic arthritis.” 

For patients with psoriatic arthritis, the cutoff for defining a positive joint received moderate consensus for grayscale (GS) of at least 2 or at least 1 with power Doppler (PD) of at least 1. 

Strong consensus supported confirming the presence of dactylitis in patients with psoriasis or psoriatic arthritis through a combination of features including tenosynovitis, subcutaneous edema, soft tissue thickening, synovitis, paratenonitis, and pulley thickening. 

“I will also note that enthesitis is missing from this definition of dactylitis,” Bakewell said. “It is, however, a feature that is detectable with those higher-frequency transducers, but this is a relatively early area of research and did not make it into this guidance statement.” 

Moderate consensus supported determination of an increased risk of radiographic erosions in patients with a dactylitis PD score of at least 1. 

“We know as far back as 2005, Brockbank et al taught us that the dactylitic digit is associated with radiographic erosion in that particular digit,” Bakewell said. “Flash forward all the way to 2021: Dubash et al published the paper, ‘Dactylitis is an indicator of a more severe phenotype independently associated with greater swollen joint counts, C-reactive protein, ultrasound synovitis, and erosive damage,’ showing us that this is more than just that particular digit. It is a more severe phenotype, and very minimal Doppler signal, just 1+, is associated with erosive damage.”

 

Progression of Psoriatic Arthritis and Shared Decision-Making

Strong consensus existed for all statements related to progression of psoriatic arthritis and the role of MSUS in shared decision-making. The first is that synovitis and enthesitis in MSUS can predict radiographic progression and worsening of patient-related outcomes. Second, sonographic features — including increased Doppler signal in synovitis, enthesitis, and tenosynovitis — and presence of bone erosions and dactylitis can help inform decisions regarding therapy escalation.

“This is the first treatment management–specific statement we have made, but we feel this to be justified because each of these ultrasonographic features is associated with overall inflammatory burden and worse outcomes, be it health assessment questionnaires, disability index, or patient-reported outcomes to harder endpoints, such as radiographic erosions or relapse of clinical remission,” Bakewell said. 

Finally, MSUS can help inform patients of their disease activity to assist in shared decision-making regarding escalation or de-escalation of therapy.

“We’ve all had this in our practices. You’ve had the patient in front of you who is very inflamed, and they say, ‘Doctor, can’t I please use doTERRA oils? Do I really need to go on one of these toxic drugs? I’ve read the package insert,’” Bakewell said. “Aside from having that conversation about the relative risk–benefit of any individual medication that you recommend, it’s helpful to put the ultrasound transducer on the patient, show them the fire of the Doppler, show them the erosion, show them the damage that is being done. It comes to life for them, especially if they’re not suffering that much with pain or stiffness.” 

Bakewell also addressed patients at the other end of the pain spectrum who are suffering more. “You’ve also probably had the patient with psoriatic arthritis and fibromyalgia who comes in and tells you, ‘Doctor, my psoriatic arthritis has been terrible. I’m flaring. I need more immune-suppressing medication,’” she said. “Their exam looks pretty good, and it’s helpful to put that transducer on them and show them the absence of Doppler signal, show them that you’re taking them very seriously. You didn’t just squeeze them and say they’re fine, but you looked more deeply. You looked underneath the skin, and that helps with that patient–provider understanding and communication. I use this every day.” 

 

Clarifying Disease State and Defining Remission

As with patients with psoriasis undergoing evaluation, there was strong consensus for interpreting entheseal changes in psoriatic arthritis in the context of patient characteristics such as age, BMI, and biomechanical stress.

There was moderate consensus for confirming psoriatic arthritis flare with MSUS. Bakewell noted that many have seen in their practices how physical exams can be misleading, such as when a patient appears clinically normal but has ongoing synovitis, or on the flip side, the patient has a swollen joint but nothing is lighting up with Doppler on the ultrasound.

All of the statements on MSUS for remission received moderate consensus. These included defining MSUS remission as a PD score of 0 in entheses and synovial tissues and defining ultrasonographic remission as a total PD ultrasound score of 0, summing all analyzed joints and entheses, at a single given time point.

When using MSUS to evaluate for remission, it’s reasonable to screen the lower-extremity entheses, wrists, metacarpophalangeal joints, interphalangeal hand joints, metatarsophalangeal joints, and relevant symptomatic joints. The inflammatory features to evaluate to confirm ultrasound-defined remission include PD enthesitis, GS and PD synovitis, tenosynovitis, and dactylitis. Finally, for those in remission, subclinical inflammation detected by MSUS likely predicts a higher rate of flare. 

During the discussion, Bakewell reiterated that MSUS should be regarded as a tool for patient subsets who can benefit from its use, rather than being used routinely across large patient groups without a clear purpose. “It’s used to answer a question,” she said. “If you’re going to demonstrate the efficacy of a tool, you have to use it appropriately, aka when there’s a question. We don’t need to ultrasound every patient every visit.”

No external funding for the development of the guidance was noted. Ranganath has reported receiving research support from Bristol Myers Squibb and Mallinckrodt. Bakewell has reported receiving speaking/consulting fees from AbbVie, UCB, Lilly, Janssen, Novartis, Sanofi/Regeneron/Genzyme, and Pfizer. Stein had no disclosures. 

 

A version of this article first appeared on Medscape.com.

WASHINGTON — New draft guidance on the use of musculoskeletal ultrasound (MSUS) for diagnosis, monitoring, and prognosis of psoriatic arthritis was presented at the American College of Rheumatology (ACR) 2024 Annual Meeting. The new recommendations, intended to update 2012 guidance on rheumatologic use of MSUS, will go through another round of expert committee voting before being finalized and published.

“Even in the last 12 years, we’ve seen substantive advances, and there’s been significant improvements in musculoskeletal ultrasound technology,” Veena K. Ranganath, MD, professor of clinical medicine at the University of California, Los Angeles, and director of their Rheumatology Fellowship Musculoskeletal Ultrasound Training Program, told attendees. She noted that more than 30,000 articles on MSUS and arthritis have been published since the 2012 guidance. “We’ve seen mastery in teaching and really a wide distribution of this education to the next generation of dermatologists, and this has led to significant increases in the use of musculoskeletal ultrasound in clinical practices.” 

She also noted there have been significant improvements in therapeutic agents and strategies in psoriatic arthritis medications and that differences in today’s patients compared with those of a decade ago have influenced clinical questions related to the use of MSUS in rheumatology. 

To develop the guidelines, a committee identified key domains and relevant clinical questions for ultrasonography using the PICO model (patient/population, intervention, comparison, and outcomes). A review of the literature published since 1993 in PubMed, Embase, and the Cochrane Database provided the evidence base, and a committee of 11 experts voted on the strength of the evidence for 22 statements. They rejected two that lacked consensus, and another round of voting will occur before the guidance is published. 

Michael Stein, MD, assistant professor of medicine in rheumatology at McGill University in Montreal, Quebec, Canada, who was not involved in the guidance development, said he hopes and expects this new guidance will help persuade more clinicians to recognize the value of using MSUS in their practice. 

“Number one, it’ll highlight the huge amount of data that exist that support using this technology for managing these groups of patients, among others, and I think it’ll also highlight the enormous number of questions that still exist that will hopefully be answered in the future, promoting new research,” Stein told this news organization. 

“I do think it does allow people who are not comfortable with technology to adopt technology in a very gradual way and make it less threatening,” Stein added. 

“Ultrasound is becoming part of the landscape, and so increasingly, we’re trying to promote it as being part of the standard of care, or at least an adjunct to care. I commend the committee for doing all this amazing work.” 

 

Predicting and Diagnosing Early Psoriatic Arthritis

Catherine J. Bakewell, MD, a rheumatologist at Intermountain Health in Salt Lake City, Utah, reviewed the committee’s statements, starting with strong consensus that MSUS can help with diagnosing early psoriatic arthritis. Evidence has shown that patients with psoriasis who have subclinical synovitis, enthesitis, and other features have gone on to develop psoriatic arthritis, and researchers have documented the transition with ultrasonography. 

“We can use it to enhance our CASPAR classification criteria” by using ultrasound to change how clinicians apply the classification criteria, Bakewell said. “For example, in order to go through those classification criteria, a patient has to have confirmed inflammatory articular disease, either the joint synthesis or spine, and ultrasound can help clarify that state for us.” 

She also noted the potential for ultrasonography to help as a screening tool because studies have suggested that dermatologists’ use of handheld ultrasound transducers can help in screening appropriate patients to refer to rheumatologists. 

Patients with psoriasis being evaluated for a potential early psoriatic arthritis diagnosis should undergo MSUS of the bilateral quadriceps tendon, patellar ligament, Achilles tendon, and plantar fascia entheses at a minimum, per moderate consensus. 

“This truly is just designed to be the highest bang for your buck. This is designed for clinicians in practice,” Bakewell said. She noted criticism about the exclusion of upper extremities — something that will be discussed in the future published paper — but one reason that was excluded is because common findings have occurred in healthy individuals in some areas. 

Moderate consensus also supported reliance on entheseal features — including hypoechogenicity, thickening, Doppler signal, bone erosions, enthesophytes/calcifications, and bursal enlargement — to support a diagnosis. Interpretation of entheseal changes in patients with psoriasis should take into account characteristics such as age, body mass index (BMI), and biomechanical stress.

“There are numerous articles already existing pointing out that people who are over the age of 50 with a BMI over 30 kg/m2 or who have higher levels of biomechanical stress will score more highly on endocytoscoring systems, even in the absence of an underlying disorder,” Bakewell said. Among the mitigating strategies proposed in the literature are to have at least three positive sites to qualify for an indication or to look at the specificity of each elementary lesion. “Whatever mitigating strategy the clinician chooses to use, they need to bear in mind some of these features are not exclusive to spondyloarthritis,” she said. “It has to be taken in the clinical context.” 

Scanning the hand, wrist, foot, and relevant symptomatic joints with MSUS to diagnose early psoriatic arthritis in patients with psoriasis received strong consensus. Intracapsular findings of synovitis and erosions may help support an early diagnosis in patients with psoriasis. “These are not obviously specific to psoriatic arthritis but support the diagnosis” with moderate consensus, Bakewell said. “The more specific findings are these extracapsular findings — which did attain a strong level of consensus — which are enthesitis, tenosynovitis, and dactylitis, all supporting that diagnosis of early psoriatic arthritis.” 

For patients with psoriatic arthritis, the cutoff for defining a positive joint received moderate consensus for grayscale (GS) of at least 2 or at least 1 with power Doppler (PD) of at least 1. 

