TBD Meeting (3208-24)

WASHINGTON — Glucagon-like peptide 1 receptor agonist (GLP-1 RA) medications appear beneficial for people with systemic lupus erythematosus (SLE) and lupus nephritis, two new studies suggest. 

“The risk of cardiovascular disease is thought to be at least double that for people with lupus ... and we know the risk of progressing to end-stage renal disease [ESKD] for patients with lupus nephritis can be as high as 10%-30%, so there’s clearly a major unmet need for new treatments and approaches to improve these outcomes, perhaps with adjunctive treatment beyond our typical immunosuppressive therapy,” April Jorge, MD, of Massachusetts General Hospital, Boston, said at the annual meeting of the American College of Rheumatology (ACR). 

The GLP-1 RAs are approved for the treatment of type 2 diabetes (T2D) and obesity. They also have proven cardiovascular benefit, along with emerging data suggesting kidney protection independent of glucose lowering. Jorge presented findings from a study using data from the US multicenter electronic health record database TriNetX, showing that, among patients who had both T2D and SLE, those using GLP-1 RAs had lower risks for major adverse cardiac events (MACE), venous thrombosis, kidney disease progression, and all-cause mortality, compared with those using a different class of T2D medication. 

A second study using TriNetX, presented at the same ACR meeting session by Anna-Kay Palmer, MD, a third-year internal medicine resident at Jefferson Einstein Hospital, Philadelphia, Pennsylvania, showed that GLP-1 RAs reduced the risk of progression to ESKD in patients with lupus nephritis, possibly caused by reductions in pro-inflammatory mediators.

Asked to comment, session moderator Diane L. Kamen, MD, professor of medicine at the Medical University of South Carolina Division of Rheumatology, Charleston, said in an interview that she definitely supports the use of GLP-1 RAs for patients who have SLE and/or lupus nephritis and also a drug label indication, either T2D or obesity. “[The GLP-1 RA prescriber] will usually run it by rheumatology to make sure that it doesn’t conflict with any of their other medical treatment, and it’s very reassuring to know that they could actually get a win-win.” 

But as far as prescribing off-label for those with SLE/lupus nephritis who don’t have other GLP-1 RA indications, Kamen said, “that’s a black hole at this point. We need to do those prospective studies. But if they have another indication, yes.”

 

Cardiovascular, Kidney Benefits of GLP-1 RAs

Jorge noted that patients with lupus were excluded from the randomized clinical trials of GLP-1 RAs, so the current study was designed to investigate the potential impact of these medications on cardiovascular and kidney outcomes in patients with SLE and lupus nephritis. 

From TriNetX data for 46 healthcare organizations nationwide, a total of 96,511 patients with both SLE and T2D but not ESKD had initiated either a GLP-1 RA or another diabetes drug class, dipeptidyl peptidase 4 inhibitors (DPP4i), between October 2006 and August 2021. Of those, 29,177 had lupus nephritis. 

Propensity score matching for factors such as demographics, lupus severity, comorbidities, and medication use was used to emulate a randomized trial. This yielded 25,838 with SLE and T2D, of whom 910 initiated a GLP-1 RA and 1004 started a DPP4i, and 12,387 with lupus nephritis and T2D, including 267 on a GLP-1 RA and 324 on a DPP4i. After matching, the mean age was 55 years, more than 90% were women, and just under half were White individuals. About one third had chronic kidney disease stages ≥ 3, and about 15% had heart failure. 

Over an average follow-up time of 1.2-1.4 years among those with SLE, the hazard ratio (HR) for MACE (a composite of myocardial infarction, stroke, and heart failure) for those taking a GLP-1 RA vs a DPP4i was 0.66, a significant difference. And for venous thrombosis, the HR was also significant at 0.49.

Kidney disease progression, defined as an estimated glomerular filtration rate decline of 30% or more or new ESKD, was significantly less likely in the GLP-1 RA group, with a HR of 0.77. All-cause mortality also was dramatically reduced (HR, 0.26). As expected, there was no difference in control outcome, genital infections (HR, 1.02). 

In the subgroup with lupus nephritis, there were also lower risks for both MACE (HR, 0.64) and for renal progression (HR, 0.70). “The findings suggest similar cardiac and kidney benefits among patients with SLE and lupus nephritis as have been observed in other populations,” Jorge concluded. 

Kamen commented that the study design “was pretty brilliant, because you wouldn’t be able to do a placebo-controlled trial since the indication was diabetes ... but the fact is you do see that the GLP-1 RA gets the benefit whereas the other drug does not.”

Next steps, Jorge said, will be mechanistic studies to better understand the effects of GLP-1 RAs in lupus and other rheumatic diseases, prospective studies of GLP-1 RAs in SLE and lupus nephritis without diabetes, and clarification of ideal timing for GLP-1 RA use in SLE and lupus nephritis. 

