Rheumatology

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.

A Mediterranean-inspired plant-based diet improved self-reported measures of gout as well as uric acid levels, a pilot study has found. 

There hasn’t been a lot of research on diet in gout, according to Anna Kretova, RD, who presented the study at the annual research symposium of the Gout Hyperuricemia and Crystal-Associated Disease Network. She noted that a 2019 systematic review of low-calorie diets, low-purine diets, and Mediterranean diets found that uric acid levels below 0.6 mmol/L were achieved only in those on the Mediterranean diet (Nutrients. 2019 Dec 4;11[12]:2955). A 2020 study compared a low-fat, high-carbohydrate, plant-based diet vs an animal-based, ketogenic diet in healthy individuals. After 2 weeks, uric acid levels increased in those on the animal-based, low-carb diet and decreased in those on the plant-based diet. 

Some foods are considered to be proinflammatory and generally come from animal origins, including saturated fats and animal protein in addition to ultraprocessed foods. Foods that have anti-inflammatory properties are mostly plant based and unprocessed and often rich in fiber. “From recent interventional studies, we also know that the whole-foods plant-based diet has shown to be effective as treatments of the main comorbidities of gout, such as obesity, cardiovascular disease, or [osteoarthritis],” said Kretova, who is a registered dietitian and a researcher at the Reade Rehabilitation and Rheumatology Center, Amsterdam, the Netherlands. 

Those findings led the researchers to develop a whole-foods, plant-based diet and test its effect on serum uric acid in patients with gout, as well as gout disease activity and cardiovascular disease risk. Participants could not eat meat, fish, eggs, or dairy. 

The trial included 33 individuals with gout who were randomized to a 16-week intervention with five consultations with a registered dietitian (n = 18) or a wait-list control group (n = 15) who received standard care. The mean age overall was 52 years, and 91% were men. The mean body mass index (BMI) was 32.6 kg/m2, and the median uric acid level was 0.50 mmol/L (8.4 mg/dL).

Among gout-related outcomes, the researchers noted improvements in gout severity as measured by visual analog scale (VAS; between group difference, –2.0; P =.01), pain as measured by VAS (between group difference, –2.0; P =.04), and uric acid levels after adjustment for age, sex, and BMI (between group difference, –0.05 mmol/L, P =.004). There were also improvements in the intervention group in weight loss (between group difference, –5.3 kg; P <.0001), BMI (between group difference, –1.7; P < .0001), waist circumference (between group difference, –3.9 cm; P = .004), and low-density lipoprotein (LDL) cholesterol (between group difference, –0.5; P = .007).

At 16 weeks, “we concluded that a Mediterranean-inspired whole-foods, plant-based diet significantly lowers serum uric acid in patients with gout and abdominal obesity, and additionally, the diet reduces gout-related pain and disease activity, promotes substantial weight loss, decreases weight circumference, and improves LDL cholesterol levels, and thus decreases [cardiovascular disease] risk in these patients,” Kretova said. 

She added that some might question whether a uric acid reduction of –0.05 mmol/L is clinically relevant. “We would argue it is because of the strong decrease in disease activity and pain in the intervention group,” Kretova said. 

The study is limited by its small size, the fact that it was not blinded, and the 4-month duration, which might be too short to capture potential indirect effects of diet on hyperuricemia and chronic inflammation, Kretova said. The group is planning to follow participants out to 12 months in an extension study.

During the Q&A session after the presentation, an audience member asked if the participants were vegetarians before they entered the study, and whether the dietary change could be sustained. “It’s a very good proof-of-concept study, but whether an intervention based entirely on plant-based therapy will be something that patients will be able to adhere to long term [is uncertain],” Kretova said.

She was optimistic, even though the participants generally enjoyed food and ate a lot of red meat. “I think there will be a gradation of people who can sustain and who cannot sustain [the diet]. From what we saw, people actually found it easier to follow than they expected, and a lot of participants changed their diet permanently for the better. Not everyone became [entirely] plant-based, but they became much more plant-based than they expected from themselves. So, it is definitely feasible,” she said.

Kretova reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

A Mediterranean-inspired plant-based diet improved self-reported measures of gout as well as uric acid levels, a pilot study has found. 

There hasn’t been a lot of research on diet in gout, according to Anna Kretova, RD, who presented the study at the annual research symposium of the Gout Hyperuricemia and Crystal-Associated Disease Network. She noted that a 2019 systematic review of low-calorie diets, low-purine diets, and Mediterranean diets found that uric acid levels below 0.6 mmol/L were achieved only in those on the Mediterranean diet (Nutrients. 2019 Dec 4;11[12]:2955). A 2020 study compared a low-fat, high-carbohydrate, plant-based diet vs an animal-based, ketogenic diet in healthy individuals. After 2 weeks, uric acid levels increased in those on the animal-based, low-carb diet and decreased in those on the plant-based diet. 

Some foods are considered to be proinflammatory and generally come from animal origins, including saturated fats and animal protein in addition to ultraprocessed foods. Foods that have anti-inflammatory properties are mostly plant based and unprocessed and often rich in fiber. “From recent interventional studies, we also know that the whole-foods plant-based diet has shown to be effective as treatments of the main comorbidities of gout, such as obesity, cardiovascular disease, or [osteoarthritis],” said Kretova, who is a registered dietitian and a researcher at the Reade Rehabilitation and Rheumatology Center, Amsterdam, the Netherlands. 

Those findings led the researchers to develop a whole-foods, plant-based diet and test its effect on serum uric acid in patients with gout, as well as gout disease activity and cardiovascular disease risk. Participants could not eat meat, fish, eggs, or dairy. 

The trial included 33 individuals with gout who were randomized to a 16-week intervention with five consultations with a registered dietitian (n = 18) or a wait-list control group (n = 15) who received standard care. The mean age overall was 52 years, and 91% were men. The mean body mass index (BMI) was 32.6 kg/m2, and the median uric acid level was 0.50 mmol/L (8.4 mg/dL).

Among gout-related outcomes, the researchers noted improvements in gout severity as measured by visual analog scale (VAS; between group difference, –2.0; P =.01), pain as measured by VAS (between group difference, –2.0; P =.04), and uric acid levels after adjustment for age, sex, and BMI (between group difference, –0.05 mmol/L, P =.004). There were also improvements in the intervention group in weight loss (between group difference, –5.3 kg; P <.0001), BMI (between group difference, –1.7; P < .0001), waist circumference (between group difference, –3.9 cm; P = .004), and low-density lipoprotein (LDL) cholesterol (between group difference, –0.5; P = .007).

At 16 weeks, “we concluded that a Mediterranean-inspired whole-foods, plant-based diet significantly lowers serum uric acid in patients with gout and abdominal obesity, and additionally, the diet reduces gout-related pain and disease activity, promotes substantial weight loss, decreases weight circumference, and improves LDL cholesterol levels, and thus decreases [cardiovascular disease] risk in these patients,” Kretova said. 

She added that some might question whether a uric acid reduction of –0.05 mmol/L is clinically relevant. “We would argue it is because of the strong decrease in disease activity and pain in the intervention group,” Kretova said. 

The study is limited by its small size, the fact that it was not blinded, and the 4-month duration, which might be too short to capture potential indirect effects of diet on hyperuricemia and chronic inflammation, Kretova said. The group is planning to follow participants out to 12 months in an extension study.

During the Q&A session after the presentation, an audience member asked if the participants were vegetarians before they entered the study, and whether the dietary change could be sustained. “It’s a very good proof-of-concept study, but whether an intervention based entirely on plant-based therapy will be something that patients will be able to adhere to long term [is uncertain],” Kretova said.

She was optimistic, even though the participants generally enjoyed food and ate a lot of red meat. “I think there will be a gradation of people who can sustain and who cannot sustain [the diet]. From what we saw, people actually found it easier to follow than they expected, and a lot of participants changed their diet permanently for the better. Not everyone became [entirely] plant-based, but they became much more plant-based than they expected from themselves. So, it is definitely feasible,” she said.

Kretova reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

A Mediterranean-inspired plant-based diet improved self-reported measures of gout as well as uric acid levels, a pilot study has found. 

There hasn’t been a lot of research on diet in gout, according to Anna Kretova, RD, who presented the study at the annual research symposium of the Gout Hyperuricemia and Crystal-Associated Disease Network. She noted that a 2019 systematic review of low-calorie diets, low-purine diets, and Mediterranean diets found that uric acid levels below 0.6 mmol/L were achieved only in those on the Mediterranean diet (Nutrients. 2019 Dec 4;11[12]:2955). A 2020 study compared a low-fat, high-carbohydrate, plant-based diet vs an animal-based, ketogenic diet in healthy individuals. After 2 weeks, uric acid levels increased in those on the animal-based, low-carb diet and decreased in those on the plant-based diet. 

Some foods are considered to be proinflammatory and generally come from animal origins, including saturated fats and animal protein in addition to ultraprocessed foods. Foods that have anti-inflammatory properties are mostly plant based and unprocessed and often rich in fiber. “From recent interventional studies, we also know that the whole-foods plant-based diet has shown to be effective as treatments of the main comorbidities of gout, such as obesity, cardiovascular disease, or [osteoarthritis],” said Kretova, who is a registered dietitian and a researcher at the Reade Rehabilitation and Rheumatology Center, Amsterdam, the Netherlands. 

Those findings led the researchers to develop a whole-foods, plant-based diet and test its effect on serum uric acid in patients with gout, as well as gout disease activity and cardiovascular disease risk. Participants could not eat meat, fish, eggs, or dairy. 

The trial included 33 individuals with gout who were randomized to a 16-week intervention with five consultations with a registered dietitian (n = 18) or a wait-list control group (n = 15) who received standard care. The mean age overall was 52 years, and 91% were men. The mean body mass index (BMI) was 32.6 kg/m2, and the median uric acid level was 0.50 mmol/L (8.4 mg/dL).

Among gout-related outcomes, the researchers noted improvements in gout severity as measured by visual analog scale (VAS; between group difference, –2.0; P =.01), pain as measured by VAS (between group difference, –2.0; P =.04), and uric acid levels after adjustment for age, sex, and BMI (between group difference, –0.05 mmol/L, P =.004). There were also improvements in the intervention group in weight loss (between group difference, –5.3 kg; P <.0001), BMI (between group difference, –1.7; P < .0001), waist circumference (between group difference, –3.9 cm; P = .004), and low-density lipoprotein (LDL) cholesterol (between group difference, –0.5; P = .007).