Strong consensus supported confirming the presence of dactylitis in patients with psoriasis or psoriatic arthritis through a combination of features including tenosynovitis, subcutaneous edema, soft tissue thickening, synovitis, paratenonitis, and pulley thickening. 

“I will also note that enthesitis is missing from this definition of dactylitis,” Bakewell said. “It is, however, a feature that is detectable with those higher-frequency transducers, but this is a relatively early area of research and did not make it into this guidance statement.” 

Moderate consensus supported determination of an increased risk of radiographic erosions in patients with a dactylitis PD score of at least 1. 

“We know as far back as 2005, Brockbank et al taught us that the dactylitic digit is associated with radiographic erosion in that particular digit,” Bakewell said. “Flash forward all the way to 2021: Dubash et al published the paper, ‘Dactylitis is an indicator of a more severe phenotype independently associated with greater swollen joint counts, C-reactive protein, ultrasound synovitis, and erosive damage,’ showing us that this is more than just that particular digit. It is a more severe phenotype, and very minimal Doppler signal, just 1+, is associated with erosive damage.”

 

Progression of Psoriatic Arthritis and Shared Decision-Making

Strong consensus existed for all statements related to progression of psoriatic arthritis and the role of MSUS in shared decision-making. The first is that synovitis and enthesitis in MSUS can predict radiographic progression and worsening of patient-related outcomes. Second, sonographic features — including increased Doppler signal in synovitis, enthesitis, and tenosynovitis — and presence of bone erosions and dactylitis can help inform decisions regarding therapy escalation.

“This is the first treatment management–specific statement we have made, but we feel this to be justified because each of these ultrasonographic features is associated with overall inflammatory burden and worse outcomes, be it health assessment questionnaires, disability index, or patient-reported outcomes to harder endpoints, such as radiographic erosions or relapse of clinical remission,” Bakewell said. 

Finally, MSUS can help inform patients of their disease activity to assist in shared decision-making regarding escalation or de-escalation of therapy.

“We’ve all had this in our practices. You’ve had the patient in front of you who is very inflamed, and they say, ‘Doctor, can’t I please use doTERRA oils? Do I really need to go on one of these toxic drugs? I’ve read the package insert,’” Bakewell said. “Aside from having that conversation about the relative risk–benefit of any individual medication that you recommend, it’s helpful to put the ultrasound transducer on the patient, show them the fire of the Doppler, show them the erosion, show them the damage that is being done. It comes to life for them, especially if they’re not suffering that much with pain or stiffness.” 

Bakewell also addressed patients at the other end of the pain spectrum who are suffering more. “You’ve also probably had the patient with psoriatic arthritis and fibromyalgia who comes in and tells you, ‘Doctor, my psoriatic arthritis has been terrible. I’m flaring. I need more immune-suppressing medication,’” she said. “Their exam looks pretty good, and it’s helpful to put that transducer on them and show them the absence of Doppler signal, show them that you’re taking them very seriously. You didn’t just squeeze them and say they’re fine, but you looked more deeply. You looked underneath the skin, and that helps with that patient–provider understanding and communication. I use this every day.” 

 

Clarifying Disease State and Defining Remission

As with patients with psoriasis undergoing evaluation, there was strong consensus for interpreting entheseal changes in psoriatic arthritis in the context of patient characteristics such as age, BMI, and biomechanical stress.

There was moderate consensus for confirming psoriatic arthritis flare with MSUS. Bakewell noted that many have seen in their practices how physical exams can be misleading, such as when a patient appears clinically normal but has ongoing synovitis, or on the flip side, the patient has a swollen joint but nothing is lighting up with Doppler on the ultrasound.

All of the statements on MSUS for remission received moderate consensus. These included defining MSUS remission as a PD score of 0 in entheses and synovial tissues and defining ultrasonographic remission as a total PD ultrasound score of 0, summing all analyzed joints and entheses, at a single given time point.

When using MSUS to evaluate for remission, it’s reasonable to screen the lower-extremity entheses, wrists, metacarpophalangeal joints, interphalangeal hand joints, metatarsophalangeal joints, and relevant symptomatic joints. The inflammatory features to evaluate to confirm ultrasound-defined remission include PD enthesitis, GS and PD synovitis, tenosynovitis, and dactylitis. Finally, for those in remission, subclinical inflammation detected by MSUS likely predicts a higher rate of flare. 

During the discussion, Bakewell reiterated that MSUS should be regarded as a tool for patient subsets who can benefit from its use, rather than being used routinely across large patient groups without a clear purpose. “It’s used to answer a question,” she said. “If you’re going to demonstrate the efficacy of a tool, you have to use it appropriately, aka when there’s a question. We don’t need to ultrasound every patient every visit.”

No external funding for the development of the guidance was noted. Ranganath has reported receiving research support from Bristol Myers Squibb and Mallinckrodt. Bakewell has reported receiving speaking/consulting fees from AbbVie, UCB, Lilly, Janssen, Novartis, Sanofi/Regeneron/Genzyme, and Pfizer. Stein had no disclosures. 

 

A version of this article first appeared on Medscape.com.

WASHINGTON — New draft guidance on the use of musculoskeletal ultrasound (MSUS) for diagnosis, monitoring, and prognosis of psoriatic arthritis was presented at the American College of Rheumatology (ACR) 2024 Annual Meeting. The new recommendations, intended to update 2012 guidance on rheumatologic use of MSUS, will go through another round of expert committee voting before being finalized and published.

“Even in the last 12 years, we’ve seen substantive advances, and there’s been significant improvements in musculoskeletal ultrasound technology,” Veena K. Ranganath, MD, professor of clinical medicine at the University of California, Los Angeles, and director of their Rheumatology Fellowship Musculoskeletal Ultrasound Training Program, told attendees. She noted that more than 30,000 articles on MSUS and arthritis have been published since the 2012 guidance. “We’ve seen mastery in teaching and really a wide distribution of this education to the next generation of dermatologists, and this has led to significant increases in the use of musculoskeletal ultrasound in clinical practices.” 

She also noted there have been significant improvements in therapeutic agents and strategies in psoriatic arthritis medications and that differences in today’s patients compared with those of a decade ago have influenced clinical questions related to the use of MSUS in rheumatology. 

To develop the guidelines, a committee identified key domains and relevant clinical questions for ultrasonography using the PICO model (patient/population, intervention, comparison, and outcomes). A review of the literature published since 1993 in PubMed, Embase, and the Cochrane Database provided the evidence base, and a committee of 11 experts voted on the strength of the evidence for 22 statements. They rejected two that lacked consensus, and another round of voting will occur before the guidance is published. 

Michael Stein, MD, assistant professor of medicine in rheumatology at McGill University in Montreal, Quebec, Canada, who was not involved in the guidance development, said he hopes and expects this new guidance will help persuade more clinicians to recognize the value of using MSUS in their practice. 

“Number one, it’ll highlight the huge amount of data that exist that support using this technology for managing these groups of patients, among others, and I think it’ll also highlight the enormous number of questions that still exist that will hopefully be answered in the future, promoting new research,” Stein told this news organization. 

“I do think it does allow people who are not comfortable with technology to adopt technology in a very gradual way and make it less threatening,” Stein added. 

“Ultrasound is becoming part of the landscape, and so increasingly, we’re trying to promote it as being part of the standard of care, or at least an adjunct to care. I commend the committee for doing all this amazing work.” 

 

Predicting and Diagnosing Early Psoriatic Arthritis

Catherine J. Bakewell, MD, a rheumatologist at Intermountain Health in Salt Lake City, Utah, reviewed the committee’s statements, starting with strong consensus that MSUS can help with diagnosing early psoriatic arthritis. Evidence has shown that patients with psoriasis who have subclinical synovitis, enthesitis, and other features have gone on to develop psoriatic arthritis, and researchers have documented the transition with ultrasonography. 

“We can use it to enhance our CASPAR classification criteria” by using ultrasound to change how clinicians apply the classification criteria, Bakewell said. “For example, in order to go through those classification criteria, a patient has to have confirmed inflammatory articular disease, either the joint synthesis or spine, and ultrasound can help clarify that state for us.” 

She also noted the potential for ultrasonography to help as a screening tool because studies have suggested that dermatologists’ use of handheld ultrasound transducers can help in screening appropriate patients to refer to rheumatologists. 

Patients with psoriasis being evaluated for a potential early psoriatic arthritis diagnosis should undergo MSUS of the bilateral quadriceps tendon, patellar ligament, Achilles tendon, and plantar fascia entheses at a minimum, per moderate consensus. 

“This truly is just designed to be the highest bang for your buck. This is designed for clinicians in practice,” Bakewell said. She noted criticism about the exclusion of upper extremities — something that will be discussed in the future published paper — but one reason that was excluded is because common findings have occurred in healthy individuals in some areas. 

Moderate consensus also supported reliance on entheseal features — including hypoechogenicity, thickening, Doppler signal, bone erosions, enthesophytes/calcifications, and bursal enlargement — to support a diagnosis. Interpretation of entheseal changes in patients with psoriasis should take into account characteristics such as age, body mass index (BMI), and biomechanical stress.

“There are numerous articles already existing pointing out that people who are over the age of 50 with a BMI over 30 kg/m2 or who have higher levels of biomechanical stress will score more highly on endocytoscoring systems, even in the absence of an underlying disorder,” Bakewell said. Among the mitigating strategies proposed in the literature are to have at least three positive sites to qualify for an indication or to look at the specificity of each elementary lesion. “Whatever mitigating strategy the clinician chooses to use, they need to bear in mind some of these features are not exclusive to spondyloarthritis,” she said. “It has to be taken in the clinical context.” 

Scanning the hand, wrist, foot, and relevant symptomatic joints with MSUS to diagnose early psoriatic arthritis in patients with psoriasis received strong consensus. Intracapsular findings of synovitis and erosions may help support an early diagnosis in patients with psoriasis. “These are not obviously specific to psoriatic arthritis but support the diagnosis” with moderate consensus, Bakewell said. “The more specific findings are these extracapsular findings — which did attain a strong level of consensus — which are enthesitis, tenosynovitis, and dactylitis, all supporting that diagnosis of early psoriatic arthritis.” 

For patients with psoriatic arthritis, the cutoff for defining a positive joint received moderate consensus for grayscale (GS) of at least 2 or at least 1 with power Doppler (PD) of at least 1. 

Strong consensus supported confirming the presence of dactylitis in patients with psoriasis or psoriatic arthritis through a combination of features including tenosynovitis, subcutaneous edema, soft tissue thickening, synovitis, paratenonitis, and pulley thickening. 