“Ideally, with our prospective studies with these patients we can try to isolate the effect on patients with lupus and also better understand whether there might be an impact on disease activity through the anti-inflammatory effects of these medications, rather than just the cardioprotective and nephroprotective benefits,” she said. 

 

In Those With Lupus Nephritis, Kidney Protection Seen

In her presentation, Palmer noted that, despite immunosuppressive therapies for SLE, 10%-20% of patients who develop lupus nephritis will progress to ESKD within 5 years of diagnosis. 

She added that GLP-1 RAs have been shown to reduce albuminuria in people with diabetes and have been hypothesized to reduce inflammation through multiple pathways, thereby potentially reducing kidney disease independently of the presence of diabetes or weight loss. These pathways include modulating immune cell signaling and reducing pro-inflammatory cytokines. 

Based on all this, Palmer and colleagues used International Classification of Diseases – 10th edition diagnostic codes in TriNetX to identify 839 patients who had been diagnosed with lupus nephritis between 2014 and 2024 and who were prescribed liraglutide, dulaglutide, semaglutide, or exenatide for any time after the lupus nephritis diagnosis. Another 29,840 patients with lupus nephritis had not used GLP-1 RAs. 

After 1:1 propensity score matching for age, sex, race, ethnicity, presence of hypertension, diabetes, use of immunosuppressive and diabetes medication, smoking, obesity, and statin use, there were 735 individuals in each group. About two thirds in each had diabetes, whereas the rest had been prescribed the GLP-1 RAs for other indications. 

Patients who were not on GLP-1 RAs were twice as likely to develop ESKD or dialysis (8.88% vs 3.971%; odds ratio, 2.35; P = .001). 

Kamen pointed out that not including the use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers was a study flaw. On the other hand, the fact that not everyone in this study had diabetes was an advantage.

Jorge received grant/research support from Bristol-Myers Squibb, Cabaletta Bio, and the Lupus Clinical Investigator Network. Kamen is an adviser/review panel member for Alpine Immune Sciences. Palmer had no disclosures.

A version of this article appeared on Medscape.com.

WASHINGTON — Glucagon-like peptide 1 receptor agonist (GLP-1 RA) medications appear beneficial for people with systemic lupus erythematosus (SLE) and lupus nephritis, two new studies suggest. 

“The risk of cardiovascular disease is thought to be at least double that for people with lupus ... and we know the risk of progressing to end-stage renal disease [ESKD] for patients with lupus nephritis can be as high as 10%-30%, so there’s clearly a major unmet need for new treatments and approaches to improve these outcomes, perhaps with adjunctive treatment beyond our typical immunosuppressive therapy,” April Jorge, MD, of Massachusetts General Hospital, Boston, said at the annual meeting of the American College of Rheumatology (ACR). 

The GLP-1 RAs are approved for the treatment of type 2 diabetes (T2D) and obesity. They also have proven cardiovascular benefit, along with emerging data suggesting kidney protection independent of glucose lowering. Jorge presented findings from a study using data from the US multicenter electronic health record database TriNetX, showing that, among patients who had both T2D and SLE, those using GLP-1 RAs had lower risks for major adverse cardiac events (MACE), venous thrombosis, kidney disease progression, and all-cause mortality, compared with those using a different class of T2D medication. 

A second study using TriNetX, presented at the same ACR meeting session by Anna-Kay Palmer, MD, a third-year internal medicine resident at Jefferson Einstein Hospital, Philadelphia, Pennsylvania, showed that GLP-1 RAs reduced the risk of progression to ESKD in patients with lupus nephritis, possibly caused by reductions in pro-inflammatory mediators.

Asked to comment, session moderator Diane L. Kamen, MD, professor of medicine at the Medical University of South Carolina Division of Rheumatology, Charleston, said in an interview that she definitely supports the use of GLP-1 RAs for patients who have SLE and/or lupus nephritis and also a drug label indication, either T2D or obesity. “[The GLP-1 RA prescriber] will usually run it by rheumatology to make sure that it doesn’t conflict with any of their other medical treatment, and it’s very reassuring to know that they could actually get a win-win.” 

But as far as prescribing off-label for those with SLE/lupus nephritis who don’t have other GLP-1 RA indications, Kamen said, “that’s a black hole at this point. We need to do those prospective studies. But if they have another indication, yes.”

 

Cardiovascular, Kidney Benefits of GLP-1 RAs

Jorge noted that patients with lupus were excluded from the randomized clinical trials of GLP-1 RAs, so the current study was designed to investigate the potential impact of these medications on cardiovascular and kidney outcomes in patients with SLE and lupus nephritis. 