At 16 weeks, “we concluded that a Mediterranean-inspired whole-foods, plant-based diet significantly lowers serum uric acid in patients with gout and abdominal obesity, and additionally, the diet reduces gout-related pain and disease activity, promotes substantial weight loss, decreases weight circumference, and improves LDL cholesterol levels, and thus decreases [cardiovascular disease] risk in these patients,” Kretova said. 

She added that some might question whether a uric acid reduction of –0.05 mmol/L is clinically relevant. “We would argue it is because of the strong decrease in disease activity and pain in the intervention group,” Kretova said. 

The study is limited by its small size, the fact that it was not blinded, and the 4-month duration, which might be too short to capture potential indirect effects of diet on hyperuricemia and chronic inflammation, Kretova said. The group is planning to follow participants out to 12 months in an extension study.

During the Q&A session after the presentation, an audience member asked if the participants were vegetarians before they entered the study, and whether the dietary change could be sustained. “It’s a very good proof-of-concept study, but whether an intervention based entirely on plant-based therapy will be something that patients will be able to adhere to long term [is uncertain],” Kretova said.

She was optimistic, even though the participants generally enjoyed food and ate a lot of red meat. “I think there will be a gradation of people who can sustain and who cannot sustain [the diet]. From what we saw, people actually found it easier to follow than they expected, and a lot of participants changed their diet permanently for the better. Not everyone became [entirely] plant-based, but they became much more plant-based than they expected from themselves. So, it is definitely feasible,” she said.

Kretova reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

In a nearly unanimous vote at the annual research symposium of the Gout Hyperuricemia and Crystal-Associated Disease Network (G-CAN), members approved a revision to gout remission criteria first established in 2016. The new version simplifies the definition in response to patient comments that the earlier version was redundant in some areas. 

The previous version was developed following deliberations by 49 clinicians and researchers with experience in gout. They settled on a definition of gout remission that included five criteria:

• Serum urate levels lower than 0.36 mmol/L measured at least twice over 12 months, with no intervening values of 0.36 mmol/L or higher
• No gout flares over 12 months
• No tophi
• Pain score due to gout < 2 at least twice over 12 months on a 10-point Likert scale or 10-cm visual analog scale, with no intervening values ≥ 2
• Patient global assessment of gout disease activity < 2 on a 10-point Likert scale or 10-cm visual analog scale, with no intervening values of ≥ 2.

Some participants reported that patients sometimes misattributed pain from other sources while using patient-reported outcomes (PROs). The argument for keeping PROs was that they are validated measures and endorsed by Outcome Measures in Rheumatology. Nevertheless, there was no direct patient involvement in the development of the 2016 criteria.

Researchers later interviewed 20 individuals with well-controlled gout to get their feedback on the 2016 criteria. Those individuals endorsed the existing criteria and did not suggest any new ones, but they suggested that the pain due to gout and the absence of gout flares were redundant measures. One said: “If you have no flare-ups, you’ve got no pain; it sort of answers itself.”

“That was a bit challenging for us because it wasn’t quite what we expected, but I think it did make us look again at the definition and think about whether we could simplify the definition further,” Nicola Dalbeth, MBChB, said during a presentation at G-CAN. Dalbeth is an academic rheumatologist at the University of Auckland, in New Zealand, who was also the lead author of the original criteria.

 

Simplified Version Created With Only Three Criteria

In response to these points, researchers produced a revised version with only three criteria, including the serum urate, absence of gout flares, and absence of subcutaneous tophi at the time of assessment.

To determine if the simplified criteria performed well, they compared the original and revised remission criteria in the context of the CARES trial, the Nottingham nurse-led trial, and randomized controlled trials in patients with gout that were conducted in New Zealand (here and here).

Dansoa Tabi-Amponsah, a PhD candidate at the University of Auckland, presented results of a study comparing the two versions in the Nottingham trial, which included 517 participants who received nurse-led or usual general practitioner care. The nurse-led care included education, regular follow-up and serum urate testing, individualized advice on gout flare management, and escalation of urate-lowering therapy with a treat-to-target strategy.

Both definitions demonstrated a link between the nurse-led strategy and increased rates of remission at year 1 and year 2, although the simplified definition found that more patients were in remission (17.6% vs 9.9% at year 1 and 42.7% vs 28.4% at year 2, both P < .001). “This is something we’ve seen across all of our analyses,” said Tabi-Amponsah. 

Both criteria also found significant differences in remission rates between the nurse-led group in year 2 vs year 1 but not in the usual care group.

Participants who achieved remission had better gout impact scale scores in areas like worrying that a gout attack will occur, fears of worsening gout, and concerns about the impact of gout on future activities. “This is important because during that qualitative study, a key aspect of being in remission was no longer being worried about their gout, no longer feeling anxious about having constant gout flares, and having control over their gout. So, it’s important to note that despite the absence of PROs in that simplified definition, it’s still able to align with the patients’ perspectives of their disease state,” said Tabi-Amponsah.

During the Q&A period after her talk, an audience member asked whether the higher rate of remission found by the simplified criteria is actually a good thing. “If I compare that to rheumatoid arthritis, when you use DAS28 you have a lot more remission, but still progression. So, are we missing some people? Are we including people in remission that still have disease?” she asked. 

Tabi-Amponsah responded that the pain and patient global assessment domains seem to be quite difficult to achieve. In a separate analysis, the researchers examined tender and swollen joint counts and found that those achieving remission no longer had tender or swollen joints. “So, we don’t think the simplified definition is heavily misclassifying anyone as being in remission,” she said. 

During the Q&A following Dalbeth’s talk, an audience member asked about patients with what he described as “mountains of tophi,” despite responding well to uricase therapy. “They may take months or even a year to really resolve that burden. They may be doing very well, yet they’re not going to be in remission because they’ve still got visible tophi. So, are we underselling them, and do we need a different definition for them doing well that this doesn’t capture?” he asked.

Dalbeth suggested that patients with large amounts of tophi aren’t really in remission. “I think we do need to be thinking about the disease, not just in terms of just crystals or just inflammation, but actually trying to integrate both of those, and I think this is where these composite measures might work quite well. I think we need to be aiming for holistic disease control, which is essentially what this is,” she said. 

Tabi-Amponsah and Dalbeth did not disclose any financial relationships. 

 

A version of this article appeared on Medscape.com.

In a nearly unanimous vote at the annual research symposium of the Gout Hyperuricemia and Crystal-Associated Disease Network (G-CAN), members approved a revision to gout remission criteria first established in 2016. The new version simplifies the definition in response to patient comments that the earlier version was redundant in some areas. 

The previous version was developed following deliberations by 49 clinicians and researchers with experience in gout. They settled on a definition of gout remission that included five criteria:

• Serum urate levels lower than 0.36 mmol/L measured at least twice over 12 months, with no intervening values of 0.36 mmol/L or higher
• No gout flares over 12 months
• No tophi
• Pain score due to gout < 2 at least twice over 12 months on a 10-point Likert scale or 10-cm visual analog scale, with no intervening values ≥ 2
• Patient global assessment of gout disease activity < 2 on a 10-point Likert scale or 10-cm visual analog scale, with no intervening values of ≥ 2.

Some participants reported that patients sometimes misattributed pain from other sources while using patient-reported outcomes (PROs). The argument for keeping PROs was that they are validated measures and endorsed by Outcome Measures in Rheumatology. Nevertheless, there was no direct patient involvement in the development of the 2016 criteria.

Researchers later interviewed 20 individuals with well-controlled gout to get their feedback on the 2016 criteria. Those individuals endorsed the existing criteria and did not suggest any new ones, but they suggested that the pain due to gout and the absence of gout flares were redundant measures. One said: “If you have no flare-ups, you’ve got no pain; it sort of answers itself.”

“That was a bit challenging for us because it wasn’t quite what we expected, but I think it did make us look again at the definition and think about whether we could simplify the definition further,” Nicola Dalbeth, MBChB, said during a presentation at G-CAN. Dalbeth is an academic rheumatologist at the University of Auckland, in New Zealand, who was also the lead author of the original criteria.

 

Simplified Version Created With Only Three Criteria

In response to these points, researchers produced a revised version with only three criteria, including the serum urate, absence of gout flares, and absence of subcutaneous tophi at the time of assessment.

To determine if the simplified criteria performed well, they compared the original and revised remission criteria in the context of the CARES trial, the Nottingham nurse-led trial, and randomized controlled trials in patients with gout that were conducted in New Zealand (here and here).

Dansoa Tabi-Amponsah, a PhD candidate at the University of Auckland, presented results of a study comparing the two versions in the Nottingham trial, which included 517 participants who received nurse-led or usual general practitioner care. The nurse-led care included education, regular follow-up and serum urate testing, individualized advice on gout flare management, and escalation of urate-lowering therapy with a treat-to-target strategy.

Both definitions demonstrated a link between the nurse-led strategy and increased rates of remission at year 1 and year 2, although the simplified definition found that more patients were in remission (17.6% vs 9.9% at year 1 and 42.7% vs 28.4% at year 2, both P < .001). “This is something we’ve seen across all of our analyses,” said Tabi-Amponsah. 

Both criteria also found significant differences in remission rates between the nurse-led group in year 2 vs year 1 but not in the usual care group.

Participants who achieved remission had better gout impact scale scores in areas like worrying that a gout attack will occur, fears of worsening gout, and concerns about the impact of gout on future activities. “This is important because during that qualitative study, a key aspect of being in remission was no longer being worried about their gout, no longer feeling anxious about having constant gout flares, and having control over their gout. So, it’s important to note that despite the absence of PROs in that simplified definition, it’s still able to align with the patients’ perspectives of their disease state,” said Tabi-Amponsah.

During the Q&A period after her talk, an audience member asked whether the higher rate of remission found by the simplified criteria is actually a good thing. “If I compare that to rheumatoid arthritis, when you use DAS28 you have a lot more remission, but still progression. So, are we missing some people? Are we including people in remission that still have disease?” she asked. 

Tabi-Amponsah responded that the pain and patient global assessment domains seem to be quite difficult to achieve. In a separate analysis, the researchers examined tender and swollen joint counts and found that those achieving remission no longer had tender or swollen joints. “So, we don’t think the simplified definition is heavily misclassifying anyone as being in remission,” she said. 

During the Q&A following Dalbeth’s talk, an audience member asked about patients with what he described as “mountains of tophi,” despite responding well to uricase therapy. “They may take months or even a year to really resolve that burden. They may be doing very well, yet they’re not going to be in remission because they’ve still got visible tophi. So, are we underselling them, and do we need a different definition for them doing well that this doesn’t capture?” he asked.

