Lucy Hicks

WASHINGTON — The investigational anti-CD40 ligand agent dapirolizumab pegol (DZP) outperformed placebo in improving disease activity and reducing high-dose corticosteroid use in patients with systemic lupus erythematosus (SLE) in the phase 3 PHOENYCS GO trial.

“We really think that dapirolizumab pegol may represent a novel treatment for lupus, particularly given its broad immune modulatory effects,” 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 presented the study in a late-breaking poster session at the American College of Rheumatology (ACR) 2024 Annual Meeting.

There is a “huge unmet need” for drugs for lupus, Clowse told this news organization. Patients with SLE continue to have high disease burden, including ongoing symptoms often driven by inflammation. Corticosteroids are often the best medications to control disease activity, she said, but they can result in long-term toxicity.

 

What Makes DZP Unique?

Through CD40 ligand signaling, DZP has been shown to reduce B- and T-cell activation and to downregulate interferon pathways. Previous antibodies targeting the CD40 ligand have been associated with an increased risk for thromboembolic events. However, DZP lacks the Fc portion of the antibody, which can bind to platelets and cause clotting. Data from phase 1, 2, and 3 trials thus far do not show an elevated risk for these events, Clowse explained. In fact, safety signals were strong enough that patients with antiphospholipid antibodies — a key driver for blood clots in patients with SLE — were included in the trial.

In PHOENYCS GO, investigators enrolled 321 patients with moderate to severe SLE with persistently active or frequently flaring/relapsing-remitting disease activity despite stable standard of care (SOC) medications such as antimalarials, corticosteroids, and immunosuppressants.

Patients were randomized 2:1 to receive intravenous DZP (24 mg/kg) plus SOC or intravenous placebo plus SOC every 4 weeks, with patients and investigators blinded to treatment assignments.

Patients taking a corticosteroid dose > 7.5 mg/day began a mandatory steroid taper by week 8 of the trial, with the goal of reducing that to < 7.5 mg/day. The tapering regimen was at the discretion of providers and was adapted to each patient’s individual disease activity.

The primary endpoint was British Isles Lupus Assessment Group–based Composite Lupus Assessment (BICLA) response at week 48.

Patients in the DZP and placebo groups were on average 43.5 and 41.5 years old, respectively. More than 90% of patients were women, all on concomitant SLE medications. About half of the participants took a daily corticosteroid dose > 7.5 mg.

At 48 weeks, half of the DZP group (49.5%) achieved BICLA response compared with 34.6% in the placebo group (P = .0110). A higher proportion of patients taking DZP achieved SLE Responder Index-4 response than those taking placebo (60.1% vs 41.1%, respectively; P = .0014), and the rate of severe British Isles Lupus Assessment Group flares in the DZP group was half that of the placebo group (11.6% vs 23.4%; P = .0257). In the subgroup of patients who underwent corticosteroid tapering, 72.4% receiving DZP and 52.9% taking placebo reduced their dose to < 7.5 mg/day by 48 weeks (P = .0404).

DZP was generally well tolerated. Over 48 weeks, 82.6% of the DZP group and 75% of the placebo group reported treatment-emergent adverse events, but serious occurrences were more common in the placebo group (14.8%) than in the DZP group (9.9%). Herpes viral infections were higher in the placebo group, although there were three ophthalmic herpes cases in the DZP group. There was one case of acute myocardial infarction and one death linked to gangrene-related sepsis in patients receiving DZP.

 

A ‘Mild to Moderate’ Response

Although these are definitely positive results, they show a “mild to moderate response” to DZP, commented Gregory Gardner, MD, an emeritus professor in the Division of Rheumatology at the University of Washington, Seattle, and chair of the American College of Rheumatology’s annual meeting planning committee. He moderated the session where the research was presented. Although DZP showed efficacy among some patients, he noted, “there were still 51% patients that it didn’t work for.” 

The drug uses an alternative pathway to current lupus drugs, Gardner added, and more research is needed to understand how best to use this medication in practice.

Clowse noted that DZP could be particularly beneficial for patients with SLE who want to get pregnant. Many drugs used to treat the disease are teratogenic; however, “because of the lack of Fc portion on this drug, it very likely does not cross the placenta in any kind of significant amount,” she said. Although there are not yet any reproductive safety data on DZP, she added, “that is a great potential niche.”

Biogen and UCB, which are jointly developing DZP, aim to start a second phase 3 trial of DZP in patients with SLE, called PHOENYCS FLY, in 2024.

The trial was sponsored by UCB. Clowse is a consultant and has received grant/research support from GSK and UCB. Gardner had no relevant disclosures.