From TriNetX data for 46 healthcare organizations nationwide, a total of 96,511 patients with both SLE and T2D but not ESKD had initiated either a GLP-1 RA or another diabetes drug class, dipeptidyl peptidase 4 inhibitors (DPP4i), between October 2006 and August 2021. Of those, 29,177 had lupus nephritis. 

Propensity score matching for factors such as demographics, lupus severity, comorbidities, and medication use was used to emulate a randomized trial. This yielded 25,838 with SLE and T2D, of whom 910 initiated a GLP-1 RA and 1004 started a DPP4i, and 12,387 with lupus nephritis and T2D, including 267 on a GLP-1 RA and 324 on a DPP4i. After matching, the mean age was 55 years, more than 90% were women, and just under half were White individuals. About one third had chronic kidney disease stages ≥ 3, and about 15% had heart failure. 

Over an average follow-up time of 1.2-1.4 years among those with SLE, the hazard ratio (HR) for MACE (a composite of myocardial infarction, stroke, and heart failure) for those taking a GLP-1 RA vs a DPP4i was 0.66, a significant difference. And for venous thrombosis, the HR was also significant at 0.49.

Kidney disease progression, defined as an estimated glomerular filtration rate decline of 30% or more or new ESKD, was significantly less likely in the GLP-1 RA group, with a HR of 0.77. All-cause mortality also was dramatically reduced (HR, 0.26). As expected, there was no difference in control outcome, genital infections (HR, 1.02). 

In the subgroup with lupus nephritis, there were also lower risks for both MACE (HR, 0.64) and for renal progression (HR, 0.70). “The findings suggest similar cardiac and kidney benefits among patients with SLE and lupus nephritis as have been observed in other populations,” Jorge concluded. 

Kamen commented that the study design “was pretty brilliant, because you wouldn’t be able to do a placebo-controlled trial since the indication was diabetes ... but the fact is you do see that the GLP-1 RA gets the benefit whereas the other drug does not.”

Next steps, Jorge said, will be mechanistic studies to better understand the effects of GLP-1 RAs in lupus and other rheumatic diseases, prospective studies of GLP-1 RAs in SLE and lupus nephritis without diabetes, and clarification of ideal timing for GLP-1 RA use in SLE and lupus nephritis. 

“Ideally, with our prospective studies with these patients we can try to isolate the effect on patients with lupus and also better understand whether there might be an impact on disease activity through the anti-inflammatory effects of these medications, rather than just the cardioprotective and nephroprotective benefits,” she said. 

 

In Those With Lupus Nephritis, Kidney Protection Seen

In her presentation, Palmer noted that, despite immunosuppressive therapies for SLE, 10%-20% of patients who develop lupus nephritis will progress to ESKD within 5 years of diagnosis. 

She added that GLP-1 RAs have been shown to reduce albuminuria in people with diabetes and have been hypothesized to reduce inflammation through multiple pathways, thereby potentially reducing kidney disease independently of the presence of diabetes or weight loss. These pathways include modulating immune cell signaling and reducing pro-inflammatory cytokines. 

Based on all this, Palmer and colleagues used International Classification of Diseases – 10th edition diagnostic codes in TriNetX to identify 839 patients who had been diagnosed with lupus nephritis between 2014 and 2024 and who were prescribed liraglutide, dulaglutide, semaglutide, or exenatide for any time after the lupus nephritis diagnosis. Another 29,840 patients with lupus nephritis had not used GLP-1 RAs. 

After 1:1 propensity score matching for age, sex, race, ethnicity, presence of hypertension, diabetes, use of immunosuppressive and diabetes medication, smoking, obesity, and statin use, there were 735 individuals in each group. About two thirds in each had diabetes, whereas the rest had been prescribed the GLP-1 RAs for other indications. 

Patients who were not on GLP-1 RAs were twice as likely to develop ESKD or dialysis (8.88% vs 3.971%; odds ratio, 2.35; P = .001). 

Kamen pointed out that not including the use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers was a study flaw. On the other hand, the fact that not everyone in this study had diabetes was an advantage.

Jorge received grant/research support from Bristol-Myers Squibb, Cabaletta Bio, and the Lupus Clinical Investigator Network. Kamen is an adviser/review panel member for Alpine Immune Sciences. Palmer had no disclosures.

A version of this article appeared on Medscape.com.

WASHINGTON — Glucagon-like peptide 1 receptor agonist (GLP-1 RA) medications appear beneficial for people with systemic lupus erythematosus (SLE) and lupus nephritis, two new studies suggest. 

“The risk of cardiovascular disease is thought to be at least double that for people with lupus ... and we know the risk of progressing to end-stage renal disease [ESKD] for patients with lupus nephritis can be as high as 10%-30%, so there’s clearly a major unmet need for new treatments and approaches to improve these outcomes, perhaps with adjunctive treatment beyond our typical immunosuppressive therapy,” April Jorge, MD, of Massachusetts General Hospital, Boston, said at the annual meeting of the American College of Rheumatology (ACR). 