Dalbeth suggested that patients with large amounts of tophi aren’t really in remission. “I think we do need to be thinking about the disease, not just in terms of just crystals or just inflammation, but actually trying to integrate both of those, and I think this is where these composite measures might work quite well. I think we need to be aiming for holistic disease control, which is essentially what this is,” she said. 

Tabi-Amponsah and Dalbeth did not disclose any financial relationships. 

 

A version of this article appeared on Medscape.com.

In a nearly unanimous vote at the annual research symposium of the Gout Hyperuricemia and Crystal-Associated Disease Network (G-CAN), members approved a revision to gout remission criteria first established in 2016. The new version simplifies the definition in response to patient comments that the earlier version was redundant in some areas. 

The previous version was developed following deliberations by 49 clinicians and researchers with experience in gout. They settled on a definition of gout remission that included five criteria:

• Serum urate levels lower than 0.36 mmol/L measured at least twice over 12 months, with no intervening values of 0.36 mmol/L or higher
• No gout flares over 12 months
• No tophi
• Pain score due to gout < 2 at least twice over 12 months on a 10-point Likert scale or 10-cm visual analog scale, with no intervening values ≥ 2
• Patient global assessment of gout disease activity < 2 on a 10-point Likert scale or 10-cm visual analog scale, with no intervening values of ≥ 2.

Some participants reported that patients sometimes misattributed pain from other sources while using patient-reported outcomes (PROs). The argument for keeping PROs was that they are validated measures and endorsed by Outcome Measures in Rheumatology. Nevertheless, there was no direct patient involvement in the development of the 2016 criteria.

Researchers later interviewed 20 individuals with well-controlled gout to get their feedback on the 2016 criteria. Those individuals endorsed the existing criteria and did not suggest any new ones, but they suggested that the pain due to gout and the absence of gout flares were redundant measures. One said: “If you have no flare-ups, you’ve got no pain; it sort of answers itself.”

“That was a bit challenging for us because it wasn’t quite what we expected, but I think it did make us look again at the definition and think about whether we could simplify the definition further,” Nicola Dalbeth, MBChB, said during a presentation at G-CAN. Dalbeth is an academic rheumatologist at the University of Auckland, in New Zealand, who was also the lead author of the original criteria.

 

Simplified Version Created With Only Three Criteria

In response to these points, researchers produced a revised version with only three criteria, including the serum urate, absence of gout flares, and absence of subcutaneous tophi at the time of assessment.

To determine if the simplified criteria performed well, they compared the original and revised remission criteria in the context of the CARES trial, the Nottingham nurse-led trial, and randomized controlled trials in patients with gout that were conducted in New Zealand (here and here).

Dansoa Tabi-Amponsah, a PhD candidate at the University of Auckland, presented results of a study comparing the two versions in the Nottingham trial, which included 517 participants who received nurse-led or usual general practitioner care. The nurse-led care included education, regular follow-up and serum urate testing, individualized advice on gout flare management, and escalation of urate-lowering therapy with a treat-to-target strategy.

Both definitions demonstrated a link between the nurse-led strategy and increased rates of remission at year 1 and year 2, although the simplified definition found that more patients were in remission (17.6% vs 9.9% at year 1 and 42.7% vs 28.4% at year 2, both P < .001). “This is something we’ve seen across all of our analyses,” said Tabi-Amponsah. 

Both criteria also found significant differences in remission rates between the nurse-led group in year 2 vs year 1 but not in the usual care group.

Participants who achieved remission had better gout impact scale scores in areas like worrying that a gout attack will occur, fears of worsening gout, and concerns about the impact of gout on future activities. “This is important because during that qualitative study, a key aspect of being in remission was no longer being worried about their gout, no longer feeling anxious about having constant gout flares, and having control over their gout. So, it’s important to note that despite the absence of PROs in that simplified definition, it’s still able to align with the patients’ perspectives of their disease state,” said Tabi-Amponsah.

During the Q&A period after her talk, an audience member asked whether the higher rate of remission found by the simplified criteria is actually a good thing. “If I compare that to rheumatoid arthritis, when you use DAS28 you have a lot more remission, but still progression. So, are we missing some people? Are we including people in remission that still have disease?” she asked. 

Tabi-Amponsah responded that the pain and patient global assessment domains seem to be quite difficult to achieve. In a separate analysis, the researchers examined tender and swollen joint counts and found that those achieving remission no longer had tender or swollen joints. “So, we don’t think the simplified definition is heavily misclassifying anyone as being in remission,” she said. 

During the Q&A following Dalbeth’s talk, an audience member asked about patients with what he described as “mountains of tophi,” despite responding well to uricase therapy. “They may take months or even a year to really resolve that burden. They may be doing very well, yet they’re not going to be in remission because they’ve still got visible tophi. So, are we underselling them, and do we need a different definition for them doing well that this doesn’t capture?” he asked.

Dalbeth suggested that patients with large amounts of tophi aren’t really in remission. “I think we do need to be thinking about the disease, not just in terms of just crystals or just inflammation, but actually trying to integrate both of those, and I think this is where these composite measures might work quite well. I think we need to be aiming for holistic disease control, which is essentially what this is,” she said. 

Tabi-Amponsah and Dalbeth did not disclose any financial relationships. 

 

A version of this article appeared on Medscape.com.

Efforts to combat hyperuricemia may find help from gut microbes, according to Dylan Dodd, MD, PhD, who spoke at the annual research symposium of the Gout, Hyperuricemia, and Crystal-Associated Disease Network.

Dodd is an assistant professor of pathology and microbiology and immunology at Stanford University, Palo Alto, California, where he studies novel metabolic pathways in microbes. “The idea is that we can leverage these novel pathways that microbes have as therapeutics to promote human health, and in particular for this meeting today, we’re focused on hyperuricemia and how microbes that break down purines may actually have a role as urate-lowering therapies,” Dodd said during his presentation.

Specifically, he highlighted the fact that some microbes found in the gut break down purines as a food source, producing both energy and molecular building blocks for their own use. Dietary purines, left intact, can otherwise be absorbed and metabolized by the body to produce urate.

Nucleic acids like DNA and RNA in the diet are first broken down by enzymes produced in the pancreas, resulting in purine nucleosides, which in turn are believed to be the source of purines absorbed in the small intestine and eventually into circulation, according to Dodd. “I really view urate in the intestine as being in equilibrium between being secreted into the lumen but also being reabsorbed, and specifically, as it pertains to microbes in the gut. If the microbes degrade the urate, then it will limit its reabsorption, and that could increase net excretion,” Dodd said.

There is evidence that some strains of Lactobacillus species, which are the most important group in the human gut, can metabolize purine nucleosides, he said. In recent years, researchers have screened for Lactobacillus species capable of metabolizing purine nucleosides. The research shows some strain-to-strain variation, but most are proprietary, making it impossible to conduct follow-up research. A small number of human trials have suggested efficacy, but they have generally been conducted in few patients with mixed results. “Overall, I think it’s promising that these lactobacilli probiotics could potentially be used as urate-lowering therapies,” Dodd said.

Aside from direct metabolism of purines, Dodd’s group has identified an additional pathway that some microbes can use to break down urate into short-chain fatty acids. His group cultured various purine nucleosides with various bacterial strains, including two Lactobacillus strains, under anaerobic conditions. The Lactobacillus strains did not degrade urate, but some bacterial species did. The group also found that Lactobacillus could convert nucleosides, including those derived from purines, into the smaller nucleobase compounds, but they did not consume the resultant purines. Some other types of bacteria consumed all purines “voraciously,” according to Dodd, and his team is working to identify the bacterial genetic pathways that drive the metabolic pathways. 

Such studies may open up various therapeutic pathways, he said. One is to employ Lactobacillus probiotics to convert purine nucleosides to their nucleobases, which could reduce absorption in the small intestine. Other bacteria could potentially be used to convert urate produced by paracellular reabsorption to short-chain fatty acids, which have potential benefits through their anti-inflammatory properties. Finally, probiotics could be engineered to degrade urate produced in the intestine. 

Dodd noted that probiotics would have the advantage of high patient acceptance and are generally regarded as safe. Some existing products might have purine-degrading capabilities but haven’t been tested, he said. However, there is strain-to-strain variation and the probiotic formulas would likely need to be optimized to reduce nucleobases. On the other hand, bacteria that degrade urate are likely safe since they have been found in the guts of healthy individuals. However, there are still potential safety concerns, and it is unknown if they could withstand the harsh conditions of the upper gastrointestinal tract or if they would remain active even in the presence of oxygen found in the small intestine, he said. 

During the Q&A period after his talk, Dodd was asked whether fructose consumption could suppress the function of anaerobic bacteria that naturally degrade purine. “When people talk about fructose-induced hyperuricemia, they talk about the ATP degradation in fructose metabolism in the liver or small intestine, [but] they never talk about this potential pathway in the gut,” the questioner said.

Dodd responded that his group found that some carbohydrates suppress urate degradation in some bacterial strains. “It’s certainly a possible mechanism that increased fructose intake could suppress microbial urate degradation in the gut, and that could contribute to hyperuricemia, but obviously more studies need to be done,” he said.

Another audience member wondered if antibiotic use could be tied to gout risk and whether serum urate levels might rise after antibiotic use. “Do you have any data on serum urate before and after antibiotic use, where you might expect to see changes which might support your hypothesis?” she asked. Dodd said that the group had done a retrospective analysis of data from Stanford’s medical records and did not find a change in serum urate after antibiotic exposure. However, a controlled feeding study of healthy individuals who later received antibiotics showed a large increase in urate levels, but the study did not include plasma samples. “It’s a really good question, and we hope to be able to follow that up,” he said.

Dodd disclosed no relevant financial relationships.

 

A version of this article appeared on Medscape.com.

Efforts to combat hyperuricemia may find help from gut microbes, according to Dylan Dodd, MD, PhD, who spoke at the annual research symposium of the Gout, Hyperuricemia, and Crystal-Associated Disease Network.

Dodd is an assistant professor of pathology and microbiology and immunology at Stanford University, Palo Alto, California, where he studies novel metabolic pathways in microbes. “The idea is that we can leverage these novel pathways that microbes have as therapeutics to promote human health, and in particular for this meeting today, we’re focused on hyperuricemia and how microbes that break down purines may actually have a role as urate-lowering therapies,” Dodd said during his presentation.

Specifically, he highlighted the fact that some microbes found in the gut break down purines as a food source, producing both energy and molecular building blocks for their own use. Dietary purines, left intact, can otherwise be absorbed and metabolized by the body to produce urate.