 

A version of this article appeared on Medscape.com.

WASHINGTON — The investigational anti-CD40 ligand agent dapirolizumab pegol (DZP) outperformed placebo in improving disease activity and reducing high-dose corticosteroid use in patients with systemic lupus erythematosus (SLE) in the phase 3 PHOENYCS GO trial.

“We really think that dapirolizumab pegol may represent a novel treatment for lupus, particularly given its broad immune modulatory effects,” 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 presented the study in a late-breaking poster session at the American College of Rheumatology (ACR) 2024 Annual Meeting.

There is a “huge unmet need” for drugs for lupus, Clowse told this news organization. Patients with SLE continue to have high disease burden, including ongoing symptoms often driven by inflammation. Corticosteroids are often the best medications to control disease activity, she said, but they can result in long-term toxicity.

 

What Makes DZP Unique?

Through CD40 ligand signaling, DZP has been shown to reduce B- and T-cell activation and to downregulate interferon pathways. Previous antibodies targeting the CD40 ligand have been associated with an increased risk for thromboembolic events. However, DZP lacks the Fc portion of the antibody, which can bind to platelets and cause clotting. Data from phase 1, 2, and 3 trials thus far do not show an elevated risk for these events, Clowse explained. In fact, safety signals were strong enough that patients with antiphospholipid antibodies — a key driver for blood clots in patients with SLE — were included in the trial.

In PHOENYCS GO, investigators enrolled 321 patients with moderate to severe SLE with persistently active or frequently flaring/relapsing-remitting disease activity despite stable standard of care (SOC) medications such as antimalarials, corticosteroids, and immunosuppressants.

Patients were randomized 2:1 to receive intravenous DZP (24 mg/kg) plus SOC or intravenous placebo plus SOC every 4 weeks, with patients and investigators blinded to treatment assignments.

Patients taking a corticosteroid dose > 7.5 mg/day began a mandatory steroid taper by week 8 of the trial, with the goal of reducing that to < 7.5 mg/day. The tapering regimen was at the discretion of providers and was adapted to each patient’s individual disease activity.

The primary endpoint was British Isles Lupus Assessment Group–based Composite Lupus Assessment (BICLA) response at week 48.

Patients in the DZP and placebo groups were on average 43.5 and 41.5 years old, respectively. More than 90% of patients were women, all on concomitant SLE medications. About half of the participants took a daily corticosteroid dose > 7.5 mg.

At 48 weeks, half of the DZP group (49.5%) achieved BICLA response compared with 34.6% in the placebo group (P = .0110). A higher proportion of patients taking DZP achieved SLE Responder Index-4 response than those taking placebo (60.1% vs 41.1%, respectively; P = .0014), and the rate of severe British Isles Lupus Assessment Group flares in the DZP group was half that of the placebo group (11.6% vs 23.4%; P = .0257). In the subgroup of patients who underwent corticosteroid tapering, 72.4% receiving DZP and 52.9% taking placebo reduced their dose to < 7.5 mg/day by 48 weeks (P = .0404).

DZP was generally well tolerated. Over 48 weeks, 82.6% of the DZP group and 75% of the placebo group reported treatment-emergent adverse events, but serious occurrences were more common in the placebo group (14.8%) than in the DZP group (9.9%). Herpes viral infections were higher in the placebo group, although there were three ophthalmic herpes cases in the DZP group. There was one case of acute myocardial infarction and one death linked to gangrene-related sepsis in patients receiving DZP.

 

A ‘Mild to Moderate’ Response

Although these are definitely positive results, they show a “mild to moderate response” to DZP, commented Gregory Gardner, MD, an emeritus professor in the Division of Rheumatology at the University of Washington, Seattle, and chair of the American College of Rheumatology’s annual meeting planning committee. He moderated the session where the research was presented. Although DZP showed efficacy among some patients, he noted, “there were still 51% patients that it didn’t work for.” 

The drug uses an alternative pathway to current lupus drugs, Gardner added, and more research is needed to understand how best to use this medication in practice.

Clowse noted that DZP could be particularly beneficial for patients with SLE who want to get pregnant. Many drugs used to treat the disease are teratogenic; however, “because of the lack of Fc portion on this drug, it very likely does not cross the placenta in any kind of significant amount,” she said. Although there are not yet any reproductive safety data on DZP, she added, “that is a great potential niche.”

Biogen and UCB, which are jointly developing DZP, aim to start a second phase 3 trial of DZP in patients with SLE, called PHOENYCS FLY, in 2024.

The trial was sponsored by UCB. Clowse is a consultant and has received grant/research support from GSK and UCB. Gardner had no relevant disclosures.