“I will also note that enthesitis is missing from this definition of dactylitis,” Bakewell said. “It is, however, a feature that is detectable with those higher-frequency transducers, but this is a relatively early area of research and did not make it into this guidance statement.” 

Moderate consensus supported determination of an increased risk of radiographic erosions in patients with a dactylitis PD score of at least 1. 

“We know as far back as 2005, Brockbank et al taught us that the dactylitic digit is associated with radiographic erosion in that particular digit,” Bakewell said. “Flash forward all the way to 2021: Dubash et al published the paper, ‘Dactylitis is an indicator of a more severe phenotype independently associated with greater swollen joint counts, C-reactive protein, ultrasound synovitis, and erosive damage,’ showing us that this is more than just that particular digit. It is a more severe phenotype, and very minimal Doppler signal, just 1+, is associated with erosive damage.”

 

Progression of Psoriatic Arthritis and Shared Decision-Making

Strong consensus existed for all statements related to progression of psoriatic arthritis and the role of MSUS in shared decision-making. The first is that synovitis and enthesitis in MSUS can predict radiographic progression and worsening of patient-related outcomes. Second, sonographic features — including increased Doppler signal in synovitis, enthesitis, and tenosynovitis — and presence of bone erosions and dactylitis can help inform decisions regarding therapy escalation.

“This is the first treatment management–specific statement we have made, but we feel this to be justified because each of these ultrasonographic features is associated with overall inflammatory burden and worse outcomes, be it health assessment questionnaires, disability index, or patient-reported outcomes to harder endpoints, such as radiographic erosions or relapse of clinical remission,” Bakewell said. 

Finally, MSUS can help inform patients of their disease activity to assist in shared decision-making regarding escalation or de-escalation of therapy.

“We’ve all had this in our practices. You’ve had the patient in front of you who is very inflamed, and they say, ‘Doctor, can’t I please use doTERRA oils? Do I really need to go on one of these toxic drugs? I’ve read the package insert,’” Bakewell said. “Aside from having that conversation about the relative risk–benefit of any individual medication that you recommend, it’s helpful to put the ultrasound transducer on the patient, show them the fire of the Doppler, show them the erosion, show them the damage that is being done. It comes to life for them, especially if they’re not suffering that much with pain or stiffness.” 

Bakewell also addressed patients at the other end of the pain spectrum who are suffering more. “You’ve also probably had the patient with psoriatic arthritis and fibromyalgia who comes in and tells you, ‘Doctor, my psoriatic arthritis has been terrible. I’m flaring. I need more immune-suppressing medication,’” she said. “Their exam looks pretty good, and it’s helpful to put that transducer on them and show them the absence of Doppler signal, show them that you’re taking them very seriously. You didn’t just squeeze them and say they’re fine, but you looked more deeply. You looked underneath the skin, and that helps with that patient–provider understanding and communication. I use this every day.” 

 

Clarifying Disease State and Defining Remission

As with patients with psoriasis undergoing evaluation, there was strong consensus for interpreting entheseal changes in psoriatic arthritis in the context of patient characteristics such as age, BMI, and biomechanical stress.

There was moderate consensus for confirming psoriatic arthritis flare with MSUS. Bakewell noted that many have seen in their practices how physical exams can be misleading, such as when a patient appears clinically normal but has ongoing synovitis, or on the flip side, the patient has a swollen joint but nothing is lighting up with Doppler on the ultrasound.

All of the statements on MSUS for remission received moderate consensus. These included defining MSUS remission as a PD score of 0 in entheses and synovial tissues and defining ultrasonographic remission as a total PD ultrasound score of 0, summing all analyzed joints and entheses, at a single given time point.

When using MSUS to evaluate for remission, it’s reasonable to screen the lower-extremity entheses, wrists, metacarpophalangeal joints, interphalangeal hand joints, metatarsophalangeal joints, and relevant symptomatic joints. The inflammatory features to evaluate to confirm ultrasound-defined remission include PD enthesitis, GS and PD synovitis, tenosynovitis, and dactylitis. Finally, for those in remission, subclinical inflammation detected by MSUS likely predicts a higher rate of flare. 

During the discussion, Bakewell reiterated that MSUS should be regarded as a tool for patient subsets who can benefit from its use, rather than being used routinely across large patient groups without a clear purpose. “It’s used to answer a question,” she said. “If you’re going to demonstrate the efficacy of a tool, you have to use it appropriately, aka when there’s a question. We don’t need to ultrasound every patient every visit.”

No external funding for the development of the guidance was noted. Ranganath has reported receiving research support from Bristol Myers Squibb and Mallinckrodt. Bakewell has reported receiving speaking/consulting fees from AbbVie, UCB, Lilly, Janssen, Novartis, Sanofi/Regeneron/Genzyme, and Pfizer. Stein had no disclosures. 

 

A version of this article first appeared on Medscape.com.

WASHINGTON — After more than a decade, the American College of Rheumatology has developed new draft guidance for the use of musculoskeletal ultrasound (MSUS) to help with diagnosis, monitoring, and prognosis of rheumatoid arthritis (RA). Though not yet finalized, the statements that came out of a first round of committee voting were unveiled at the annual meeting of the American College of Rheumatology (ACR).

The committee was charged with updating the 2012 recommendations on using MSUS in rheumatology clinical practice, explained Veena K. Ranganath, MD, professor of clinical medicine at the University of California, Los Angeles, and director of their Rheumatology Fellowship Musculoskeletal Ultrasound Training Program. 

More than 30,000 articles on MSUS and any arthritis have been published since 2012, and there have been significant advances and improvements in technology as well as more widespread education and use in rheumatologic clinical practice, Ranganath said. 

“There’s also been advancements in therapeutic agents and therapeutic strategies in use of these medications in rheumatoid arthritis,” Ranganath said. “We all know that the patient of today is very different than the patient of 10 years ago or 20 years ago, so this really impacts the clinical questions we ask of how we need to incorporate musculoskeletal ultrasound into our rheumatology clinical practice.” 

The process of developing the guidance involved determining key domains and then relevant clinical questions for ultrasonography using the PICO model (patient/population, intervention, comparison, and outcomes). Evidence came from a review of relevant literature published since 1993 in PubMed, Embase, and the Cochrane Database. A panel of 11 experts voted on the quality of the evidence as being moderate or strong for 33 statements, rejecting three that had no consensus. The committee will hold another round of voting before the guidance is published.

Erin Arnold, MD, a rheumatologist at Arnold Arthritis & Rheumatology in Skokie, Illinois, said in an interview she believes the new guidance will be “tremendously helpful,” particularly in getting “everybody on the same page” with similar practices and helping enhance diagnosis and response to therapy. 

Having used MSUS for over 20 years, Arnold said watching it evolve and seeing “this type of manuscript being put together as a resource for physicians who are taking care of inflammatory arthritis is exciting.”

“There’s not a single way we really can assess disease activity in our patients, and so having a composite of things that you’re looking at really enhances our ability to understand people’s pain,” Arnold said. 

“When you have a patient in front of you that is in so much pain but doesn’t have any active inflammation, it’s hard to want to further put them at risk with more medication,” she said. “It’s so meaningful to be able to have a conversation about ... what are other complementary interventions? How are they sleeping? How are they eating? What are they taking as far as supplements? What are they doing to decrease that kind of fear and fight-or-flight response that often can drive some of our pain?” 

 

Use of MSUS for Diagnosis Confirmation and Treatment Decisions

Gurjit S. Kaeley, MBBS, professor of medicine, division chief of rheumatology and clinical immunology, and medical director of the Musculoskeletal Ultrasound Program at the University of Florida College of Medicine, Jacksonville, reviewed the final statements for MSUS use with RA.

He said there was strong consensus that adding MSUS to clinical examination can aid diagnosis of early RA in patients with suspected RA, particularly with detection of synovitis, tenosynovitis, and erosions. There was moderate consensus that MSUS detection of tenosynovitis could predict later development of RA. 

“Furthermore, erosions do have a predictive prognostic value in telling us that these patients need more attention and more urgent attention to getting urgent care with disease-modifying medications,” Kaeley said. “Ultrasound scanning for bone erosions on a few target joints was found to be feasible in literature and provides information not available with clinical examination. Furthermore, ultrasound is more sensitive than plain radiography for the detection of erosions.” 

Moderate consensus supported a cutoff of at least 2 mm for erosions when using MSUS for diagnostic purposes. 

Strong consensus supported using MSUS of the wrist, second and third metacarpophalangeal (MCP) joints, and second and third interphalangeal (PIP) joints to aid early RA diagnosis, with moderate consensus that cutoffs of least 2 grayscale (GS) or at least 1 GS with at least 1 power Doppler (PD) at the joint level supports both an RA diagnosis and, in patients already diagnosed with RA, a positive joint.

“Grayscale-only definitions were included since equipment may not have sensitive Doppler,” Kaeley said.

Strong consensus supported scanning only a reduced set of representative or symptomatic joints to monitor disease activity with MSUS. 

 

Inflammatory Signs, Disease Progression, and Flares

There was also strong consensus for using MSUS in patients with established RA and comorbidities to help distinguish between RA-related inflammation versus inflammation from other conditions, such as gout or calcium pyrophosphate deposition disease, or versus non–RA-related pain, such as that from fibromyalgia. 

Patients with fibromyalgia, for example, “tend to have more steroid exposure and a high prevalence of biologic use because the composite disease scores tend to overestimate disease activity, especially when compared to ultrasound assessment,” Kaeley said.

Moderate consensus supported using MSUS in patients with established RA to objectively evaluate inflammation so as to eliminate age-related bias.

While MSUS signs of synovitis had only moderate consensus to be associated with radiographic progression and decline in patient-reported outcomes for patients with early RA, consensus was strong for this association in patients with established RA.

In terms of predicting disease progression with MSUS monitoring of RA disease activity, moderate consensus supported scanning the wrists and MCPs and PIPs of the hands and using the dorsal view. Kaeley emphasized that ultrasound is a clinical tool that should be used to answer a clinical question, so the sonographer or clinician needs to provide guidance on the areas to be scanned. 

Multiple standardized scoring systems exist for predicting RA disease progression, but there is no consensus on which is the most effective, and there is only moderate consensus about the validity of using dichotomous scoring with an established cutoff for a positive joint.

The combination of MSUS with clinical examination appears to be more effective at confirming RA flares than using only clinical examination, and in certain patients with established RA, MSUS may provide insights into subclinical disease activity to help maintain remission and/or potentially guide treatment decisions, “especially when coming across de-escalation therapy decisions,” Kaeley said.