Nucleic acids like DNA and RNA in the diet are first broken down by enzymes produced in the pancreas, resulting in purine nucleosides, which in turn are believed to be the source of purines absorbed in the small intestine and eventually into circulation, according to Dodd. “I really view urate in the intestine as being in equilibrium between being secreted into the lumen but also being reabsorbed, and specifically, as it pertains to microbes in the gut. If the microbes degrade the urate, then it will limit its reabsorption, and that could increase net excretion,” Dodd said.

There is evidence that some strains of Lactobacillus species, which are the most important group in the human gut, can metabolize purine nucleosides, he said. In recent years, researchers have screened for Lactobacillus species capable of metabolizing purine nucleosides. The research shows some strain-to-strain variation, but most are proprietary, making it impossible to conduct follow-up research. A small number of human trials have suggested efficacy, but they have generally been conducted in few patients with mixed results. “Overall, I think it’s promising that these lactobacilli probiotics could potentially be used as urate-lowering therapies,” Dodd said.

Aside from direct metabolism of purines, Dodd’s group has identified an additional pathway that some microbes can use to break down urate into short-chain fatty acids. His group cultured various purine nucleosides with various bacterial strains, including two Lactobacillus strains, under anaerobic conditions. The Lactobacillus strains did not degrade urate, but some bacterial species did. The group also found that Lactobacillus could convert nucleosides, including those derived from purines, into the smaller nucleobase compounds, but they did not consume the resultant purines. Some other types of bacteria consumed all purines “voraciously,” according to Dodd, and his team is working to identify the bacterial genetic pathways that drive the metabolic pathways. 

Such studies may open up various therapeutic pathways, he said. One is to employ Lactobacillus probiotics to convert purine nucleosides to their nucleobases, which could reduce absorption in the small intestine. Other bacteria could potentially be used to convert urate produced by paracellular reabsorption to short-chain fatty acids, which have potential benefits through their anti-inflammatory properties. Finally, probiotics could be engineered to degrade urate produced in the intestine. 

Dodd noted that probiotics would have the advantage of high patient acceptance and are generally regarded as safe. Some existing products might have purine-degrading capabilities but haven’t been tested, he said. However, there is strain-to-strain variation and the probiotic formulas would likely need to be optimized to reduce nucleobases. On the other hand, bacteria that degrade urate are likely safe since they have been found in the guts of healthy individuals. However, there are still potential safety concerns, and it is unknown if they could withstand the harsh conditions of the upper gastrointestinal tract or if they would remain active even in the presence of oxygen found in the small intestine, he said. 

During the Q&A period after his talk, Dodd was asked whether fructose consumption could suppress the function of anaerobic bacteria that naturally degrade purine. “When people talk about fructose-induced hyperuricemia, they talk about the ATP degradation in fructose metabolism in the liver or small intestine, [but] they never talk about this potential pathway in the gut,” the questioner said.

Dodd responded that his group found that some carbohydrates suppress urate degradation in some bacterial strains. “It’s certainly a possible mechanism that increased fructose intake could suppress microbial urate degradation in the gut, and that could contribute to hyperuricemia, but obviously more studies need to be done,” he said.

Another audience member wondered if antibiotic use could be tied to gout risk and whether serum urate levels might rise after antibiotic use. “Do you have any data on serum urate before and after antibiotic use, where you might expect to see changes which might support your hypothesis?” she asked. Dodd said that the group had done a retrospective analysis of data from Stanford’s medical records and did not find a change in serum urate after antibiotic exposure. However, a controlled feeding study of healthy individuals who later received antibiotics showed a large increase in urate levels, but the study did not include plasma samples. “It’s a really good question, and we hope to be able to follow that up,” he said.

Dodd disclosed no relevant financial relationships.

 

A version of this article appeared on Medscape.com.

Efforts to combat hyperuricemia may find help from gut microbes, according to Dylan Dodd, MD, PhD, who spoke at the annual research symposium of the Gout, Hyperuricemia, and Crystal-Associated Disease Network.

Dodd is an assistant professor of pathology and microbiology and immunology at Stanford University, Palo Alto, California, where he studies novel metabolic pathways in microbes. “The idea is that we can leverage these novel pathways that microbes have as therapeutics to promote human health, and in particular for this meeting today, we’re focused on hyperuricemia and how microbes that break down purines may actually have a role as urate-lowering therapies,” Dodd said during his presentation.

Specifically, he highlighted the fact that some microbes found in the gut break down purines as a food source, producing both energy and molecular building blocks for their own use. Dietary purines, left intact, can otherwise be absorbed and metabolized by the body to produce urate.

Nucleic acids like DNA and RNA in the diet are first broken down by enzymes produced in the pancreas, resulting in purine nucleosides, which in turn are believed to be the source of purines absorbed in the small intestine and eventually into circulation, according to Dodd. “I really view urate in the intestine as being in equilibrium between being secreted into the lumen but also being reabsorbed, and specifically, as it pertains to microbes in the gut. If the microbes degrade the urate, then it will limit its reabsorption, and that could increase net excretion,” Dodd said.

There is evidence that some strains of Lactobacillus species, which are the most important group in the human gut, can metabolize purine nucleosides, he said. In recent years, researchers have screened for Lactobacillus species capable of metabolizing purine nucleosides. The research shows some strain-to-strain variation, but most are proprietary, making it impossible to conduct follow-up research. A small number of human trials have suggested efficacy, but they have generally been conducted in few patients with mixed results. “Overall, I think it’s promising that these lactobacilli probiotics could potentially be used as urate-lowering therapies,” Dodd said.

Aside from direct metabolism of purines, Dodd’s group has identified an additional pathway that some microbes can use to break down urate into short-chain fatty acids. His group cultured various purine nucleosides with various bacterial strains, including two Lactobacillus strains, under anaerobic conditions. The Lactobacillus strains did not degrade urate, but some bacterial species did. The group also found that Lactobacillus could convert nucleosides, including those derived from purines, into the smaller nucleobase compounds, but they did not consume the resultant purines. Some other types of bacteria consumed all purines “voraciously,” according to Dodd, and his team is working to identify the bacterial genetic pathways that drive the metabolic pathways. 

Such studies may open up various therapeutic pathways, he said. One is to employ Lactobacillus probiotics to convert purine nucleosides to their nucleobases, which could reduce absorption in the small intestine. Other bacteria could potentially be used to convert urate produced by paracellular reabsorption to short-chain fatty acids, which have potential benefits through their anti-inflammatory properties. Finally, probiotics could be engineered to degrade urate produced in the intestine. 

Dodd noted that probiotics would have the advantage of high patient acceptance and are generally regarded as safe. Some existing products might have purine-degrading capabilities but haven’t been tested, he said. However, there is strain-to-strain variation and the probiotic formulas would likely need to be optimized to reduce nucleobases. On the other hand, bacteria that degrade urate are likely safe since they have been found in the guts of healthy individuals. However, there are still potential safety concerns, and it is unknown if they could withstand the harsh conditions of the upper gastrointestinal tract or if they would remain active even in the presence of oxygen found in the small intestine, he said. 

During the Q&A period after his talk, Dodd was asked whether fructose consumption could suppress the function of anaerobic bacteria that naturally degrade purine. “When people talk about fructose-induced hyperuricemia, they talk about the ATP degradation in fructose metabolism in the liver or small intestine, [but] they never talk about this potential pathway in the gut,” the questioner said.

Dodd responded that his group found that some carbohydrates suppress urate degradation in some bacterial strains. “It’s certainly a possible mechanism that increased fructose intake could suppress microbial urate degradation in the gut, and that could contribute to hyperuricemia, but obviously more studies need to be done,” he said.

Another audience member wondered if antibiotic use could be tied to gout risk and whether serum urate levels might rise after antibiotic use. “Do you have any data on serum urate before and after antibiotic use, where you might expect to see changes which might support your hypothesis?” she asked. Dodd said that the group had done a retrospective analysis of data from Stanford’s medical records and did not find a change in serum urate after antibiotic exposure. However, a controlled feeding study of healthy individuals who later received antibiotics showed a large increase in urate levels, but the study did not include plasma samples. “It’s a really good question, and we hope to be able to follow that up,” he said.

Dodd disclosed no relevant financial relationships.

 

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.

Patients who discontinue treatment with the osteoporosis drug denosumab, despite transitioning to zoledronate, show significant losses in lumbar spine bone mineral density (BMD) within a year, according to the latest findings to show that the rapid rebound of bone loss after denosumab discontinuation is not easily prevented with other therapies — even bisphosphonates.

“When initiating denosumab for osteoporosis treatment, it is recommended to engage in thorough shared decision-making with the patient to ensure they understand the potential risks associated with discontinuing the medication,” senior author Shau-Huai Fu, MD, PhD, Department of Orthopedics, National Taiwan University Hospital Yunlin Branch, Douliu, told this news organization.

Furthermore, “integrating a case manager system is crucial to support long-term adherence and compliance,” he added.

The results are from the Denosumab Sequential Therapy prospective, open-label, parallel-group randomized clinical trial, published online in JAMA Network Open.

In the study, 101 patients were recruited between April 2019 and May 2021 at a referral center and two hospitals in Taiwan. The patients, including postmenopausal women and men over the age of 50, had been treated with regular denosumab for at least 2 years and had no previous exposure to other anti-osteoporosis medication.

They were randomized to treatment either with continuous denosumab at the standard dose of 60 mg twice yearly or to discontinue denosumab and receive the standard intravenous dose of the bisphosphonate zoledronate at 5 mg at the time when the next dose of denosumab would have been administered.

There were no differences between the two groups in serum bone turnover markers at baseline.

The current results, reflecting the first year of the 2-year study, show that, overall, those receiving zoledronate (n = 76), had a significant decrease in lumbar spine BMD, compared with a slight increase in the denosumab continuation group (–0.68% vs 1.30%, respectively; P = .03).

No significant differences were observed between the groups in terms of the study’s other measures of total hip BMD (median, 0% vs 1.12%; P = .24), and femoral neck BMD (median, 0.18% vs 0.17%; P = .71).

Additional findings from multivariable analyses in the study also supported results from previous studies showing that a longer duration of denosumab use is associated with a more substantial rebound effect: Among 15 of the denosumab users in the study who had ≥ 3 prior years of the drug, the reduction in lumbar spine BMD was even greater with zoledronate compared with denosumab continuation (–3.20% vs 1.30%; P = .003).

Though the lack of losses in the other measures of total hip and femoral neck BMD may seem encouraging, evidence from the bulk of other studies suggests cautious interpretation of those findings, Fu said.