The GLP-1 RAs are approved for the treatment of type 2 diabetes (T2D) and obesity. They also have proven cardiovascular benefit, along with emerging data suggesting kidney protection independent of glucose lowering. Jorge presented findings from a study using data from the US multicenter electronic health record database TriNetX, showing that, among patients who had both T2D and SLE, those using GLP-1 RAs had lower risks for major adverse cardiac events (MACE), venous thrombosis, kidney disease progression, and all-cause mortality, compared with those using a different class of T2D medication. 

A second study using TriNetX, presented at the same ACR meeting session by Anna-Kay Palmer, MD, a third-year internal medicine resident at Jefferson Einstein Hospital, Philadelphia, Pennsylvania, showed that GLP-1 RAs reduced the risk of progression to ESKD in patients with lupus nephritis, possibly caused by reductions in pro-inflammatory mediators.

Asked to comment, session moderator Diane L. Kamen, MD, professor of medicine at the Medical University of South Carolina Division of Rheumatology, Charleston, said in an interview that she definitely supports the use of GLP-1 RAs for patients who have SLE and/or lupus nephritis and also a drug label indication, either T2D or obesity. “[The GLP-1 RA prescriber] will usually run it by rheumatology to make sure that it doesn’t conflict with any of their other medical treatment, and it’s very reassuring to know that they could actually get a win-win.” 

But as far as prescribing off-label for those with SLE/lupus nephritis who don’t have other GLP-1 RA indications, Kamen said, “that’s a black hole at this point. We need to do those prospective studies. But if they have another indication, yes.”

 

Cardiovascular, Kidney Benefits of GLP-1 RAs

Jorge noted that patients with lupus were excluded from the randomized clinical trials of GLP-1 RAs, so the current study was designed to investigate the potential impact of these medications on cardiovascular and kidney outcomes in patients with SLE and lupus nephritis. 

From TriNetX data for 46 healthcare organizations nationwide, a total of 96,511 patients with both SLE and T2D but not ESKD had initiated either a GLP-1 RA or another diabetes drug class, dipeptidyl peptidase 4 inhibitors (DPP4i), between October 2006 and August 2021. Of those, 29,177 had lupus nephritis. 

Propensity score matching for factors such as demographics, lupus severity, comorbidities, and medication use was used to emulate a randomized trial. This yielded 25,838 with SLE and T2D, of whom 910 initiated a GLP-1 RA and 1004 started a DPP4i, and 12,387 with lupus nephritis and T2D, including 267 on a GLP-1 RA and 324 on a DPP4i. After matching, the mean age was 55 years, more than 90% were women, and just under half were White individuals. About one third had chronic kidney disease stages ≥ 3, and about 15% had heart failure. 

Over an average follow-up time of 1.2-1.4 years among those with SLE, the hazard ratio (HR) for MACE (a composite of myocardial infarction, stroke, and heart failure) for those taking a GLP-1 RA vs a DPP4i was 0.66, a significant difference. And for venous thrombosis, the HR was also significant at 0.49.

Kidney disease progression, defined as an estimated glomerular filtration rate decline of 30% or more or new ESKD, was significantly less likely in the GLP-1 RA group, with a HR of 0.77. All-cause mortality also was dramatically reduced (HR, 0.26). As expected, there was no difference in control outcome, genital infections (HR, 1.02). 

In the subgroup with lupus nephritis, there were also lower risks for both MACE (HR, 0.64) and for renal progression (HR, 0.70). “The findings suggest similar cardiac and kidney benefits among patients with SLE and lupus nephritis as have been observed in other populations,” Jorge concluded. 

Kamen commented that the study design “was pretty brilliant, because you wouldn’t be able to do a placebo-controlled trial since the indication was diabetes ... but the fact is you do see that the GLP-1 RA gets the benefit whereas the other drug does not.”

Next steps, Jorge said, will be mechanistic studies to better understand the effects of GLP-1 RAs in lupus and other rheumatic diseases, prospective studies of GLP-1 RAs in SLE and lupus nephritis without diabetes, and clarification of ideal timing for GLP-1 RA use in SLE and lupus nephritis. 

“Ideally, with our prospective studies with these patients we can try to isolate the effect on patients with lupus and also better understand whether there might be an impact on disease activity through the anti-inflammatory effects of these medications, rather than just the cardioprotective and nephroprotective benefits,” she said. 

 

In Those With Lupus Nephritis, Kidney Protection Seen

In her presentation, Palmer noted that, despite immunosuppressive therapies for SLE, 10%-20% of patients who develop lupus nephritis will progress to ESKD within 5 years of diagnosis. 