Despite the negative results of treat-to-target trials that tested MSUS as a routine tool in all patients, the committee achieved strong consensus on the potential value of using MSUS in early RA to clarify clinical status and/or help achieve low disease activity or remission in certain patient populations, “such as those with patient/provider discordance or difficult physical examinations,” Kaeley said. 

 

Therapy Response, Remission, and Shared Decision-Making

Moderate consensus supported acknowledgment that using MSUS to assess response to therapy could be affected by obesity and that MSUS can distinguish active synovitis symptoms from other pain sources in difficult-to-treat RA.

In patients with established RA, the feasibility of scanning the wrists, MCPs, PIPs, and relevant symptomatic joints for remission evaluation received moderate consensus. Meanwhile, strong consensus supported the idea that increasing the number of joints scanned with MSUS could increase the certainty of the patient having achieved remission, though the guidance acknowledges that “this must be balanced against the feasibility within the context of clinical care.” 

For confirming RA remission via MSUS, strong consensus supported using GS and PD synovitis and tenosynovitis findings. But consensus was moderate for using the combination of no PD signal and minimal synovial hypertrophy to define ultrasonographic remission and for the use of MSUS detection of subclinical inflammation to predict higher flare rates for those in clinical remission.

The committee moderately agreed that MSUS can enhance patient engagement and understanding of their disease to support personalized treatment decisions, such as adjusting disease-modifying antirheumatic drug regimens.

Finally, the committee broadly agreed that “the integration of musculoskeletal ultrasound presents significant advantages in shared decision-making between healthcare providers and patients,” Kaeley said. “Ultrasound, especially with Doppler technique, provides critical insights into disease activity and structural changes not always apparent during standard examination.” 

Arnold said she particularly appreciated that the committee, rather than prescribing a specific exam, opted to be more generalizable so that people use the guidance in the context that makes the most sense for them clinically. She said it’s an incredible tool, without excluding the importance of a patient’s labs and physical examination. 

“It’s helped us make diagnoses in patients who were difficult to diagnose. It’s helped us to understand response to therapy or no response to therapy,” she said. “It makes me question all the studies that I see done on medications where they’re not looking at some type of advanced imaging.” 

No external funding was noted for the development of the guidance. Ranganath has reported receiving research support from Bristol-Myers Squibb and Mallinckrodt. Kaeley has reported receiving research funding from AbbVie, Bristol-Myers Squibb, Gilead/Galapagos, Janssen, and Novartis. Arnold had no disclosures.

A version of this article first appeared on Medscape.com.

WASHINGTON — After more than a decade, the American College of Rheumatology has developed new draft guidance for the use of musculoskeletal ultrasound (MSUS) to help with diagnosis, monitoring, and prognosis of rheumatoid arthritis (RA). Though not yet finalized, the statements that came out of a first round of committee voting were unveiled at the annual meeting of the American College of Rheumatology (ACR).

The committee was charged with updating the 2012 recommendations on using MSUS in rheumatology clinical practice, explained Veena K. Ranganath, MD, professor of clinical medicine at the University of California, Los Angeles, and director of their Rheumatology Fellowship Musculoskeletal Ultrasound Training Program. 

More than 30,000 articles on MSUS and any arthritis have been published since 2012, and there have been significant advances and improvements in technology as well as more widespread education and use in rheumatologic clinical practice, Ranganath said. 

“There’s also been advancements in therapeutic agents and therapeutic strategies in use of these medications in rheumatoid arthritis,” Ranganath said. “We all know that the patient of today is very different than the patient of 10 years ago or 20 years ago, so this really impacts the clinical questions we ask of how we need to incorporate musculoskeletal ultrasound into our rheumatology clinical practice.” 

The process of developing the guidance involved determining key domains and then relevant clinical questions for ultrasonography using the PICO model (patient/population, intervention, comparison, and outcomes). Evidence came from a review of relevant literature published since 1993 in PubMed, Embase, and the Cochrane Database. A panel of 11 experts voted on the quality of the evidence as being moderate or strong for 33 statements, rejecting three that had no consensus. The committee will hold another round of voting before the guidance is published.

Erin Arnold, MD, a rheumatologist at Arnold Arthritis & Rheumatology in Skokie, Illinois, said in an interview she believes the new guidance will be “tremendously helpful,” particularly in getting “everybody on the same page” with similar practices and helping enhance diagnosis and response to therapy. 

Having used MSUS for over 20 years, Arnold said watching it evolve and seeing “this type of manuscript being put together as a resource for physicians who are taking care of inflammatory arthritis is exciting.”

“There’s not a single way we really can assess disease activity in our patients, and so having a composite of things that you’re looking at really enhances our ability to understand people’s pain,” Arnold said. 

“When you have a patient in front of you that is in so much pain but doesn’t have any active inflammation, it’s hard to want to further put them at risk with more medication,” she said. “It’s so meaningful to be able to have a conversation about ... what are other complementary interventions? How are they sleeping? How are they eating? What are they taking as far as supplements? What are they doing to decrease that kind of fear and fight-or-flight response that often can drive some of our pain?” 

 

Use of MSUS for Diagnosis Confirmation and Treatment Decisions

Gurjit S. Kaeley, MBBS, professor of medicine, division chief of rheumatology and clinical immunology, and medical director of the Musculoskeletal Ultrasound Program at the University of Florida College of Medicine, Jacksonville, reviewed the final statements for MSUS use with RA.

He said there was strong consensus that adding MSUS to clinical examination can aid diagnosis of early RA in patients with suspected RA, particularly with detection of synovitis, tenosynovitis, and erosions. There was moderate consensus that MSUS detection of tenosynovitis could predict later development of RA. 

“Furthermore, erosions do have a predictive prognostic value in telling us that these patients need more attention and more urgent attention to getting urgent care with disease-modifying medications,” Kaeley said. “Ultrasound scanning for bone erosions on a few target joints was found to be feasible in literature and provides information not available with clinical examination. Furthermore, ultrasound is more sensitive than plain radiography for the detection of erosions.” 

Moderate consensus supported a cutoff of at least 2 mm for erosions when using MSUS for diagnostic purposes. 

Strong consensus supported using MSUS of the wrist, second and third metacarpophalangeal (MCP) joints, and second and third interphalangeal (PIP) joints to aid early RA diagnosis, with moderate consensus that cutoffs of least 2 grayscale (GS) or at least 1 GS with at least 1 power Doppler (PD) at the joint level supports both an RA diagnosis and, in patients already diagnosed with RA, a positive joint.

“Grayscale-only definitions were included since equipment may not have sensitive Doppler,” Kaeley said.

Strong consensus supported scanning only a reduced set of representative or symptomatic joints to monitor disease activity with MSUS. 

 

Inflammatory Signs, Disease Progression, and Flares

There was also strong consensus for using MSUS in patients with established RA and comorbidities to help distinguish between RA-related inflammation versus inflammation from other conditions, such as gout or calcium pyrophosphate deposition disease, or versus non–RA-related pain, such as that from fibromyalgia. 

Patients with fibromyalgia, for example, “tend to have more steroid exposure and a high prevalence of biologic use because the composite disease scores tend to overestimate disease activity, especially when compared to ultrasound assessment,” Kaeley said.

Moderate consensus supported using MSUS in patients with established RA to objectively evaluate inflammation so as to eliminate age-related bias.

While MSUS signs of synovitis had only moderate consensus to be associated with radiographic progression and decline in patient-reported outcomes for patients with early RA, consensus was strong for this association in patients with established RA.

In terms of predicting disease progression with MSUS monitoring of RA disease activity, moderate consensus supported scanning the wrists and MCPs and PIPs of the hands and using the dorsal view. Kaeley emphasized that ultrasound is a clinical tool that should be used to answer a clinical question, so the sonographer or clinician needs to provide guidance on the areas to be scanned. 

Multiple standardized scoring systems exist for predicting RA disease progression, but there is no consensus on which is the most effective, and there is only moderate consensus about the validity of using dichotomous scoring with an established cutoff for a positive joint.

The combination of MSUS with clinical examination appears to be more effective at confirming RA flares than using only clinical examination, and in certain patients with established RA, MSUS may provide insights into subclinical disease activity to help maintain remission and/or potentially guide treatment decisions, “especially when coming across de-escalation therapy decisions,” Kaeley said.

Despite the negative results of treat-to-target trials that tested MSUS as a routine tool in all patients, the committee achieved strong consensus on the potential value of using MSUS in early RA to clarify clinical status and/or help achieve low disease activity or remission in certain patient populations, “such as those with patient/provider discordance or difficult physical examinations,” Kaeley said. 

 

Therapy Response, Remission, and Shared Decision-Making

Moderate consensus supported acknowledgment that using MSUS to assess response to therapy could be affected by obesity and that MSUS can distinguish active synovitis symptoms from other pain sources in difficult-to-treat RA.

In patients with established RA, the feasibility of scanning the wrists, MCPs, PIPs, and relevant symptomatic joints for remission evaluation received moderate consensus. Meanwhile, strong consensus supported the idea that increasing the number of joints scanned with MSUS could increase the certainty of the patient having achieved remission, though the guidance acknowledges that “this must be balanced against the feasibility within the context of clinical care.” 

For confirming RA remission via MSUS, strong consensus supported using GS and PD synovitis and tenosynovitis findings. But consensus was moderate for using the combination of no PD signal and minimal synovial hypertrophy to define ultrasonographic remission and for the use of MSUS detection of subclinical inflammation to predict higher flare rates for those in clinical remission.

The committee moderately agreed that MSUS can enhance patient engagement and understanding of their disease to support personalized treatment decisions, such as adjusting disease-modifying antirheumatic drug regimens.

Finally, the committee broadly agreed that “the integration of musculoskeletal ultrasound presents significant advantages in shared decision-making between healthcare providers and patients,” Kaeley said. “Ultrasound, especially with Doppler technique, provides critical insights into disease activity and structural changes not always apparent during standard examination.” 

Arnold said she particularly appreciated that the committee, rather than prescribing a specific exam, opted to be more generalizable so that people use the guidance in the context that makes the most sense for them clinically. She said it’s an incredible tool, without excluding the importance of a patient’s labs and physical examination. 

“It’s helped us make diagnoses in patients who were difficult to diagnose. It’s helped us to understand response to therapy or no response to therapy,” she said. “It makes me question all the studies that I see done on medications where they’re not looking at some type of advanced imaging.” 

No external funding was noted for the development of the guidance. Ranganath has reported receiving research support from Bristol-Myers Squibb and Mallinckrodt. Kaeley has reported receiving research funding from AbbVie, Bristol-Myers Squibb, Gilead/Galapagos, Janssen, and Novartis. Arnold had no disclosures.