“Although our study did not observe a noticeable decline in total hip or femoral neck BMD, other randomized controlled trials with longer durations of denosumab use have reported significant reductions in these areas,” Fu said. “Therefore, it cannot be assumed that non-lumbar spine regions are entirely safe.”

 

Fracture Risk Is the Overriding Concern

Meanwhile, the loss of lumbar spine BMD is of particular concern because of its role in what amounts to the broader, overriding concern of denosumab discontinuation — the risk for fracture, Fu noted.

“Real-world observations indicate that fractures caused by or associated with discontinuation of denosumab primarily occur in the spine,” he explained.

Previous research underscores the risk for fracture with denosumab discontinuation — and the greater risk with longer-term denosumab use, showing an 11.8% annual incidence of vertebral fracture after discontinuation of denosumab used for less than 2 years, increasing to 16.0% upon discontinuation after more than 2 years of treatment.

Randomized trials have shown sequential zoledronate to have some benefit in offsetting that risk, reducing first-year fracture risk by 3%-4% in some studies.

In the current study, 3 of 76 participants experienced a vertebral fracture in the first year of discontinuation, all involving women, including 2 who had been receiving denosumab for ≥ 4 years before medication transition.

If a transition to a bisphosphonate is anticipated, the collective findings suggest doing it as early on in denosumab treatment as possible, Fu and his colleagues noted in the study.

“When medication transition from denosumab is expected or when long-term denosumab treatment may not be suitable, earlier medication transition with potent sequential therapy should be considered,” they wrote.

 

Dosing Adjustments?

The findings add to the evidence that “patients who gain the most with denosumab are likely to lose the most with zoledronate,” Nelson Watts, MD, who authored an editorial accompanying the study, told this news organization.

Furthermore, “denosumab and other medications seem to do more [and faster] for BMD in the spine, so we expect more loss in the spine than in the hip,” said Watts, who is director of Mercy Health Osteoporosis and Bone Health Services, Bon Secours Mercy Health in Cincinnati, Ohio.

“Studies are needed but not yet done to see if a higher dose or more frequent zoledronate would be better for BMD than the ‘usual’ yearly dose,” Watts added.

The only published clinical recommendations on the matter are discussed in a position paper from the European Calcified Tissue Society (ECTS).

“Pending additional robust data, a pragmatic approach is to begin treatment with zoledronate 6 months after the last denosumab injection and monitor the effect with bone turnover markers, for example, 3 and 6 months after the zoledronate infusion,” they recommended.

In cases of increased bone turnover markers, including above the mean found in age- and sex-matched cohorts, “repeated infusion of zoledronate should be considered,” the society added.

If bone turnover markers are not available for monitoring the patients, “a pragmatic approach could be administrating a second infusion of zoledronate 6 months after the first infusion,” they wrote.

 

Clinicians Need to Be Proactive From the Start

Bente Langdahl, MD, of the Medical Department of Endocrinology, Aarhus University Hospital in Denmark, who was a coauthor on the ECTS position statement, told this news organization that clinicians should also be proactive on the other side of treatment — before it begins — to prevent problems with discontinuation.

“I think denosumab is a very good treatment for some patients with high fracture risk and very low BMD, but both patients and clinicians should know that this treatment is either lifelong or there needs to be a plan for discontinuation,” Langdahl said.

Langdahl noted that denosumab is coming off patent soon; hence, issues with cost could become more manageable.

But until then, “I think [cost] should be considered before starting treatment because if patients cannot afford denosumab, they should have been started on zoledronate from the beginning.”

 

Discontinuation Reasons Vary

Research indicates that, broadly, adherence to denosumab ranges from about 45% to 72% at 2 years, with some reasons for discontinuation including the need for dental treatment or cost, Fu and colleagues reported.

Fu added, however, that other reasons for discontinuing denosumab “are not due to ‘need’ but rather factors such as relocating, missing follow-up appointments, or poor adherence.”

Lorenz Hofbauer, MD, who is head of the Division of Endocrinology, Diabetes, and Bone Diseases, Department of Medicine III at the Technical University Medical Center in Dresden, Germany, noted that another issue contributing to some hesitation by patients about remaining on, or even initiating denosumab, is the known risk for osteonecrosis of the jaw (ONJ).

Though reported as being rare, research continuing to stir concern for ONJ with denosumab use includes one recent study of patients with breast cancer showing those treated with denosumab had a fivefold higher risk for ONJ vs those on bisphosphonates.

“About 20% of my patients have ONJ concerns or other questions, which may delay treatment with denosumab or other therapies,” Hofbauer told this news organization.

“There is a high need to discuss risk versus benefits toward a shared decision-making,” he said.

Conversely, however, Hofbauer noted that adherence to denosumab at his center is fairly high — at 90%, which he says is largely credited to an electronically supported recall system in place at the center.

Denosumab maker Amgen also offers patient reminders via email, text, or phone through its Bone Matters patient support system, which also provides access to a call center for questions or to update treatment appointment information.

In terms of the ongoing question of how to best prevent fracture risk when patients do wind up discontinuing denosumab, Watts concluded in his editorial that more robust studies are needed.

“The dilemma is what to do with longer-term users who stop, and the real question is not what happens to BMD, but what happens to fracture risk,” he wrote.

“It is unlikely that the fracture risk question can be answered due to ethical limitations, but finding the best option, [whether it is] oral or intravenous bisphosphonate, timing, dose, and frequency, to minimize bone loss and the rebound increase in bone resorption after stopping long-term denosumab requires larger and longer studies of better design.”

The authors had no disclosures to report. Watts has been an investigator, consultant, and speaker for Amgen outside of the published editorial. Hofbauer is on advisory boards for Alexion Pharmaceuticals, Amolyt Pharma, Amgen, and UCB. Langdahl has been a primary investigator on previous and ongoing clinical trials involving denosumab.

A version of this article appeared on Medscape.com.

Patients who discontinue treatment with the osteoporosis drug denosumab, despite transitioning to zoledronate, show significant losses in lumbar spine bone mineral density (BMD) within a year, according to the latest findings to show that the rapid rebound of bone loss after denosumab discontinuation is not easily prevented with other therapies — even bisphosphonates.

“When initiating denosumab for osteoporosis treatment, it is recommended to engage in thorough shared decision-making with the patient to ensure they understand the potential risks associated with discontinuing the medication,” senior author Shau-Huai Fu, MD, PhD, Department of Orthopedics, National Taiwan University Hospital Yunlin Branch, Douliu, told this news organization.

Furthermore, “integrating a case manager system is crucial to support long-term adherence and compliance,” he added.

The results are from the Denosumab Sequential Therapy prospective, open-label, parallel-group randomized clinical trial, published online in JAMA Network Open.

In the study, 101 patients were recruited between April 2019 and May 2021 at a referral center and two hospitals in Taiwan. The patients, including postmenopausal women and men over the age of 50, had been treated with regular denosumab for at least 2 years and had no previous exposure to other anti-osteoporosis medication.

They were randomized to treatment either with continuous denosumab at the standard dose of 60 mg twice yearly or to discontinue denosumab and receive the standard intravenous dose of the bisphosphonate zoledronate at 5 mg at the time when the next dose of denosumab would have been administered.

There were no differences between the two groups in serum bone turnover markers at baseline.

The current results, reflecting the first year of the 2-year study, show that, overall, those receiving zoledronate (n = 76), had a significant decrease in lumbar spine BMD, compared with a slight increase in the denosumab continuation group (–0.68% vs 1.30%, respectively; P = .03).

No significant differences were observed between the groups in terms of the study’s other measures of total hip BMD (median, 0% vs 1.12%; P = .24), and femoral neck BMD (median, 0.18% vs 0.17%; P = .71).

Additional findings from multivariable analyses in the study also supported results from previous studies showing that a longer duration of denosumab use is associated with a more substantial rebound effect: Among 15 of the denosumab users in the study who had ≥ 3 prior years of the drug, the reduction in lumbar spine BMD was even greater with zoledronate compared with denosumab continuation (–3.20% vs 1.30%; P = .003).

Though the lack of losses in the other measures of total hip and femoral neck BMD may seem encouraging, evidence from the bulk of other studies suggests cautious interpretation of those findings, Fu said.

“Although our study did not observe a noticeable decline in total hip or femoral neck BMD, other randomized controlled trials with longer durations of denosumab use have reported significant reductions in these areas,” Fu said. “Therefore, it cannot be assumed that non-lumbar spine regions are entirely safe.”

 

Fracture Risk Is the Overriding Concern

Meanwhile, the loss of lumbar spine BMD is of particular concern because of its role in what amounts to the broader, overriding concern of denosumab discontinuation — the risk for fracture, Fu noted.

“Real-world observations indicate that fractures caused by or associated with discontinuation of denosumab primarily occur in the spine,” he explained.

Previous research underscores the risk for fracture with denosumab discontinuation — and the greater risk with longer-term denosumab use, showing an 11.8% annual incidence of vertebral fracture after discontinuation of denosumab used for less than 2 years, increasing to 16.0% upon discontinuation after more than 2 years of treatment.

Randomized trials have shown sequential zoledronate to have some benefit in offsetting that risk, reducing first-year fracture risk by 3%-4% in some studies.

In the current study, 3 of 76 participants experienced a vertebral fracture in the first year of discontinuation, all involving women, including 2 who had been receiving denosumab for ≥ 4 years before medication transition.

If a transition to a bisphosphonate is anticipated, the collective findings suggest doing it as early on in denosumab treatment as possible, Fu and his colleagues noted in the study.

“When medication transition from denosumab is expected or when long-term denosumab treatment may not be suitable, earlier medication transition with potent sequential therapy should be considered,” they wrote.

 

Dosing Adjustments?

The findings add to the evidence that “patients who gain the most with denosumab are likely to lose the most with zoledronate,” Nelson Watts, MD, who authored an editorial accompanying the study, told this news organization.

Furthermore, “denosumab and other medications seem to do more [and faster] for BMD in the spine, so we expect more loss in the spine than in the hip,” said Watts, who is director of Mercy Health Osteoporosis and Bone Health Services, Bon Secours Mercy Health in Cincinnati, Ohio.

“Studies are needed but not yet done to see if a higher dose or more frequent zoledronate would be better for BMD than the ‘usual’ yearly dose,” Watts added.

The only published clinical recommendations on the matter are discussed in a position paper from the European Calcified Tissue Society (ECTS).

“Pending additional robust data, a pragmatic approach is to begin treatment with zoledronate 6 months after the last denosumab injection and monitor the effect with bone turnover markers, for example, 3 and 6 months after the zoledronate infusion,” they recommended.