She added that GLP-1 RAs have been shown to reduce albuminuria in people with diabetes and have been hypothesized to reduce inflammation through multiple pathways, thereby potentially reducing kidney disease independently of the presence of diabetes or weight loss. These pathways include modulating immune cell signaling and reducing pro-inflammatory cytokines. 

Based on all this, Palmer and colleagues used International Classification of Diseases – 10th edition diagnostic codes in TriNetX to identify 839 patients who had been diagnosed with lupus nephritis between 2014 and 2024 and who were prescribed liraglutide, dulaglutide, semaglutide, or exenatide for any time after the lupus nephritis diagnosis. Another 29,840 patients with lupus nephritis had not used GLP-1 RAs. 

After 1:1 propensity score matching for age, sex, race, ethnicity, presence of hypertension, diabetes, use of immunosuppressive and diabetes medication, smoking, obesity, and statin use, there were 735 individuals in each group. About two thirds in each had diabetes, whereas the rest had been prescribed the GLP-1 RAs for other indications. 

Patients who were not on GLP-1 RAs were twice as likely to develop ESKD or dialysis (8.88% vs 3.971%; odds ratio, 2.35; P = .001). 

Kamen pointed out that not including the use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers was a study flaw. On the other hand, the fact that not everyone in this study had diabetes was an advantage.

Jorge received grant/research support from Bristol-Myers Squibb, Cabaletta Bio, and the Lupus Clinical Investigator Network. Kamen is an adviser/review panel member for Alpine Immune Sciences. Palmer had no disclosures.

A version of this article appeared on Medscape.com.

WASHINGTON — A fully automated ultrasound scanning system combined with artificial intelligence–based disease activity scoring performed as well as expert rheumatologists in hand joint assessment of patients with rheumatoid arthritis (RA), new research found.

The system, made by a Danish company called ROPCA, comprises an ultrasound scanner called ARTHUR (RA Ultrasound Robot) that interacts directly with the patient and scans 11 joints per hand and a neural network–based software system, DIANA (Diagnosis Aid Network for RA), that evaluates the images and monitors RA activity.

 

The combined system classifies the degree of RA according to the joint European Alliance of Associations for Rheumatology (EULAR)–Outcome Measures in Rheumatology (OMERACT) standards for RA diagnosis. It received a CE Mark in Europe in 2022 and is currently in use in six rheumatology clinics in Denmark, Germany, Switzerland, and Austria, with more to come, ROPCA Co-founder and Chief Medical Officer Søren A. Just, MD, said in an interview.

“Automated systems could help rheumatologists in the early detection and monitoring of arthritis diseases. Systems can be placed or move in areas with insufficient rheumatological expertise,” Just said during a special late-breaker session presentation at the annual meeting of the American College of Rheumatology (ACR).

He said in an interview: “Currently, there are so many people referred and few and fewer rheumatologists. So we need to think differently. We need good automated assistants.” As a screening tool, the system can determine whether a person with hand pain has RA or just osteoarthritis “and also can give the patient an immediate answer, instead of waiting sometimes up to 6 months to get the information.”

Just, who is also a senior physician in the Department of Internal Medicine at Odense University Hospital in Denmark, said that his department is also using the system to assess flares in patients with established RA. “They can have a blood sample taken. They’re scanned by the robot, and you can see if there is any disease activity. But I think that screening of patients with joint pain is the beginning.”

Asked to comment, session moderator Gregory C. Gardner, MD, Emeritus Professor in the Division of Rheumatology at the University of Washington, Seattle, and a member of the ACR conference program committee, said in an interview “one of the reasons we chose to feature this abstract is because we’re interested in science at the convergence. We really thought this was a potential way to move the field forward for rheumatologists.”

Gardner said it’s an advantage that the patient could potentially have an ARTHUR scan with a DIANA report and get blood tests done prior to a visit with the rheumatologist. “It’s really time-consuming for a human to do these studies, so if you automate it, that’s a step forward in terms of having the data available for the rheumatologist to view and use sequentially to follow how patients are doing.”

When introducing Just’s presentation, Gardner called it “the coolest abstract of the meeting.”

 

Both DIANA and ARTHUR Performed At Least as Well as Human Rheumatologists

In the study, 30 patients with RA underwent two scans by ARTHUR, followed by a scan from a rheumatologist specialist in musculoskeletal ultrasound. The scans were sent to DIANA, who graded the images according to the Global OMERACT-EULAR Synovitis Score, as did the human rheumatologist.

A “ground truth” was established by another human expert who evaluated both ARTHUR’s and the other rheumatologist’s images, blinded to the scanning method. The image with the highest disease activity was deemed “ground truth,” and agreement with that was assessed for the two individual methods.