A version of this article first appeared on Medscape.com.

WASHINGTON — After more than a decade, the American College of Rheumatology has developed new draft guidance for the use of musculoskeletal ultrasound (MSUS) to help with diagnosis, monitoring, and prognosis of rheumatoid arthritis (RA). Though not yet finalized, the statements that came out of a first round of committee voting were unveiled at the annual meeting of the American College of Rheumatology (ACR).

The committee was charged with updating the 2012 recommendations on using MSUS in rheumatology clinical practice, explained Veena K. Ranganath, MD, professor of clinical medicine at the University of California, Los Angeles, and director of their Rheumatology Fellowship Musculoskeletal Ultrasound Training Program. 

More than 30,000 articles on MSUS and any arthritis have been published since 2012, and there have been significant advances and improvements in technology as well as more widespread education and use in rheumatologic clinical practice, Ranganath said. 

“There’s also been advancements in therapeutic agents and therapeutic strategies in use of these medications in rheumatoid arthritis,” Ranganath said. “We all know that the patient of today is very different than the patient of 10 years ago or 20 years ago, so this really impacts the clinical questions we ask of how we need to incorporate musculoskeletal ultrasound into our rheumatology clinical practice.” 

The process of developing the guidance involved determining key domains and then relevant clinical questions for ultrasonography using the PICO model (patient/population, intervention, comparison, and outcomes). Evidence came from a review of relevant literature published since 1993 in PubMed, Embase, and the Cochrane Database. A panel of 11 experts voted on the quality of the evidence as being moderate or strong for 33 statements, rejecting three that had no consensus. The committee will hold another round of voting before the guidance is published.

Erin Arnold, MD, a rheumatologist at Arnold Arthritis & Rheumatology in Skokie, Illinois, said in an interview she believes the new guidance will be “tremendously helpful,” particularly in getting “everybody on the same page” with similar practices and helping enhance diagnosis and response to therapy. 

Having used MSUS for over 20 years, Arnold said watching it evolve and seeing “this type of manuscript being put together as a resource for physicians who are taking care of inflammatory arthritis is exciting.”

“There’s not a single way we really can assess disease activity in our patients, and so having a composite of things that you’re looking at really enhances our ability to understand people’s pain,” Arnold said. 

“When you have a patient in front of you that is in so much pain but doesn’t have any active inflammation, it’s hard to want to further put them at risk with more medication,” she said. “It’s so meaningful to be able to have a conversation about ... what are other complementary interventions? How are they sleeping? How are they eating? What are they taking as far as supplements? What are they doing to decrease that kind of fear and fight-or-flight response that often can drive some of our pain?” 

 

Use of MSUS for Diagnosis Confirmation and Treatment Decisions

Gurjit S. Kaeley, MBBS, professor of medicine, division chief of rheumatology and clinical immunology, and medical director of the Musculoskeletal Ultrasound Program at the University of Florida College of Medicine, Jacksonville, reviewed the final statements for MSUS use with RA.

He said there was strong consensus that adding MSUS to clinical examination can aid diagnosis of early RA in patients with suspected RA, particularly with detection of synovitis, tenosynovitis, and erosions. There was moderate consensus that MSUS detection of tenosynovitis could predict later development of RA. 

“Furthermore, erosions do have a predictive prognostic value in telling us that these patients need more attention and more urgent attention to getting urgent care with disease-modifying medications,” Kaeley said. “Ultrasound scanning for bone erosions on a few target joints was found to be feasible in literature and provides information not available with clinical examination. Furthermore, ultrasound is more sensitive than plain radiography for the detection of erosions.” 

Moderate consensus supported a cutoff of at least 2 mm for erosions when using MSUS for diagnostic purposes. 

Strong consensus supported using MSUS of the wrist, second and third metacarpophalangeal (MCP) joints, and second and third interphalangeal (PIP) joints to aid early RA diagnosis, with moderate consensus that cutoffs of least 2 grayscale (GS) or at least 1 GS with at least 1 power Doppler (PD) at the joint level supports both an RA diagnosis and, in patients already diagnosed with RA, a positive joint.

“Grayscale-only definitions were included since equipment may not have sensitive Doppler,” Kaeley said.

Strong consensus supported scanning only a reduced set of representative or symptomatic joints to monitor disease activity with MSUS. 

 

Inflammatory Signs, Disease Progression, and Flares

There was also strong consensus for using MSUS in patients with established RA and comorbidities to help distinguish between RA-related inflammation versus inflammation from other conditions, such as gout or calcium pyrophosphate deposition disease, or versus non–RA-related pain, such as that from fibromyalgia. 

Patients with fibromyalgia, for example, “tend to have more steroid exposure and a high prevalence of biologic use because the composite disease scores tend to overestimate disease activity, especially when compared to ultrasound assessment,” Kaeley said.

Moderate consensus supported using MSUS in patients with established RA to objectively evaluate inflammation so as to eliminate age-related bias.

While MSUS signs of synovitis had only moderate consensus to be associated with radiographic progression and decline in patient-reported outcomes for patients with early RA, consensus was strong for this association in patients with established RA.

In terms of predicting disease progression with MSUS monitoring of RA disease activity, moderate consensus supported scanning the wrists and MCPs and PIPs of the hands and using the dorsal view. Kaeley emphasized that ultrasound is a clinical tool that should be used to answer a clinical question, so the sonographer or clinician needs to provide guidance on the areas to be scanned. 

Multiple standardized scoring systems exist for predicting RA disease progression, but there is no consensus on which is the most effective, and there is only moderate consensus about the validity of using dichotomous scoring with an established cutoff for a positive joint.

The combination of MSUS with clinical examination appears to be more effective at confirming RA flares than using only clinical examination, and in certain patients with established RA, MSUS may provide insights into subclinical disease activity to help maintain remission and/or potentially guide treatment decisions, “especially when coming across de-escalation therapy decisions,” Kaeley said.

Despite the negative results of treat-to-target trials that tested MSUS as a routine tool in all patients, the committee achieved strong consensus on the potential value of using MSUS in early RA to clarify clinical status and/or help achieve low disease activity or remission in certain patient populations, “such as those with patient/provider discordance or difficult physical examinations,” Kaeley said. 

 

Therapy Response, Remission, and Shared Decision-Making

Moderate consensus supported acknowledgment that using MSUS to assess response to therapy could be affected by obesity and that MSUS can distinguish active synovitis symptoms from other pain sources in difficult-to-treat RA.

In patients with established RA, the feasibility of scanning the wrists, MCPs, PIPs, and relevant symptomatic joints for remission evaluation received moderate consensus. Meanwhile, strong consensus supported the idea that increasing the number of joints scanned with MSUS could increase the certainty of the patient having achieved remission, though the guidance acknowledges that “this must be balanced against the feasibility within the context of clinical care.” 

For confirming RA remission via MSUS, strong consensus supported using GS and PD synovitis and tenosynovitis findings. But consensus was moderate for using the combination of no PD signal and minimal synovial hypertrophy to define ultrasonographic remission and for the use of MSUS detection of subclinical inflammation to predict higher flare rates for those in clinical remission.

The committee moderately agreed that MSUS can enhance patient engagement and understanding of their disease to support personalized treatment decisions, such as adjusting disease-modifying antirheumatic drug regimens.

Finally, the committee broadly agreed that “the integration of musculoskeletal ultrasound presents significant advantages in shared decision-making between healthcare providers and patients,” Kaeley said. “Ultrasound, especially with Doppler technique, provides critical insights into disease activity and structural changes not always apparent during standard examination.” 

Arnold said she particularly appreciated that the committee, rather than prescribing a specific exam, opted to be more generalizable so that people use the guidance in the context that makes the most sense for them clinically. She said it’s an incredible tool, without excluding the importance of a patient’s labs and physical examination. 

“It’s helped us make diagnoses in patients who were difficult to diagnose. It’s helped us to understand response to therapy or no response to therapy,” she said. “It makes me question all the studies that I see done on medications where they’re not looking at some type of advanced imaging.” 

No external funding was noted for the development of the guidance. Ranganath has reported receiving research support from Bristol-Myers Squibb and Mallinckrodt. Kaeley has reported receiving research funding from AbbVie, Bristol-Myers Squibb, Gilead/Galapagos, Janssen, and Novartis. Arnold had no disclosures.

A version of this article first appeared on Medscape.com.

WASHINGTON — Patients with granulomatosis with polyangiitis (GPA) completely tapered off prednisone have a more than fourfold risk of relapse by 6 months, compared with those tapered to 5 mg/day of prednisone; however, this benefit was only seen in patients not on rituximab, according to new research presented at the annual meeting of the American College of Rheumatology (ACR).

“For patients treated with rituximab, fully tapering off glucocorticoids is reasonable to consider as the first approach,” said Peter Merkel, MD, MPH, chief of the division of rheumatology at the University of Pennsylvania, Philadelphia, during his presentation of the findings.

Although a low dose of glucocorticoids can prevent some minor relapses in patients on other treatment regimens such as methotrexate or azathioprine, “fully tapering off prednisone presents relatively little risk of major relapse, and that major relapse can be treated rather quickly,” Merkel added.

The Assessment of Prednisone in Remission (TAPIR) trial enrolled 143 patients with GPA who were in remission (defined as a Birmingham Vasculitis Activity Score for Wegener’s Granulomatosis [BVAS/WG] of 0) within 1 year of treatment to induce remission for active disease and who were taking 5-10 mg of prednisone per day. After all patients tapered to 5 mg/day of prednisone, 71 patients completely tapered off prednisone over 4 weeks and remained off glucocorticoids until month 6. The remaining patients maintained a 5-mg/day dose over the study period. Placement in either treatment group was randomized, and patients continued other immunosuppressive therapy during the study.

Researchers evaluated the rate of relapse by 6 months, defined as a physician’s decision to increase the dose of glucocorticoids to treat GPA, in both groups.

Across all participants, the median age was 58 years, and 52% of patients were male. Most patients were White, and 47% of all patients were prescribed rituximab. 

At 6 months, 15.5% of participants who completely tapered off prednisone experienced a relapse of GPA, compared with 4.2% of those taking low-dose prednisone. Time to relapse was also shorter in the 0-mg prednisone group (P = .026), and relapses occurred continually over 6 months, Merkel said.

When stratified by rituximab use, relapse rates at 6 months between the 5-mg and 0-mg prednisone groups in patients taking rituximab showed no difference. Among patients not taking rituximab, those who completely stopped prednisone were nine and a half times as likely to experience relapse as those in the low-dose group. 

Despite these differences in relapse rates, “surprisingly, there were no differences in patient-reported outcomes [such as pain interference, physical function, and fatigue],” Merkel said. 