In cases of increased bone turnover markers, including above the mean found in age- and sex-matched cohorts, “repeated infusion of zoledronate should be considered,” the society added.

If bone turnover markers are not available for monitoring the patients, “a pragmatic approach could be administrating a second infusion of zoledronate 6 months after the first infusion,” they wrote.

 

Clinicians Need to Be Proactive From the Start

Bente Langdahl, MD, of the Medical Department of Endocrinology, Aarhus University Hospital in Denmark, who was a coauthor on the ECTS position statement, told this news organization that clinicians should also be proactive on the other side of treatment — before it begins — to prevent problems with discontinuation.

“I think denosumab is a very good treatment for some patients with high fracture risk and very low BMD, but both patients and clinicians should know that this treatment is either lifelong or there needs to be a plan for discontinuation,” Langdahl said.

Langdahl noted that denosumab is coming off patent soon; hence, issues with cost could become more manageable.

But until then, “I think [cost] should be considered before starting treatment because if patients cannot afford denosumab, they should have been started on zoledronate from the beginning.”

 

Discontinuation Reasons Vary

Research indicates that, broadly, adherence to denosumab ranges from about 45% to 72% at 2 years, with some reasons for discontinuation including the need for dental treatment or cost, Fu and colleagues reported.

Fu added, however, that other reasons for discontinuing denosumab “are not due to ‘need’ but rather factors such as relocating, missing follow-up appointments, or poor adherence.”

Lorenz Hofbauer, MD, who is head of the Division of Endocrinology, Diabetes, and Bone Diseases, Department of Medicine III at the Technical University Medical Center in Dresden, Germany, noted that another issue contributing to some hesitation by patients about remaining on, or even initiating denosumab, is the known risk for osteonecrosis of the jaw (ONJ).

Though reported as being rare, research continuing to stir concern for ONJ with denosumab use includes one recent study of patients with breast cancer showing those treated with denosumab had a fivefold higher risk for ONJ vs those on bisphosphonates.

“About 20% of my patients have ONJ concerns or other questions, which may delay treatment with denosumab or other therapies,” Hofbauer told this news organization.

“There is a high need to discuss risk versus benefits toward a shared decision-making,” he said.

Conversely, however, Hofbauer noted that adherence to denosumab at his center is fairly high — at 90%, which he says is largely credited to an electronically supported recall system in place at the center.

Denosumab maker Amgen also offers patient reminders via email, text, or phone through its Bone Matters patient support system, which also provides access to a call center for questions or to update treatment appointment information.

In terms of the ongoing question of how to best prevent fracture risk when patients do wind up discontinuing denosumab, Watts concluded in his editorial that more robust studies are needed.

“The dilemma is what to do with longer-term users who stop, and the real question is not what happens to BMD, but what happens to fracture risk,” he wrote.

“It is unlikely that the fracture risk question can be answered due to ethical limitations, but finding the best option, [whether it is] oral or intravenous bisphosphonate, timing, dose, and frequency, to minimize bone loss and the rebound increase in bone resorption after stopping long-term denosumab requires larger and longer studies of better design.”

The authors had no disclosures to report. Watts has been an investigator, consultant, and speaker for Amgen outside of the published editorial. Hofbauer is on advisory boards for Alexion Pharmaceuticals, Amolyt Pharma, Amgen, and UCB. Langdahl has been a primary investigator on previous and ongoing clinical trials involving denosumab.

A version of this article appeared on Medscape.com.

Patients who discontinue treatment with the osteoporosis drug denosumab, despite transitioning to zoledronate, show significant losses in lumbar spine bone mineral density (BMD) within a year, according to the latest findings to show that the rapid rebound of bone loss after denosumab discontinuation is not easily prevented with other therapies — even bisphosphonates.

“When initiating denosumab for osteoporosis treatment, it is recommended to engage in thorough shared decision-making with the patient to ensure they understand the potential risks associated with discontinuing the medication,” senior author Shau-Huai Fu, MD, PhD, Department of Orthopedics, National Taiwan University Hospital Yunlin Branch, Douliu, told this news organization.

Furthermore, “integrating a case manager system is crucial to support long-term adherence and compliance,” he added.

The results are from the Denosumab Sequential Therapy prospective, open-label, parallel-group randomized clinical trial, published online in JAMA Network Open.

In the study, 101 patients were recruited between April 2019 and May 2021 at a referral center and two hospitals in Taiwan. The patients, including postmenopausal women and men over the age of 50, had been treated with regular denosumab for at least 2 years and had no previous exposure to other anti-osteoporosis medication.

They were randomized to treatment either with continuous denosumab at the standard dose of 60 mg twice yearly or to discontinue denosumab and receive the standard intravenous dose of the bisphosphonate zoledronate at 5 mg at the time when the next dose of denosumab would have been administered.

There were no differences between the two groups in serum bone turnover markers at baseline.

The current results, reflecting the first year of the 2-year study, show that, overall, those receiving zoledronate (n = 76), had a significant decrease in lumbar spine BMD, compared with a slight increase in the denosumab continuation group (–0.68% vs 1.30%, respectively; P = .03).

No significant differences were observed between the groups in terms of the study’s other measures of total hip BMD (median, 0% vs 1.12%; P = .24), and femoral neck BMD (median, 0.18% vs 0.17%; P = .71).

Additional findings from multivariable analyses in the study also supported results from previous studies showing that a longer duration of denosumab use is associated with a more substantial rebound effect: Among 15 of the denosumab users in the study who had ≥ 3 prior years of the drug, the reduction in lumbar spine BMD was even greater with zoledronate compared with denosumab continuation (–3.20% vs 1.30%; P = .003).

Though the lack of losses in the other measures of total hip and femoral neck BMD may seem encouraging, evidence from the bulk of other studies suggests cautious interpretation of those findings, Fu said.

“Although our study did not observe a noticeable decline in total hip or femoral neck BMD, other randomized controlled trials with longer durations of denosumab use have reported significant reductions in these areas,” Fu said. “Therefore, it cannot be assumed that non-lumbar spine regions are entirely safe.”

 

Fracture Risk Is the Overriding Concern

Meanwhile, the loss of lumbar spine BMD is of particular concern because of its role in what amounts to the broader, overriding concern of denosumab discontinuation — the risk for fracture, Fu noted.

“Real-world observations indicate that fractures caused by or associated with discontinuation of denosumab primarily occur in the spine,” he explained.

Previous research underscores the risk for fracture with denosumab discontinuation — and the greater risk with longer-term denosumab use, showing an 11.8% annual incidence of vertebral fracture after discontinuation of denosumab used for less than 2 years, increasing to 16.0% upon discontinuation after more than 2 years of treatment.

Randomized trials have shown sequential zoledronate to have some benefit in offsetting that risk, reducing first-year fracture risk by 3%-4% in some studies.

In the current study, 3 of 76 participants experienced a vertebral fracture in the first year of discontinuation, all involving women, including 2 who had been receiving denosumab for ≥ 4 years before medication transition.

If a transition to a bisphosphonate is anticipated, the collective findings suggest doing it as early on in denosumab treatment as possible, Fu and his colleagues noted in the study.

“When medication transition from denosumab is expected or when long-term denosumab treatment may not be suitable, earlier medication transition with potent sequential therapy should be considered,” they wrote.

 

Dosing Adjustments?

The findings add to the evidence that “patients who gain the most with denosumab are likely to lose the most with zoledronate,” Nelson Watts, MD, who authored an editorial accompanying the study, told this news organization.

Furthermore, “denosumab and other medications seem to do more [and faster] for BMD in the spine, so we expect more loss in the spine than in the hip,” said Watts, who is director of Mercy Health Osteoporosis and Bone Health Services, Bon Secours Mercy Health in Cincinnati, Ohio.

“Studies are needed but not yet done to see if a higher dose or more frequent zoledronate would be better for BMD than the ‘usual’ yearly dose,” Watts added.

The only published clinical recommendations on the matter are discussed in a position paper from the European Calcified Tissue Society (ECTS).

“Pending additional robust data, a pragmatic approach is to begin treatment with zoledronate 6 months after the last denosumab injection and monitor the effect with bone turnover markers, for example, 3 and 6 months after the zoledronate infusion,” they recommended.

In cases of increased bone turnover markers, including above the mean found in age- and sex-matched cohorts, “repeated infusion of zoledronate should be considered,” the society added.

If bone turnover markers are not available for monitoring the patients, “a pragmatic approach could be administrating a second infusion of zoledronate 6 months after the first infusion,” they wrote.

 

Clinicians Need to Be Proactive From the Start

Bente Langdahl, MD, of the Medical Department of Endocrinology, Aarhus University Hospital in Denmark, who was a coauthor on the ECTS position statement, told this news organization that clinicians should also be proactive on the other side of treatment — before it begins — to prevent problems with discontinuation.

“I think denosumab is a very good treatment for some patients with high fracture risk and very low BMD, but both patients and clinicians should know that this treatment is either lifelong or there needs to be a plan for discontinuation,” Langdahl said.

Langdahl noted that denosumab is coming off patent soon; hence, issues with cost could become more manageable.

But until then, “I think [cost] should be considered before starting treatment because if patients cannot afford denosumab, they should have been started on zoledronate from the beginning.”

 

Discontinuation Reasons Vary

Research indicates that, broadly, adherence to denosumab ranges from about 45% to 72% at 2 years, with some reasons for discontinuation including the need for dental treatment or cost, Fu and colleagues reported.

Fu added, however, that other reasons for discontinuing denosumab “are not due to ‘need’ but rather factors such as relocating, missing follow-up appointments, or poor adherence.”

Lorenz Hofbauer, MD, who is head of the Division of Endocrinology, Diabetes, and Bone Diseases, Department of Medicine III at the Technical University Medical Center in Dresden, Germany, noted that another issue contributing to some hesitation by patients about remaining on, or even initiating denosumab, is the known risk for osteonecrosis of the jaw (ONJ).

Though reported as being rare, research continuing to stir concern for ONJ with denosumab use includes one recent study of patients with breast cancer showing those treated with denosumab had a fivefold higher risk for ONJ vs those on bisphosphonates.

“About 20% of my patients have ONJ concerns or other questions, which may delay treatment with denosumab or other therapies,” Hofbauer told this news organization.

“There is a high need to discuss risk versus benefits toward a shared decision-making,” he said.

Conversely, however, Hofbauer noted that adherence to denosumab at his center is fairly high — at 90%, which he says is largely credited to an electronically supported recall system in place at the center.