 

Just showed a video of a patient being scanned by ARTHUR. The machine verbally guided her through removing her jewelry, applying the gel, and placing her hand on the screen under the scanner. ARTHUR’s arm moved around on the patient’s hand, locating the best angles to take grayscale images and Doppler images and Doppler video. The scan takes 15-20 minutes, and the images are stored, Just said.

The study patients had a mean age of 65 years, and 23 of the 30 were men. Their average disease duration was 11 years, and mean Disease Activity Score in 28 joints using C-reactive protein was 3.86, indicating moderate disease. A majority (73%) of patients were taking disease-modifying antirheumatic drugs, and about one third were taking biologics. ARTHUR scanned a total of 660 joints, and 564 scans were successful.

For repeatability between the two ARTHUR scans, percent exact agreement was 63% for synovial hypertrophy, 75% for Doppler activity, and 60% combined. Percent close (within a point) agreements were 93%, 94%, and 92%, respectively. Binary agreements as to whether the joint was healthy vs diseased were 88%, 91%, and 85%, respectively.

At the joint level, ARTHUR and DIANA’s percent exact agreement with ground truth was 49% for synovial hypertrophy, 63% for Doppler activity, and 48% combined. Binary agreements with disease vs healthy were 80%, 88%, and 78%, respectively.

The human rheumatologists scored very similarly. Percent exact agreement with ground truth was 51% for synovial hypertrophy, 64% for Doppler activity, and 50% combined. Percent close agreements were 94%, 94%, and 92%, respectively. And binary agreements with diseased vs healthy were 83%, 91%, and 80%, respectively.

At the patient level (all joints combined), ARTHUR and DIANA’s binary disease assessment of healthy vs disease showed agreement with the ground truth of 87% for synovial hypertrophy, 83% for Doppler activity, and 87% combined. Here, the rheumatologists scored lower, at 53%, 67%, and 60%, respectively.

“In this study, we think the precision of ARTHUR and DIANA was comparable to that of an experienced rheumatologist, at both the joint and patient level,” Just said.

Gardner pointed out another advantage of the system. “DIANA doesn’t get fatigued. ... With human reading, the precision may change based on the time of day or stress level. ... But with DIANA, you’re going to get consistent information.”

Just said that the Arthritis Foundation in Germany recently put ARTHUR and DIANA on a bus and took it to cities that lacked a rheumatologist. Patients lined up, answered a questionnaire, had blood drawn, and received their scans. A rheumatologist on the bus then interpreted the data and consulted with the individuals about their RA risk. “In the last trip, we screened 800 patients in 6 days. So there are definitely possibilities here.”

Just is co-owner of ROPCA. Gardner had no disclosures.

A version of this article appeared on Medscape.com.

WASHINGTON — A fully automated ultrasound scanning system combined with artificial intelligence–based disease activity scoring performed as well as expert rheumatologists in hand joint assessment of patients with rheumatoid arthritis (RA), new research found.

The system, made by a Danish company called ROPCA, comprises an ultrasound scanner called ARTHUR (RA Ultrasound Robot) that interacts directly with the patient and scans 11 joints per hand and a neural network–based software system, DIANA (Diagnosis Aid Network for RA), that evaluates the images and monitors RA activity.

 

The combined system classifies the degree of RA according to the joint European Alliance of Associations for Rheumatology (EULAR)–Outcome Measures in Rheumatology (OMERACT) standards for RA diagnosis. It received a CE Mark in Europe in 2022 and is currently in use in six rheumatology clinics in Denmark, Germany, Switzerland, and Austria, with more to come, ROPCA Co-founder and Chief Medical Officer Søren A. Just, MD, said in an interview.

“Automated systems could help rheumatologists in the early detection and monitoring of arthritis diseases. Systems can be placed or move in areas with insufficient rheumatological expertise,” Just said during a special late-breaker session presentation at the annual meeting of the American College of Rheumatology (ACR).

He said in an interview: “Currently, there are so many people referred and few and fewer rheumatologists. So we need to think differently. We need good automated assistants.” As a screening tool, the system can determine whether a person with hand pain has RA or just osteoarthritis “and also can give the patient an immediate answer, instead of waiting sometimes up to 6 months to get the information.”

Just, who is also a senior physician in the Department of Internal Medicine at Odense University Hospital in Denmark, said that his department is also using the system to assess flares in patients with established RA. “They can have a blood sample taken. They’re scanned by the robot, and you can see if there is any disease activity. But I think that screening of patients with joint pain is the beginning.”

Asked to comment, session moderator Gregory C. Gardner, MD, Emeritus Professor in the Division of Rheumatology at the University of Washington, Seattle, and a member of the ACR conference program committee, said in an interview “one of the reasons we chose to feature this abstract is because we’re interested in science at the convergence. We really thought this was a potential way to move the field forward for rheumatologists.”