Across all patients, all but one relapse was characterized as minor. There were five serious adverse events and 10 infections in the 0-mg group versus one adverse event and 4 infections in the 5-mg group, but these differences were not statistically significant. 

In patients who relapsed, musculoskeletal and ear, nose, and throat manifestations of GPA were most common, and these are “the kind of stuff we see that is helped by low-dose glucocorticoids,” Merkel said.

It’s a good sign that for patients who were completely weaned off glucocorticoids, nearly all relapses were minor, Galina Marder, MD, a rheumatologist and associate professor of medicine at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, said in an interview. She was not involved with the research. 

The study “can reinforce the message [of] trying to get them off steroids completely [when possible],” she said.

The findings also provide insight for future clinical trials, Merkel noted. For patients taking non–rituximab-based regimens, completely tapering off glucocorticoids or maintaining a low dose can affect study outcomes.

“[These data are] even more important for clinical trials because they are [reinforcing] the fact that you can have a diminishing signal if you allow some patients to stay on 5 mg prednisone” when GPA flares are the primary outcome, Marder added.

The Vasculitis Clinical Research Consortium received funding for this research through grants from the National Institutes of Health. Merkel has disclosed financial relationships with AbbVie/Abbott, Amgen, argenx, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Cabaletta, ChemoCentryx, CSL Behring, Dynacure, Eicos, Electra, EMD Serono, Forbius, Genentech/Roche, Genzyme/Sanofi, GSK, HI-Bio, Inmagene, InflaRx, Janssen, Kiniksa, Kyverna, Magenta, MiroBio, Neutrolis, Novartis, NS Pharma, Pfizer, Regeneron, Sanofi, Sparrow, Takeda, Talaris, UpToDate, and Visterra. Marder consults for Amgen and Boehringer Ingelheim.

A version of this article first appeared on Medscape.com.

WASHINGTON — Patients with granulomatosis with polyangiitis (GPA) completely tapered off prednisone have a more than fourfold risk of relapse by 6 months, compared with those tapered to 5 mg/day of prednisone; however, this benefit was only seen in patients not on rituximab, according to new research presented at the annual meeting of the American College of Rheumatology (ACR).

“For patients treated with rituximab, fully tapering off glucocorticoids is reasonable to consider as the first approach,” said Peter Merkel, MD, MPH, chief of the division of rheumatology at the University of Pennsylvania, Philadelphia, during his presentation of the findings.

Although a low dose of glucocorticoids can prevent some minor relapses in patients on other treatment regimens such as methotrexate or azathioprine, “fully tapering off prednisone presents relatively little risk of major relapse, and that major relapse can be treated rather quickly,” Merkel added.

The Assessment of Prednisone in Remission (TAPIR) trial enrolled 143 patients with GPA who were in remission (defined as a Birmingham Vasculitis Activity Score for Wegener’s Granulomatosis [BVAS/WG] of 0) within 1 year of treatment to induce remission for active disease and who were taking 5-10 mg of prednisone per day. After all patients tapered to 5 mg/day of prednisone, 71 patients completely tapered off prednisone over 4 weeks and remained off glucocorticoids until month 6. The remaining patients maintained a 5-mg/day dose over the study period. Placement in either treatment group was randomized, and patients continued other immunosuppressive therapy during the study.

Researchers evaluated the rate of relapse by 6 months, defined as a physician’s decision to increase the dose of glucocorticoids to treat GPA, in both groups.

Across all participants, the median age was 58 years, and 52% of patients were male. Most patients were White, and 47% of all patients were prescribed rituximab. 

At 6 months, 15.5% of participants who completely tapered off prednisone experienced a relapse of GPA, compared with 4.2% of those taking low-dose prednisone. Time to relapse was also shorter in the 0-mg prednisone group (P = .026), and relapses occurred continually over 6 months, Merkel said.

When stratified by rituximab use, relapse rates at 6 months between the 5-mg and 0-mg prednisone groups in patients taking rituximab showed no difference. Among patients not taking rituximab, those who completely stopped prednisone were nine and a half times as likely to experience relapse as those in the low-dose group. 

Despite these differences in relapse rates, “surprisingly, there were no differences in patient-reported outcomes [such as pain interference, physical function, and fatigue],” Merkel said. 

Across all patients, all but one relapse was characterized as minor. There were five serious adverse events and 10 infections in the 0-mg group versus one adverse event and 4 infections in the 5-mg group, but these differences were not statistically significant. 

In patients who relapsed, musculoskeletal and ear, nose, and throat manifestations of GPA were most common, and these are “the kind of stuff we see that is helped by low-dose glucocorticoids,” Merkel said.

It’s a good sign that for patients who were completely weaned off glucocorticoids, nearly all relapses were minor, Galina Marder, MD, a rheumatologist and associate professor of medicine at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, said in an interview. She was not involved with the research. 

The study “can reinforce the message [of] trying to get them off steroids completely [when possible],” she said.

The findings also provide insight for future clinical trials, Merkel noted. For patients taking non–rituximab-based regimens, completely tapering off glucocorticoids or maintaining a low dose can affect study outcomes.

“[These data are] even more important for clinical trials because they are [reinforcing] the fact that you can have a diminishing signal if you allow some patients to stay on 5 mg prednisone” when GPA flares are the primary outcome, Marder added.

The Vasculitis Clinical Research Consortium received funding for this research through grants from the National Institutes of Health. Merkel has disclosed financial relationships with AbbVie/Abbott, Amgen, argenx, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Cabaletta, ChemoCentryx, CSL Behring, Dynacure, Eicos, Electra, EMD Serono, Forbius, Genentech/Roche, Genzyme/Sanofi, GSK, HI-Bio, Inmagene, InflaRx, Janssen, Kiniksa, Kyverna, Magenta, MiroBio, Neutrolis, Novartis, NS Pharma, Pfizer, Regeneron, Sanofi, Sparrow, Takeda, Talaris, UpToDate, and Visterra. Marder consults for Amgen and Boehringer Ingelheim.

A version of this article first appeared on Medscape.com.

WASHINGTON — Patients with granulomatosis with polyangiitis (GPA) completely tapered off prednisone have a more than fourfold risk of relapse by 6 months, compared with those tapered to 5 mg/day of prednisone; however, this benefit was only seen in patients not on rituximab, according to new research presented at the annual meeting of the American College of Rheumatology (ACR).

“For patients treated with rituximab, fully tapering off glucocorticoids is reasonable to consider as the first approach,” said Peter Merkel, MD, MPH, chief of the division of rheumatology at the University of Pennsylvania, Philadelphia, during his presentation of the findings.

Although a low dose of glucocorticoids can prevent some minor relapses in patients on other treatment regimens such as methotrexate or azathioprine, “fully tapering off prednisone presents relatively little risk of major relapse, and that major relapse can be treated rather quickly,” Merkel added.

The Assessment of Prednisone in Remission (TAPIR) trial enrolled 143 patients with GPA who were in remission (defined as a Birmingham Vasculitis Activity Score for Wegener’s Granulomatosis [BVAS/WG] of 0) within 1 year of treatment to induce remission for active disease and who were taking 5-10 mg of prednisone per day. After all patients tapered to 5 mg/day of prednisone, 71 patients completely tapered off prednisone over 4 weeks and remained off glucocorticoids until month 6. The remaining patients maintained a 5-mg/day dose over the study period. Placement in either treatment group was randomized, and patients continued other immunosuppressive therapy during the study.

Researchers evaluated the rate of relapse by 6 months, defined as a physician’s decision to increase the dose of glucocorticoids to treat GPA, in both groups.

Across all participants, the median age was 58 years, and 52% of patients were male. Most patients were White, and 47% of all patients were prescribed rituximab. 

At 6 months, 15.5% of participants who completely tapered off prednisone experienced a relapse of GPA, compared with 4.2% of those taking low-dose prednisone. Time to relapse was also shorter in the 0-mg prednisone group (P = .026), and relapses occurred continually over 6 months, Merkel said.

When stratified by rituximab use, relapse rates at 6 months between the 5-mg and 0-mg prednisone groups in patients taking rituximab showed no difference. Among patients not taking rituximab, those who completely stopped prednisone were nine and a half times as likely to experience relapse as those in the low-dose group. 

Despite these differences in relapse rates, “surprisingly, there were no differences in patient-reported outcomes [such as pain interference, physical function, and fatigue],” Merkel said. 

Across all patients, all but one relapse was characterized as minor. There were five serious adverse events and 10 infections in the 0-mg group versus one adverse event and 4 infections in the 5-mg group, but these differences were not statistically significant. 

In patients who relapsed, musculoskeletal and ear, nose, and throat manifestations of GPA were most common, and these are “the kind of stuff we see that is helped by low-dose glucocorticoids,” Merkel said.

It’s a good sign that for patients who were completely weaned off glucocorticoids, nearly all relapses were minor, Galina Marder, MD, a rheumatologist and associate professor of medicine at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, said in an interview. She was not involved with the research. 

The study “can reinforce the message [of] trying to get them off steroids completely [when possible],” she said.

The findings also provide insight for future clinical trials, Merkel noted. For patients taking non–rituximab-based regimens, completely tapering off glucocorticoids or maintaining a low dose can affect study outcomes.

“[These data are] even more important for clinical trials because they are [reinforcing] the fact that you can have a diminishing signal if you allow some patients to stay on 5 mg prednisone” when GPA flares are the primary outcome, Marder added.

The Vasculitis Clinical Research Consortium received funding for this research through grants from the National Institutes of Health. Merkel has disclosed financial relationships with AbbVie/Abbott, Amgen, argenx, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Cabaletta, ChemoCentryx, CSL Behring, Dynacure, Eicos, Electra, EMD Serono, Forbius, Genentech/Roche, Genzyme/Sanofi, GSK, HI-Bio, Inmagene, InflaRx, Janssen, Kiniksa, Kyverna, Magenta, MiroBio, Neutrolis, Novartis, NS Pharma, Pfizer, Regeneron, Sanofi, Sparrow, Takeda, Talaris, UpToDate, and Visterra. Marder consults for Amgen and Boehringer Ingelheim.

A version of this article first appeared on Medscape.com.

WASHINGTON — The B cell–depleting agent inebilizumab (Uplizna) dramatically reduced the risk of flares and increased year-long remission of IgG4-related disease (RD), new research has found.

In a phase 3, multicenter, double-blind, randomized, placebo-controlled trial of 135 adults with active IgG4-RD, treatment with inebilizumab resulted in a significant 87% reduction in flare risk and nearly fivefold greater likelihood of flare-free remission at 1 year. The results were published online November 14 in The New England Journal of Medicine and were presented at the annual meeting of the American College of Rheumatology (ACR).