Denosumab maker Amgen also offers patient reminders via email, text, or phone through its Bone Matters patient support system, which also provides access to a call center for questions or to update treatment appointment information.

In terms of the ongoing question of how to best prevent fracture risk when patients do wind up discontinuing denosumab, Watts concluded in his editorial that more robust studies are needed.

“The dilemma is what to do with longer-term users who stop, and the real question is not what happens to BMD, but what happens to fracture risk,” he wrote.

“It is unlikely that the fracture risk question can be answered due to ethical limitations, but finding the best option, [whether it is] oral or intravenous bisphosphonate, timing, dose, and frequency, to minimize bone loss and the rebound increase in bone resorption after stopping long-term denosumab requires larger and longer studies of better design.”

The authors had no disclosures to report. Watts has been an investigator, consultant, and speaker for Amgen outside of the published editorial. Hofbauer is on advisory boards for Alexion Pharmaceuticals, Amolyt Pharma, Amgen, and UCB. Langdahl has been a primary investigator on previous and ongoing clinical trials involving denosumab.

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.

A population-based study has shown a slightly elevated risk for patients’ developing skin disorders, including alopecia areata (AA), alopecia totalis (AT), vitiligo, and bullous pemphigoid (BP), more than 6 months after COVID-19 infection. In addition, the authors reported that COVID-19 vaccination appears to reduce these risks.

The study was published in JAMA Dermatology.

 

‘Compelling Evidence’

“This well-executed study by Heo et al provides compelling evidence to support an association between COVID-19 infection and the development of subsequent autoimmune and autoinflammatory skin diseases,” wrote authors led by Lisa M. Arkin, MD, of the Department of Dermatology, University of Wisconsin School of Medicine and Public Health in Madison, in an accompanying editorial.

Using databases from Korea’s National Health Insurance Service and the Korea Disease Control and Prevention Agency, investigators led by Yeon-Woo Heo, MD, a dermatology resident at Yonsei University Wonju College of Medicine, Wonju, Republic of Korea, compared 3.1 million people who had COVID-19 with 3.8 million controls, all with at least 180 days’ follow-up through December 31, 2022.

At a mean follow-up of 287 days in both cohorts, authors found significantly elevated risks for AA and vitiligo (adjusted hazard ratio [aHR], 1.11 for both), AT (aHR, 1.24), Behçet disease (aHR, 1.45), and BP (aHR, 1.62) in the post–COVID-19 cohort. The infection also raised the risk for other conditions such as systemic lupus erythematosus (aHR, 1.14) and Crohn’s disease (aHR, 1.35).

In subgroup analyses, demographic factors were associated with diverse effects: COVID-19 infection was associated with significantly higher odds of developing AA (for both men and women), vitiligo (men), Behçet disease (men and women), Crohn’s disease (men), ulcerative colitis (men), rheumatoid arthritis (men and women), systemic lupus erythematosus (men), ankylosing spondylitis (men), AT (women), and BP (women) than controls.

Those aged under 40 years were more likely to develop AA, primary cicatricial alopecia, Behçet disease, and ulcerative colitis, while those aged 40 years or older were more likely to develop AA, AT, vitiligo, Behçet disease, Crohn’s disease, rheumatoid arthritis, systemic lupus erythematosus, Sjögren’s syndrome, ankylosing spondylitis, and BP.

Additionally, severe COVID-19 requiring intensive care unit admission was associated with a significantly increased risk for autoimmune diseases, including AA, psoriasis, BP, and sarcoidosis. By timeframe, risks for AA, AT, and psoriasis were significantly higher during the initial Delta-dominant period.

 

Vaccination Effect

Moreover, vaccinated individuals were less likely to develop AA, AT, psoriasis, Behçet disease, and various nondermatologic conditions than were those who were unvaccinated. This finding, wrote Heo and colleagues, “may provide evidence to support the hypothesis that COVID-19 vaccines can help prevent autoimmune diseases.”

“That’s the part we all need to take into our offices tomorrow,” said Brett King, MD, PhD, a Fairfield, Connecticut–based dermatologist in private practice. He was not involved with the study but was asked to comment.

Overall, King said, the study carries two main messages. “The first is that COVID-19 infection increases the likelihood of developing an autoimmune or autoinflammatory disease in a large population.” The second and very important message is that being vaccinated against COVID-19 provides protection against developing an autoimmune or autoinflammatory disease.

“My concern is that the popular media highlights the first part,” said King, “and everybody who develops alopecia areata, vitiligo, or sarcoidosis blames COVID-19. That’s not what this work says.”

The foregoing distinction is especially important during the fall and winter, he added, when people getting influenza vaccines are routinely offered COVID-19 vaccines. “Many patients have said, ‘I got the COVID vaccine and developed alopecia areata 6 months later.’ Nearly everybody who has developed a new or worsening health condition in the last almost 5 years has had the perfect fall guy — the COVID vaccine or infection.”

With virtually all patients asking if they should get an updated COVID-19 vaccine or booster, he added, many report having heard that such vaccines cause AA, vitiligo, or other diseases. “To anchor these conversations in real data and not just anecdotes from a blog or Facebook is very useful,” said King, “and now we have very good data saying that the COVID vaccine is protective against these disorders.”

George Han, MD, PhD, associate professor of dermatology at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell in Hempstead, New York, applauds investigators’ use of a large, robust database but suggests interpreting results cautiously. He was not involved with the study but was asked to comment.

“You could do a large, well-done study,” Han said, “but it could still not necessarily be generalizable. These autoimmune conditions they’re looking at have clear ethnic and racial biases.” Heo and colleagues acknowledged shortcomings including their study population’s monomorphic nature.

Additional issues that limit the study’s impact, said Han, include the difficulty of conceptualizing a 10%-20% increase in conditions that at baseline are rare. And many of the findings reflected natural patterns, he said. For instance, BP more commonly affects older people, COVID-19 notwithstanding.

Han said that for him, the study’s main value going forward is helping to explain a rash of worsening inflammatory skin disease that many dermatologists saw early in the pandemic. “We would regularly see patients who were well controlled with, for example, psoriasis or eczema. But after COVID-19 infection or a vaccine (usually mRNA-type), in some cases they would come in flaring badly.” This happened at least a dozen times during the first year of post-shutdown appointments, he said.

“We’ve seen patients who have flared multiple times — they get the booster, then flare again,” Han added. Similar patterns occurred with pyoderma gangrenosum and other inflammatory skin diseases, he said.

Given the modest effect sizes of the associations reported in the Korean study, Arkin and colleagues wrote in their JAMA Dermatology editorial that surveillance for autoimmune disease is probably not warranted without new examination findings or symptoms. “For certain,” King said, “we should not go hunting for things that aren’t obviously there.”

Rather, Arkin and colleagues wrote, the higher autoimmunity rates seen among the unvaccinated, as well as during the Delta phase (when patients were sicker and hospitalizations were more likely) and in patients requiring intensive care, suggest that “interventions that reduce disease severity could also potentially reduce long-term risk of subsequent autoimmune sequelae.”

Future research addressing whether people with preexisting autoimmune conditions are at greater risk for flares or developing new autoimmune diseases following COVID-19 infection “would help to frame an evidence-based approach for patients with autoimmune disorders who develop COVID-19 infection, including the role for antiviral treatments,” they added.

The study was supported by grants from the Research Program of the Korea Medical Institute, the Korea Health Industry Development Institute, and the National Research Foundation of Korea. Han and King reported no relevant financial relationships. Arkin disclosed receiving research grants to her institution from Amgen and Eli Lilly, personal fees from Sanofi/Regeneron for consulting, and personal consulting fees from Merck outside the submitted work. Another author reported personal consulting fees from Dexcel Pharma and Honeydew outside the submitted work. No other disclosures were reported.

A version of this article appeared on Medscape.com.

A population-based study has shown a slightly elevated risk for patients’ developing skin disorders, including alopecia areata (AA), alopecia totalis (AT), vitiligo, and bullous pemphigoid (BP), more than 6 months after COVID-19 infection. In addition, the authors reported that COVID-19 vaccination appears to reduce these risks.

The study was published in JAMA Dermatology.

 

‘Compelling Evidence’

“This well-executed study by Heo et al provides compelling evidence to support an association between COVID-19 infection and the development of subsequent autoimmune and autoinflammatory skin diseases,” wrote authors led by Lisa M. Arkin, MD, of the Department of Dermatology, University of Wisconsin School of Medicine and Public Health in Madison, in an accompanying editorial.

Using databases from Korea’s National Health Insurance Service and the Korea Disease Control and Prevention Agency, investigators led by Yeon-Woo Heo, MD, a dermatology resident at Yonsei University Wonju College of Medicine, Wonju, Republic of Korea, compared 3.1 million people who had COVID-19 with 3.8 million controls, all with at least 180 days’ follow-up through December 31, 2022.

At a mean follow-up of 287 days in both cohorts, authors found significantly elevated risks for AA and vitiligo (adjusted hazard ratio [aHR], 1.11 for both), AT (aHR, 1.24), Behçet disease (aHR, 1.45), and BP (aHR, 1.62) in the post–COVID-19 cohort. The infection also raised the risk for other conditions such as systemic lupus erythematosus (aHR, 1.14) and Crohn’s disease (aHR, 1.35).

In subgroup analyses, demographic factors were associated with diverse effects: COVID-19 infection was associated with significantly higher odds of developing AA (for both men and women), vitiligo (men), Behçet disease (men and women), Crohn’s disease (men), ulcerative colitis (men), rheumatoid arthritis (men and women), systemic lupus erythematosus (men), ankylosing spondylitis (men), AT (women), and BP (women) than controls.

Those aged under 40 years were more likely to develop AA, primary cicatricial alopecia, Behçet disease, and ulcerative colitis, while those aged 40 years or older were more likely to develop AA, AT, vitiligo, Behçet disease, Crohn’s disease, rheumatoid arthritis, systemic lupus erythematosus, Sjögren’s syndrome, ankylosing spondylitis, and BP.

Additionally, severe COVID-19 requiring intensive care unit admission was associated with a significantly increased risk for autoimmune diseases, including AA, psoriasis, BP, and sarcoidosis. By timeframe, risks for AA, AT, and psoriasis were significantly higher during the initial Delta-dominant period.

 

Vaccination Effect

Moreover, vaccinated individuals were less likely to develop AA, AT, psoriasis, Behçet disease, and various nondermatologic conditions than were those who were unvaccinated. This finding, wrote Heo and colleagues, “may provide evidence to support the hypothesis that COVID-19 vaccines can help prevent autoimmune diseases.”