Gardner said it’s an advantage that the patient could potentially have an ARTHUR scan with a DIANA report and get blood tests done prior to a visit with the rheumatologist. “It’s really time-consuming for a human to do these studies, so if you automate it, that’s a step forward in terms of having the data available for the rheumatologist to view and use sequentially to follow how patients are doing.”

When introducing Just’s presentation, Gardner called it “the coolest abstract of the meeting.”

 

Both DIANA and ARTHUR Performed At Least as Well as Human Rheumatologists

In the study, 30 patients with RA underwent two scans by ARTHUR, followed by a scan from a rheumatologist specialist in musculoskeletal ultrasound. The scans were sent to DIANA, who graded the images according to the Global OMERACT-EULAR Synovitis Score, as did the human rheumatologist.

A “ground truth” was established by another human expert who evaluated both ARTHUR’s and the other rheumatologist’s images, blinded to the scanning method. The image with the highest disease activity was deemed “ground truth,” and agreement with that was assessed for the two individual methods.

 

Just showed a video of a patient being scanned by ARTHUR. The machine verbally guided her through removing her jewelry, applying the gel, and placing her hand on the screen under the scanner. ARTHUR’s arm moved around on the patient’s hand, locating the best angles to take grayscale images and Doppler images and Doppler video. The scan takes 15-20 minutes, and the images are stored, Just said.

The study patients had a mean age of 65 years, and 23 of the 30 were men. Their average disease duration was 11 years, and mean Disease Activity Score in 28 joints using C-reactive protein was 3.86, indicating moderate disease. A majority (73%) of patients were taking disease-modifying antirheumatic drugs, and about one third were taking biologics. ARTHUR scanned a total of 660 joints, and 564 scans were successful.

For repeatability between the two ARTHUR scans, percent exact agreement was 63% for synovial hypertrophy, 75% for Doppler activity, and 60% combined. Percent close (within a point) agreements were 93%, 94%, and 92%, respectively. Binary agreements as to whether the joint was healthy vs diseased were 88%, 91%, and 85%, respectively.

At the joint level, ARTHUR and DIANA’s percent exact agreement with ground truth was 49% for synovial hypertrophy, 63% for Doppler activity, and 48% combined. Binary agreements with disease vs healthy were 80%, 88%, and 78%, respectively.

The human rheumatologists scored very similarly. Percent exact agreement with ground truth was 51% for synovial hypertrophy, 64% for Doppler activity, and 50% combined. Percent close agreements were 94%, 94%, and 92%, respectively. And binary agreements with diseased vs healthy were 83%, 91%, and 80%, respectively.

At the patient level (all joints combined), ARTHUR and DIANA’s binary disease assessment of healthy vs disease showed agreement with the ground truth of 87% for synovial hypertrophy, 83% for Doppler activity, and 87% combined. Here, the rheumatologists scored lower, at 53%, 67%, and 60%, respectively.

“In this study, we think the precision of ARTHUR and DIANA was comparable to that of an experienced rheumatologist, at both the joint and patient level,” Just said.

Gardner pointed out another advantage of the system. “DIANA doesn’t get fatigued. ... With human reading, the precision may change based on the time of day or stress level. ... But with DIANA, you’re going to get consistent information.”

Just said that the Arthritis Foundation in Germany recently put ARTHUR and DIANA on a bus and took it to cities that lacked a rheumatologist. Patients lined up, answered a questionnaire, had blood drawn, and received their scans. A rheumatologist on the bus then interpreted the data and consulted with the individuals about their RA risk. “In the last trip, we screened 800 patients in 6 days. So there are definitely possibilities here.”

Just is co-owner of ROPCA. Gardner had no disclosures.

A version of this article appeared on Medscape.com.

WASHINGTON — A fully automated ultrasound scanning system combined with artificial intelligence–based disease activity scoring performed as well as expert rheumatologists in hand joint assessment of patients with rheumatoid arthritis (RA), new research found.

The system, made by a Danish company called ROPCA, comprises an ultrasound scanner called ARTHUR (RA Ultrasound Robot) that interacts directly with the patient and scans 11 joints per hand and a neural network–based software system, DIANA (Diagnosis Aid Network for RA), that evaluates the images and monitors RA activity.

 

The combined system classifies the degree of RA according to the joint European Alliance of Associations for Rheumatology (EULAR)–Outcome Measures in Rheumatology (OMERACT) standards for RA diagnosis. It received a CE Mark in Europe in 2022 and is currently in use in six rheumatology clinics in Denmark, Germany, Switzerland, and Austria, with more to come, ROPCA Co-founder and Chief Medical Officer Søren A. Just, MD, said in an interview.

“Automated systems could help rheumatologists in the early detection and monitoring of arthritis diseases. Systems can be placed or move in areas with insufficient rheumatological expertise,” Just said during a special late-breaker session presentation at the annual meeting of the American College of Rheumatology (ACR).