The drug’s manufacturer, Amgen, released top-line results of the trial, called MITIGATE, in June 2024.

 

Until now, the mainstay of management for the chronic multiorgan disease IgG4-RD has been glucocorticoids, which can cause numerous adverse effects. “It is hoped that inebilizumab can be used as an important steroid-sparing medication in this disease to reduce steroid toxicity,” lead author John H. Stone, MD, professor of medicine at Harvard Medical School, Boston, Massachusetts, said in an interview, noting that it may not entirely eliminate the need for steroid treatment, but for many, it appears to work after the remission induction period as a monotherapy without steroids. 

Asked to comment, Leonard H. Calabrese, DO, head of the Section of Clinical Immunology and manager of the Clinical Immunology Clinic at the Cleveland Clinic, Ohio, said: “There has been anecdotal or observational evidence for some effect with other immunosuppressive agents, including rituximab, but no robust clinical trial until this study. This clearly has demonstrated efficacy by reducing the risk of flares. And most importantly, putting people into remission means no active disease in any given organ. ... This gives us another tool in the toolbox to attack B cell–directed diseases, and I think it really makes a lot of sense.”

Calabrese cautioned, though, that “this is a disease that extends over many years. This is just a 1-year study. Label extensions will be important.”

 

And several questions remain, Calabrese noted: “How long do patients need to remain on drug? What will happen when the drug is stopped? Can they be retreated? These are the natural questions that arise in any sentinel study like this. But this is extremely encouraging. And I think it’s great for patients. I also think it’s a clarion call to increase awareness about this disease since there’s now strong evidence of effective treatment.” 

 

Underrecognized, Often Misdiagnosed as Cancer

Indeed, IgG4-RD, a chronic, relapsing, autoimmune, fibro-inflammatory multiorgan disease, was only first described in Japan in 2003. Since then, it has been reported all over the world yet remains vastly underrecognized. It is often misdiagnosed as cancer because it produces lesions in multiple organs. It received an ICD-10 code only about a year ago. A previous study estimated a prevalence of about 5.3 persons per 100,000 but that is likely to be a three- to fourfold underestimate, said Stone, who is also executive chairman of the IgG4ward! Foundation. 

“Nobody had heard of the disease until about 20 years ago. ... And there are many people in the world who have still not heard of it despite the fact that it is a multiorgan autoimmune disease and is probably as common, or more common, than many other diseases that rheumatologists spend a lot of time thinking about, such as scleroderma.”

While knowledge about the disease is increasing in rheumatology circles, it’s less well-recognized among many of the specialties where patients present, depending on the location of their lesions. These include gastroenterology, ophthalmology, pulmonary medicine, neurology, and nephrology. “All would be likely to see this disease,” Stone said. 

The disease can be mistaken for tumors in many of those locations and even as metastatic cancer, he noted, adding that “any time a patient has a mass lesion in a typical organ, the pancreas, the major salivary glands, the lungs, or the kidneys, this should be on the differential diagnosis.” 

The diagnosis of IgG4-RD is a clinical one, involving “quadrangulation between clinical features, serological findings, IgG4 levels in the blood, radiology studies, and then pathology biopsies when those are available,” Stone said. 

Calabrese characterized the current situation as “we’re all blind men on the elephant. To the neurologist or the neurosurgeon, it’s a mass in the brain. It could present to the ophthalmologist as an [eye] tumor. It can be thyroid gland failure, pulmonary disease, retroperitoneal fibrosis, hepatobiliary disease, and beyond. So, whoever sees that patient, there’s often a long lag time in recognizing it.”

And interestingly, Stone noted that unlike other autoimmune diseases, IgG4-RD primarily affects middle-aged men rather than younger-to-middle-aged women. And when IgG4-RD is diagnosed, glucocorticoid treatment can be particularly toxic when the pancreas is involved, heightening the risk for hyperglycemia and potentially causing diabetes. 

 

Dramatic Improvement in Flares, Remission Achievement

MITIGATE is a phase 3, multicenter, double-blind, randomized, placebo-controlled trial in which 135 adults (mean age 58.2 years, 88 men) with active IgG4-RD were randomized 1:1 to receive 300-mg intravenous infusions of inebilizumab or placebo on days 1 and 15, and again at week 26. At baseline, 62 (45.9%) participants had newly diagnosed IgG4-RD and 73 (54.1%) had recurrent disease. 

Both groups received identical glucocorticoid tapers. Overall, 127 (94.1%) completed the 52 weeks of treatment. 

By 52 weeks, only seven patients in the inebilizumab group (10%) had experienced disease flares vs 40 (60%) in the placebo group, a significant difference with a hazard ratio of 0.13 (P < .001). 

The percentage of participants achieving flare-free, treatment-free complete remission was 59 with inebilizumab (57%), compared with just 15 (22%) in the placebo group (odds ratio [OR], 4.68; P < .001). And for flare-free, glucocorticoid-free complete remission, those proportions were 40 (59%) vs 15 (22%), respectively (OR, 4.96; P < .001). 

Excluding the 8-week glucocorticoid taper period, mean total glucocorticoid use was 1264.2 mg less in the inebilizumab than the placebo group, a significant reduction. Overall, 61 participants (90%) were able to entirely discontinue glucocorticoids during the trial, compared with just 25 (37%) in the placebo group. 

Adverse events of grade 3 or higher occurred in 12 participants (18%) in the inebilizumab group and 8 (12%) in the placebo group; serious adverse events occurred in 12 (18%) and 6 (9%), respectively. However, no serious adverse event occurred in more than one participant, and there were no deaths. Adverse events led to withdrawal from the trial in six patients (9%) in the inebilizumab group and three patients (4%) in the placebo group. 

Adverse events that occurred in more than 10% of participants in the inebilizumab group were COVID-19 in 16 participants (24%), lymphopenia in 11 (16%), and urinary tract infection in 8 (12%). 

Importantly, Stone noted, B-cell depletion can reduce responses to vaccines, so patients should receive all recommended vaccinations, including COVID-19, influenza, respiratory syncytial virus, and others, prior to initiating therapy. 

Uplizna (inebilizumab-cdon) was approved by the Food and Drug Administration (FDA) for the treatment of neuromyelitis optica spectrum disorder in 2020. In October 2024, the FDA granted Amgen breakthrough therapy designation for use in IgG4-RD. The company is also developing the drug for use in myasthenia gravis.

The study was funded by Amgen. Stone has reported being a consultant for Amgen, Zenas, Argenx, Bristol Myers Squibb, Novartis, Sanofi, and Horizon Pharma. Calabrese has reported being a consultant and/or speaker for Amgen, AstraZeneca, Jansen, Sanofi, and UCB.

A version of this article first appeared on Medscape.com.

WASHINGTON — The B cell–depleting agent inebilizumab (Uplizna) dramatically reduced the risk of flares and increased year-long remission of IgG4-related disease (RD), new research has found.

In a phase 3, multicenter, double-blind, randomized, placebo-controlled trial of 135 adults with active IgG4-RD, treatment with inebilizumab resulted in a significant 87% reduction in flare risk and nearly fivefold greater likelihood of flare-free remission at 1 year. The results were published online November 14 in The New England Journal of Medicine and were presented at the annual meeting of the American College of Rheumatology (ACR).

The drug’s manufacturer, Amgen, released top-line results of the trial, called MITIGATE, in June 2024.

 

Until now, the mainstay of management for the chronic multiorgan disease IgG4-RD has been glucocorticoids, which can cause numerous adverse effects. “It is hoped that inebilizumab can be used as an important steroid-sparing medication in this disease to reduce steroid toxicity,” lead author John H. Stone, MD, professor of medicine at Harvard Medical School, Boston, Massachusetts, said in an interview, noting that it may not entirely eliminate the need for steroid treatment, but for many, it appears to work after the remission induction period as a monotherapy without steroids. 

Asked to comment, Leonard H. Calabrese, DO, head of the Section of Clinical Immunology and manager of the Clinical Immunology Clinic at the Cleveland Clinic, Ohio, said: “There has been anecdotal or observational evidence for some effect with other immunosuppressive agents, including rituximab, but no robust clinical trial until this study. This clearly has demonstrated efficacy by reducing the risk of flares. And most importantly, putting people into remission means no active disease in any given organ. ... This gives us another tool in the toolbox to attack B cell–directed diseases, and I think it really makes a lot of sense.”

Calabrese cautioned, though, that “this is a disease that extends over many years. This is just a 1-year study. Label extensions will be important.”

 

And several questions remain, Calabrese noted: “How long do patients need to remain on drug? What will happen when the drug is stopped? Can they be retreated? These are the natural questions that arise in any sentinel study like this. But this is extremely encouraging. And I think it’s great for patients. I also think it’s a clarion call to increase awareness about this disease since there’s now strong evidence of effective treatment.” 

 

Underrecognized, Often Misdiagnosed as Cancer

Indeed, IgG4-RD, a chronic, relapsing, autoimmune, fibro-inflammatory multiorgan disease, was only first described in Japan in 2003. Since then, it has been reported all over the world yet remains vastly underrecognized. It is often misdiagnosed as cancer because it produces lesions in multiple organs. It received an ICD-10 code only about a year ago. A previous study estimated a prevalence of about 5.3 persons per 100,000 but that is likely to be a three- to fourfold underestimate, said Stone, who is also executive chairman of the IgG4ward! Foundation. 

“Nobody had heard of the disease until about 20 years ago. ... And there are many people in the world who have still not heard of it despite the fact that it is a multiorgan autoimmune disease and is probably as common, or more common, than many other diseases that rheumatologists spend a lot of time thinking about, such as scleroderma.”

While knowledge about the disease is increasing in rheumatology circles, it’s less well-recognized among many of the specialties where patients present, depending on the location of their lesions. These include gastroenterology, ophthalmology, pulmonary medicine, neurology, and nephrology. “All would be likely to see this disease,” Stone said. 

The disease can be mistaken for tumors in many of those locations and even as metastatic cancer, he noted, adding that “any time a patient has a mass lesion in a typical organ, the pancreas, the major salivary glands, the lungs, or the kidneys, this should be on the differential diagnosis.” 

The diagnosis of IgG4-RD is a clinical one, involving “quadrangulation between clinical features, serological findings, IgG4 levels in the blood, radiology studies, and then pathology biopsies when those are available,” Stone said. 