“That’s the part we all need to take into our offices tomorrow,” said Brett King, MD, PhD, a Fairfield, Connecticut–based dermatologist in private practice. He was not involved with the study but was asked to comment.

Overall, King said, the study carries two main messages. “The first is that COVID-19 infection increases the likelihood of developing an autoimmune or autoinflammatory disease in a large population.” The second and very important message is that being vaccinated against COVID-19 provides protection against developing an autoimmune or autoinflammatory disease.

“My concern is that the popular media highlights the first part,” said King, “and everybody who develops alopecia areata, vitiligo, or sarcoidosis blames COVID-19. That’s not what this work says.”

The foregoing distinction is especially important during the fall and winter, he added, when people getting influenza vaccines are routinely offered COVID-19 vaccines. “Many patients have said, ‘I got the COVID vaccine and developed alopecia areata 6 months later.’ Nearly everybody who has developed a new or worsening health condition in the last almost 5 years has had the perfect fall guy — the COVID vaccine or infection.”

With virtually all patients asking if they should get an updated COVID-19 vaccine or booster, he added, many report having heard that such vaccines cause AA, vitiligo, or other diseases. “To anchor these conversations in real data and not just anecdotes from a blog or Facebook is very useful,” said King, “and now we have very good data saying that the COVID vaccine is protective against these disorders.”

George Han, MD, PhD, associate professor of dermatology at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell in Hempstead, New York, applauds investigators’ use of a large, robust database but suggests interpreting results cautiously. He was not involved with the study but was asked to comment.

“You could do a large, well-done study,” Han said, “but it could still not necessarily be generalizable. These autoimmune conditions they’re looking at have clear ethnic and racial biases.” Heo and colleagues acknowledged shortcomings including their study population’s monomorphic nature.

Additional issues that limit the study’s impact, said Han, include the difficulty of conceptualizing a 10%-20% increase in conditions that at baseline are rare. And many of the findings reflected natural patterns, he said. For instance, BP more commonly affects older people, COVID-19 notwithstanding.

Han said that for him, the study’s main value going forward is helping to explain a rash of worsening inflammatory skin disease that many dermatologists saw early in the pandemic. “We would regularly see patients who were well controlled with, for example, psoriasis or eczema. But after COVID-19 infection or a vaccine (usually mRNA-type), in some cases they would come in flaring badly.” This happened at least a dozen times during the first year of post-shutdown appointments, he said.

“We’ve seen patients who have flared multiple times — they get the booster, then flare again,” Han added. Similar patterns occurred with pyoderma gangrenosum and other inflammatory skin diseases, he said.

Given the modest effect sizes of the associations reported in the Korean study, Arkin and colleagues wrote in their JAMA Dermatology editorial that surveillance for autoimmune disease is probably not warranted without new examination findings or symptoms. “For certain,” King said, “we should not go hunting for things that aren’t obviously there.”

Rather, Arkin and colleagues wrote, the higher autoimmunity rates seen among the unvaccinated, as well as during the Delta phase (when patients were sicker and hospitalizations were more likely) and in patients requiring intensive care, suggest that “interventions that reduce disease severity could also potentially reduce long-term risk of subsequent autoimmune sequelae.”

Future research addressing whether people with preexisting autoimmune conditions are at greater risk for flares or developing new autoimmune diseases following COVID-19 infection “would help to frame an evidence-based approach for patients with autoimmune disorders who develop COVID-19 infection, including the role for antiviral treatments,” they added.

The study was supported by grants from the Research Program of the Korea Medical Institute, the Korea Health Industry Development Institute, and the National Research Foundation of Korea. Han and King reported no relevant financial relationships. Arkin disclosed receiving research grants to her institution from Amgen and Eli Lilly, personal fees from Sanofi/Regeneron for consulting, and personal consulting fees from Merck outside the submitted work. Another author reported personal consulting fees from Dexcel Pharma and Honeydew outside the submitted work. No other disclosures were reported.

A version of this article appeared on Medscape.com.

A population-based study has shown a slightly elevated risk for patients’ developing skin disorders, including alopecia areata (AA), alopecia totalis (AT), vitiligo, and bullous pemphigoid (BP), more than 6 months after COVID-19 infection. In addition, the authors reported that COVID-19 vaccination appears to reduce these risks.

The study was published in JAMA Dermatology.

 

‘Compelling Evidence’

“This well-executed study by Heo et al provides compelling evidence to support an association between COVID-19 infection and the development of subsequent autoimmune and autoinflammatory skin diseases,” wrote authors led by Lisa M. Arkin, MD, of the Department of Dermatology, University of Wisconsin School of Medicine and Public Health in Madison, in an accompanying editorial.

Using databases from Korea’s National Health Insurance Service and the Korea Disease Control and Prevention Agency, investigators led by Yeon-Woo Heo, MD, a dermatology resident at Yonsei University Wonju College of Medicine, Wonju, Republic of Korea, compared 3.1 million people who had COVID-19 with 3.8 million controls, all with at least 180 days’ follow-up through December 31, 2022.

At a mean follow-up of 287 days in both cohorts, authors found significantly elevated risks for AA and vitiligo (adjusted hazard ratio [aHR], 1.11 for both), AT (aHR, 1.24), Behçet disease (aHR, 1.45), and BP (aHR, 1.62) in the post–COVID-19 cohort. The infection also raised the risk for other conditions such as systemic lupus erythematosus (aHR, 1.14) and Crohn’s disease (aHR, 1.35).

In subgroup analyses, demographic factors were associated with diverse effects: COVID-19 infection was associated with significantly higher odds of developing AA (for both men and women), vitiligo (men), Behçet disease (men and women), Crohn’s disease (men), ulcerative colitis (men), rheumatoid arthritis (men and women), systemic lupus erythematosus (men), ankylosing spondylitis (men), AT (women), and BP (women) than controls.

Those aged under 40 years were more likely to develop AA, primary cicatricial alopecia, Behçet disease, and ulcerative colitis, while those aged 40 years or older were more likely to develop AA, AT, vitiligo, Behçet disease, Crohn’s disease, rheumatoid arthritis, systemic lupus erythematosus, Sjögren’s syndrome, ankylosing spondylitis, and BP.

Additionally, severe COVID-19 requiring intensive care unit admission was associated with a significantly increased risk for autoimmune diseases, including AA, psoriasis, BP, and sarcoidosis. By timeframe, risks for AA, AT, and psoriasis were significantly higher during the initial Delta-dominant period.

 

Vaccination Effect

Moreover, vaccinated individuals were less likely to develop AA, AT, psoriasis, Behçet disease, and various nondermatologic conditions than were those who were unvaccinated. This finding, wrote Heo and colleagues, “may provide evidence to support the hypothesis that COVID-19 vaccines can help prevent autoimmune diseases.”

“That’s the part we all need to take into our offices tomorrow,” said Brett King, MD, PhD, a Fairfield, Connecticut–based dermatologist in private practice. He was not involved with the study but was asked to comment.

Overall, King said, the study carries two main messages. “The first is that COVID-19 infection increases the likelihood of developing an autoimmune or autoinflammatory disease in a large population.” The second and very important message is that being vaccinated against COVID-19 provides protection against developing an autoimmune or autoinflammatory disease.

“My concern is that the popular media highlights the first part,” said King, “and everybody who develops alopecia areata, vitiligo, or sarcoidosis blames COVID-19. That’s not what this work says.”

The foregoing distinction is especially important during the fall and winter, he added, when people getting influenza vaccines are routinely offered COVID-19 vaccines. “Many patients have said, ‘I got the COVID vaccine and developed alopecia areata 6 months later.’ Nearly everybody who has developed a new or worsening health condition in the last almost 5 years has had the perfect fall guy — the COVID vaccine or infection.”

With virtually all patients asking if they should get an updated COVID-19 vaccine or booster, he added, many report having heard that such vaccines cause AA, vitiligo, or other diseases. “To anchor these conversations in real data and not just anecdotes from a blog or Facebook is very useful,” said King, “and now we have very good data saying that the COVID vaccine is protective against these disorders.”

George Han, MD, PhD, associate professor of dermatology at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell in Hempstead, New York, applauds investigators’ use of a large, robust database but suggests interpreting results cautiously. He was not involved with the study but was asked to comment.

“You could do a large, well-done study,” Han said, “but it could still not necessarily be generalizable. These autoimmune conditions they’re looking at have clear ethnic and racial biases.” Heo and colleagues acknowledged shortcomings including their study population’s monomorphic nature.

Additional issues that limit the study’s impact, said Han, include the difficulty of conceptualizing a 10%-20% increase in conditions that at baseline are rare. And many of the findings reflected natural patterns, he said. For instance, BP more commonly affects older people, COVID-19 notwithstanding.

Han said that for him, the study’s main value going forward is helping to explain a rash of worsening inflammatory skin disease that many dermatologists saw early in the pandemic. “We would regularly see patients who were well controlled with, for example, psoriasis or eczema. But after COVID-19 infection or a vaccine (usually mRNA-type), in some cases they would come in flaring badly.” This happened at least a dozen times during the first year of post-shutdown appointments, he said.

“We’ve seen patients who have flared multiple times — they get the booster, then flare again,” Han added. Similar patterns occurred with pyoderma gangrenosum and other inflammatory skin diseases, he said.

Given the modest effect sizes of the associations reported in the Korean study, Arkin and colleagues wrote in their JAMA Dermatology editorial that surveillance for autoimmune disease is probably not warranted without new examination findings or symptoms. “For certain,” King said, “we should not go hunting for things that aren’t obviously there.”

Rather, Arkin and colleagues wrote, the higher autoimmunity rates seen among the unvaccinated, as well as during the Delta phase (when patients were sicker and hospitalizations were more likely) and in patients requiring intensive care, suggest that “interventions that reduce disease severity could also potentially reduce long-term risk of subsequent autoimmune sequelae.”

Future research addressing whether people with preexisting autoimmune conditions are at greater risk for flares or developing new autoimmune diseases following COVID-19 infection “would help to frame an evidence-based approach for patients with autoimmune disorders who develop COVID-19 infection, including the role for antiviral treatments,” they added.

The study was supported by grants from the Research Program of the Korea Medical Institute, the Korea Health Industry Development Institute, and the National Research Foundation of Korea. Han and King reported no relevant financial relationships. Arkin disclosed receiving research grants to her institution from Amgen and Eli Lilly, personal fees from Sanofi/Regeneron for consulting, and personal consulting fees from Merck outside the submitted work. Another author reported personal consulting fees from Dexcel Pharma and Honeydew outside the submitted work. No other disclosures were reported.

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.