He said in an interview: “Currently, there are so many people referred and few and fewer rheumatologists. So we need to think differently. We need good automated assistants.” As a screening tool, the system can determine whether a person with hand pain has RA or just osteoarthritis “and also can give the patient an immediate answer, instead of waiting sometimes up to 6 months to get the information.”

Just, who is also a senior physician in the Department of Internal Medicine at Odense University Hospital in Denmark, said that his department is also using the system to assess flares in patients with established RA. “They can have a blood sample taken. They’re scanned by the robot, and you can see if there is any disease activity. But I think that screening of patients with joint pain is the beginning.”

Asked to comment, session moderator Gregory C. Gardner, MD, Emeritus Professor in the Division of Rheumatology at the University of Washington, Seattle, and a member of the ACR conference program committee, said in an interview “one of the reasons we chose to feature this abstract is because we’re interested in science at the convergence. We really thought this was a potential way to move the field forward for rheumatologists.”

Gardner said it’s an advantage that the patient could potentially have an ARTHUR scan with a DIANA report and get blood tests done prior to a visit with the rheumatologist. “It’s really time-consuming for a human to do these studies, so if you automate it, that’s a step forward in terms of having the data available for the rheumatologist to view and use sequentially to follow how patients are doing.”

When introducing Just’s presentation, Gardner called it “the coolest abstract of the meeting.”

 

Both DIANA and ARTHUR Performed At Least as Well as Human Rheumatologists

In the study, 30 patients with RA underwent two scans by ARTHUR, followed by a scan from a rheumatologist specialist in musculoskeletal ultrasound. The scans were sent to DIANA, who graded the images according to the Global OMERACT-EULAR Synovitis Score, as did the human rheumatologist.

A “ground truth” was established by another human expert who evaluated both ARTHUR’s and the other rheumatologist’s images, blinded to the scanning method. The image with the highest disease activity was deemed “ground truth,” and agreement with that was assessed for the two individual methods.

 

Just showed a video of a patient being scanned by ARTHUR. The machine verbally guided her through removing her jewelry, applying the gel, and placing her hand on the screen under the scanner. ARTHUR’s arm moved around on the patient’s hand, locating the best angles to take grayscale images and Doppler images and Doppler video. The scan takes 15-20 minutes, and the images are stored, Just said.

The study patients had a mean age of 65 years, and 23 of the 30 were men. Their average disease duration was 11 years, and mean Disease Activity Score in 28 joints using C-reactive protein was 3.86, indicating moderate disease. A majority (73%) of patients were taking disease-modifying antirheumatic drugs, and about one third were taking biologics. ARTHUR scanned a total of 660 joints, and 564 scans were successful.

For repeatability between the two ARTHUR scans, percent exact agreement was 63% for synovial hypertrophy, 75% for Doppler activity, and 60% combined. Percent close (within a point) agreements were 93%, 94%, and 92%, respectively. Binary agreements as to whether the joint was healthy vs diseased were 88%, 91%, and 85%, respectively.

At the joint level, ARTHUR and DIANA’s percent exact agreement with ground truth was 49% for synovial hypertrophy, 63% for Doppler activity, and 48% combined. Binary agreements with disease vs healthy were 80%, 88%, and 78%, respectively.

The human rheumatologists scored very similarly. Percent exact agreement with ground truth was 51% for synovial hypertrophy, 64% for Doppler activity, and 50% combined. Percent close agreements were 94%, 94%, and 92%, respectively. And binary agreements with diseased vs healthy were 83%, 91%, and 80%, respectively.

At the patient level (all joints combined), ARTHUR and DIANA’s binary disease assessment of healthy vs disease showed agreement with the ground truth of 87% for synovial hypertrophy, 83% for Doppler activity, and 87% combined. Here, the rheumatologists scored lower, at 53%, 67%, and 60%, respectively.

“In this study, we think the precision of ARTHUR and DIANA was comparable to that of an experienced rheumatologist, at both the joint and patient level,” Just said.

Gardner pointed out another advantage of the system. “DIANA doesn’t get fatigued. ... With human reading, the precision may change based on the time of day or stress level. ... But with DIANA, you’re going to get consistent information.”

Just said that the Arthritis Foundation in Germany recently put ARTHUR and DIANA on a bus and took it to cities that lacked a rheumatologist. Patients lined up, answered a questionnaire, had blood drawn, and received their scans. A rheumatologist on the bus then interpreted the data and consulted with the individuals about their RA risk. “In the last trip, we screened 800 patients in 6 days. So there are definitely possibilities here.”

Just is co-owner of ROPCA. Gardner had no 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 — 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 — 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 rheumatologists, 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 rheumatologists, 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 rheumatologists, 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.