 

A version of this article appeared on Medscape.com.

WASHINGTON — The investigational anti-CD40 ligand agent dapirolizumab pegol (DZP) outperformed placebo in improving disease activity and reducing high-dose corticosteroid use in patients with systemic lupus erythematosus (SLE) in the phase 3 PHOENYCS GO trial.

“We really think that dapirolizumab pegol may represent a novel treatment for lupus, particularly given its broad immune modulatory effects,” 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 presented the study in a late-breaking poster session at the American College of Rheumatology (ACR) 2024 Annual Meeting.

There is a “huge unmet need” for drugs for lupus, Clowse told this news organization. Patients with SLE continue to have high disease burden, including ongoing symptoms often driven by inflammation. Corticosteroids are often the best medications to control disease activity, she said, but they can result in long-term toxicity.

 

What Makes DZP Unique?

Through CD40 ligand signaling, DZP has been shown to reduce B- and T-cell activation and to downregulate interferon pathways. Previous antibodies targeting the CD40 ligand have been associated with an increased risk for thromboembolic events. However, DZP lacks the Fc portion of the antibody, which can bind to platelets and cause clotting. Data from phase 1, 2, and 3 trials thus far do not show an elevated risk for these events, Clowse explained. In fact, safety signals were strong enough that patients with antiphospholipid antibodies — a key driver for blood clots in patients with SLE — were included in the trial.

In PHOENYCS GO, investigators enrolled 321 patients with moderate to severe SLE with persistently active or frequently flaring/relapsing-remitting disease activity despite stable standard of care (SOC) medications such as antimalarials, corticosteroids, and immunosuppressants.

Patients were randomized 2:1 to receive intravenous DZP (24 mg/kg) plus SOC or intravenous placebo plus SOC every 4 weeks, with patients and investigators blinded to treatment assignments.

Patients taking a corticosteroid dose > 7.5 mg/day began a mandatory steroid taper by week 8 of the trial, with the goal of reducing that to < 7.5 mg/day. The tapering regimen was at the discretion of providers and was adapted to each patient’s individual disease activity.

The primary endpoint was British Isles Lupus Assessment Group–based Composite Lupus Assessment (BICLA) response at week 48.

Patients in the DZP and placebo groups were on average 43.5 and 41.5 years old, respectively. More than 90% of patients were women, all on concomitant SLE medications. About half of the participants took a daily corticosteroid dose > 7.5 mg.

At 48 weeks, half of the DZP group (49.5%) achieved BICLA response compared with 34.6% in the placebo group (P = .0110). A higher proportion of patients taking DZP achieved SLE Responder Index-4 response than those taking placebo (60.1% vs 41.1%, respectively; P = .0014), and the rate of severe British Isles Lupus Assessment Group flares in the DZP group was half that of the placebo group (11.6% vs 23.4%; P = .0257). In the subgroup of patients who underwent corticosteroid tapering, 72.4% receiving DZP and 52.9% taking placebo reduced their dose to < 7.5 mg/day by 48 weeks (P = .0404).

DZP was generally well tolerated. Over 48 weeks, 82.6% of the DZP group and 75% of the placebo group reported treatment-emergent adverse events, but serious occurrences were more common in the placebo group (14.8%) than in the DZP group (9.9%). Herpes viral infections were higher in the placebo group, although there were three ophthalmic herpes cases in the DZP group. There was one case of acute myocardial infarction and one death linked to gangrene-related sepsis in patients receiving DZP.

 

A ‘Mild to Moderate’ Response

Although these are definitely positive results, they show a “mild to moderate response” to DZP, commented Gregory Gardner, MD, an emeritus professor in the Division of Rheumatology at the University of Washington, Seattle, and chair of the American College of Rheumatology’s annual meeting planning committee. He moderated the session where the research was presented. Although DZP showed efficacy among some patients, he noted, “there were still 51% patients that it didn’t work for.” 

The drug uses an alternative pathway to current lupus drugs, Gardner added, and more research is needed to understand how best to use this medication in practice.

Clowse noted that DZP could be particularly beneficial for patients with SLE who want to get pregnant. Many drugs used to treat the disease are teratogenic; however, “because of the lack of Fc portion on this drug, it very likely does not cross the placenta in any kind of significant amount,” she said. Although there are not yet any reproductive safety data on DZP, she added, “that is a great potential niche.”

Biogen and UCB, which are jointly developing DZP, aim to start a second phase 3 trial of DZP in patients with SLE, called PHOENYCS FLY, in 2024.

The trial was sponsored by UCB. Clowse is a consultant and has received grant/research support from GSK and UCB. Gardner 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 — 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 — 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.