Calabrese characterized the current situation as “we’re all blind men on the elephant. To the neurologist or the neurosurgeon, it’s a mass in the brain. It could present to the ophthalmologist as an [eye] tumor. It can be thyroid gland failure, pulmonary disease, retroperitoneal fibrosis, hepatobiliary disease, and beyond. So, whoever sees that patient, there’s often a long lag time in recognizing it.”

And interestingly, Stone noted that unlike other autoimmune diseases, IgG4-RD primarily affects middle-aged men rather than younger-to-middle-aged women. And when IgG4-RD is diagnosed, glucocorticoid treatment can be particularly toxic when the pancreas is involved, heightening the risk for hyperglycemia and potentially causing diabetes. 

 

Dramatic Improvement in Flares, Remission Achievement

MITIGATE is a phase 3, multicenter, double-blind, randomized, placebo-controlled trial in which 135 adults (mean age 58.2 years, 88 men) with active IgG4-RD were randomized 1:1 to receive 300-mg intravenous infusions of inebilizumab or placebo on days 1 and 15, and again at week 26. At baseline, 62 (45.9%) participants had newly diagnosed IgG4-RD and 73 (54.1%) had recurrent disease. 

Both groups received identical glucocorticoid tapers. Overall, 127 (94.1%) completed the 52 weeks of treatment. 

By 52 weeks, only seven patients in the inebilizumab group (10%) had experienced disease flares vs 40 (60%) in the placebo group, a significant difference with a hazard ratio of 0.13 (P < .001). 

The percentage of participants achieving flare-free, treatment-free complete remission was 59 with inebilizumab (57%), compared with just 15 (22%) in the placebo group (odds ratio [OR], 4.68; P < .001). And for flare-free, glucocorticoid-free complete remission, those proportions were 40 (59%) vs 15 (22%), respectively (OR, 4.96; P < .001). 

Excluding the 8-week glucocorticoid taper period, mean total glucocorticoid use was 1264.2 mg less in the inebilizumab than the placebo group, a significant reduction. Overall, 61 participants (90%) were able to entirely discontinue glucocorticoids during the trial, compared with just 25 (37%) in the placebo group. 

Adverse events of grade 3 or higher occurred in 12 participants (18%) in the inebilizumab group and 8 (12%) in the placebo group; serious adverse events occurred in 12 (18%) and 6 (9%), respectively. However, no serious adverse event occurred in more than one participant, and there were no deaths. Adverse events led to withdrawal from the trial in six patients (9%) in the inebilizumab group and three patients (4%) in the placebo group. 

Adverse events that occurred in more than 10% of participants in the inebilizumab group were COVID-19 in 16 participants (24%), lymphopenia in 11 (16%), and urinary tract infection in 8 (12%). 

Importantly, Stone noted, B-cell depletion can reduce responses to vaccines, so patients should receive all recommended vaccinations, including COVID-19, influenza, respiratory syncytial virus, and others, prior to initiating therapy. 

Uplizna (inebilizumab-cdon) was approved by the Food and Drug Administration (FDA) for the treatment of neuromyelitis optica spectrum disorder in 2020. In October 2024, the FDA granted Amgen breakthrough therapy designation for use in IgG4-RD. The company is also developing the drug for use in myasthenia gravis.

The study was funded by Amgen. Stone has reported being a consultant for Amgen, Zenas, Argenx, Bristol Myers Squibb, Novartis, Sanofi, and Horizon Pharma. Calabrese has reported being a consultant and/or speaker for Amgen, AstraZeneca, Jansen, Sanofi, and UCB.

A version of this article first appeared on Medscape.com.

WASHINGTON — The B cell–depleting agent inebilizumab (Uplizna) dramatically reduced the risk of flares and increased year-long remission of IgG4-related disease (RD), new research has found.

In a phase 3, multicenter, double-blind, randomized, placebo-controlled trial of 135 adults with active IgG4-RD, treatment with inebilizumab resulted in a significant 87% reduction in flare risk and nearly fivefold greater likelihood of flare-free remission at 1 year. The results were published online November 14 in The New England Journal of Medicine and were presented at the annual meeting of the American College of Rheumatology (ACR).

The drug’s manufacturer, Amgen, released top-line results of the trial, called MITIGATE, in June 2024.

 

Until now, the mainstay of management for the chronic multiorgan disease IgG4-RD has been glucocorticoids, which can cause numerous adverse effects. “It is hoped that inebilizumab can be used as an important steroid-sparing medication in this disease to reduce steroid toxicity,” lead author John H. Stone, MD, professor of medicine at Harvard Medical School, Boston, Massachusetts, said in an interview, noting that it may not entirely eliminate the need for steroid treatment, but for many, it appears to work after the remission induction period as a monotherapy without steroids. 

Asked to comment, Leonard H. Calabrese, DO, head of the Section of Clinical Immunology and manager of the Clinical Immunology Clinic at the Cleveland Clinic, Ohio, said: “There has been anecdotal or observational evidence for some effect with other immunosuppressive agents, including rituximab, but no robust clinical trial until this study. This clearly has demonstrated efficacy by reducing the risk of flares. And most importantly, putting people into remission means no active disease in any given organ. ... This gives us another tool in the toolbox to attack B cell–directed diseases, and I think it really makes a lot of sense.”

Calabrese cautioned, though, that “this is a disease that extends over many years. This is just a 1-year study. Label extensions will be important.”

 

And several questions remain, Calabrese noted: “How long do patients need to remain on drug? What will happen when the drug is stopped? Can they be retreated? These are the natural questions that arise in any sentinel study like this. But this is extremely encouraging. And I think it’s great for patients. I also think it’s a clarion call to increase awareness about this disease since there’s now strong evidence of effective treatment.” 

 

Underrecognized, Often Misdiagnosed as Cancer

Indeed, IgG4-RD, a chronic, relapsing, autoimmune, fibro-inflammatory multiorgan disease, was only first described in Japan in 2003. Since then, it has been reported all over the world yet remains vastly underrecognized. It is often misdiagnosed as cancer because it produces lesions in multiple organs. It received an ICD-10 code only about a year ago. A previous study estimated a prevalence of about 5.3 persons per 100,000 but that is likely to be a three- to fourfold underestimate, said Stone, who is also executive chairman of the IgG4ward! Foundation. 

“Nobody had heard of the disease until about 20 years ago. ... And there are many people in the world who have still not heard of it despite the fact that it is a multiorgan autoimmune disease and is probably as common, or more common, than many other diseases that rheumatologists spend a lot of time thinking about, such as scleroderma.”

While knowledge about the disease is increasing in rheumatology circles, it’s less well-recognized among many of the specialties where patients present, depending on the location of their lesions. These include gastroenterology, ophthalmology, pulmonary medicine, neurology, and nephrology. “All would be likely to see this disease,” Stone said. 

The disease can be mistaken for tumors in many of those locations and even as metastatic cancer, he noted, adding that “any time a patient has a mass lesion in a typical organ, the pancreas, the major salivary glands, the lungs, or the kidneys, this should be on the differential diagnosis.” 

The diagnosis of IgG4-RD is a clinical one, involving “quadrangulation between clinical features, serological findings, IgG4 levels in the blood, radiology studies, and then pathology biopsies when those are available,” Stone said. 

Calabrese characterized the current situation as “we’re all blind men on the elephant. To the neurologist or the neurosurgeon, it’s a mass in the brain. It could present to the ophthalmologist as an [eye] tumor. It can be thyroid gland failure, pulmonary disease, retroperitoneal fibrosis, hepatobiliary disease, and beyond. So, whoever sees that patient, there’s often a long lag time in recognizing it.”

And interestingly, Stone noted that unlike other autoimmune diseases, IgG4-RD primarily affects middle-aged men rather than younger-to-middle-aged women. And when IgG4-RD is diagnosed, glucocorticoid treatment can be particularly toxic when the pancreas is involved, heightening the risk for hyperglycemia and potentially causing diabetes. 

 

Dramatic Improvement in Flares, Remission Achievement

MITIGATE is a phase 3, multicenter, double-blind, randomized, placebo-controlled trial in which 135 adults (mean age 58.2 years, 88 men) with active IgG4-RD were randomized 1:1 to receive 300-mg intravenous infusions of inebilizumab or placebo on days 1 and 15, and again at week 26. At baseline, 62 (45.9%) participants had newly diagnosed IgG4-RD and 73 (54.1%) had recurrent disease. 

Both groups received identical glucocorticoid tapers. Overall, 127 (94.1%) completed the 52 weeks of treatment. 

By 52 weeks, only seven patients in the inebilizumab group (10%) had experienced disease flares vs 40 (60%) in the placebo group, a significant difference with a hazard ratio of 0.13 (P < .001). 

The percentage of participants achieving flare-free, treatment-free complete remission was 59 with inebilizumab (57%), compared with just 15 (22%) in the placebo group (odds ratio [OR], 4.68; P < .001). And for flare-free, glucocorticoid-free complete remission, those proportions were 40 (59%) vs 15 (22%), respectively (OR, 4.96; P < .001). 

Excluding the 8-week glucocorticoid taper period, mean total glucocorticoid use was 1264.2 mg less in the inebilizumab than the placebo group, a significant reduction. Overall, 61 participants (90%) were able to entirely discontinue glucocorticoids during the trial, compared with just 25 (37%) in the placebo group. 

Adverse events of grade 3 or higher occurred in 12 participants (18%) in the inebilizumab group and 8 (12%) in the placebo group; serious adverse events occurred in 12 (18%) and 6 (9%), respectively. However, no serious adverse event occurred in more than one participant, and there were no deaths. Adverse events led to withdrawal from the trial in six patients (9%) in the inebilizumab group and three patients (4%) in the placebo group. 

Adverse events that occurred in more than 10% of participants in the inebilizumab group were COVID-19 in 16 participants (24%), lymphopenia in 11 (16%), and urinary tract infection in 8 (12%). 

Importantly, Stone noted, B-cell depletion can reduce responses to vaccines, so patients should receive all recommended vaccinations, including COVID-19, influenza, respiratory syncytial virus, and others, prior to initiating therapy. 

Uplizna (inebilizumab-cdon) was approved by the Food and Drug Administration (FDA) for the treatment of neuromyelitis optica spectrum disorder in 2020. In October 2024, the FDA granted Amgen breakthrough therapy designation for use in IgG4-RD. The company is also developing the drug for use in myasthenia gravis.

The study was funded by Amgen. Stone has reported being a consultant for Amgen, Zenas, Argenx, Bristol Myers Squibb, Novartis, Sanofi, and Horizon Pharma. Calabrese has reported being a consultant and/or speaker for Amgen, AstraZeneca, Jansen, Sanofi, and UCB.

A version of this article first appeared on Medscape.com.