Lupus & Connective Tissue Diseases

TOPLINE:

Both infliximab and adalimumab are safe and effective in achieving remission in patients with severe mucocutaneous Behçet syndrome, with adalimumab demonstrating a quicker response time; both drugs also improve quality of life and disease activity scores.

METHODOLOGY:

• Researchers conducted a phase 3 prospective study to evaluate the efficacy and safety of the anti–tumor necrosis factor–alpha agents infliximab and adalimumab in patients with Behçet syndrome presenting with mucocutaneous manifestations and inadequate response to prior treatments who were recruited from four Italian tertiary referral centers specializing in Behçet syndrome.
• Patients were randomly assigned to receive either 5 mg/kg intravenous infliximab at weeks 0, 2, and 6 and then every 6-8 weeks (n = 22; mean age, 46 years; 32% women) or 40 mg subcutaneous adalimumab every 2 weeks (n = 18; mean age, 48 years; 28% women) for 24 weeks.
• Patients were followed-up for an additional 12 weeks after the treatment period, with regular assessments of disease activity, safety, and adherence to treatment.
• The primary outcome was the time to response of mucocutaneous manifestations over 6 months; the secondary outcomes included relapse rates; quality of life, assessed using the Short-Form Health Survey 36; and disease activity, assessed using the Behçet Disease Current Activity Form.
• The safety and tolerability of the drugs were evaluated as the frequency of treatment-emergent adverse events (AEs) and serious AEs, monitored every 2 weeks.

TAKEAWAY:

• The resolution of mucocutaneous manifestations was achieved significantly more quickly with adalimumab than with infliximab, with a median time to response of 42 vs 152 days (P = .001); the proportion of responders was also higher in the adalimumab group than in the infliximab group (94% vs 64%; P = .023).
• Patients in the infliximab group had a higher risk for nonresponse (adjusted hazard ratio [HR], 3.33; P = .012) and relapse (adjusted HR, 7.57; P = .036) than those in the adalimumab group.
• Both infliximab and adalimumab significantly improved the quality of life in all dimensions (P < .05 for all) and disease activity scores (P < .001 for both) from baseline to the end of the study period, with no significant differences found between the groups.
• Two AEs were reported in the adalimumab group, one of which was serious (myocardial infarction); three nonserious AEs were reported in the infliximab group.

IN PRACTICE:

“ADA [adalimumab] and IFX [infliximab] were generally well tolerated and efficacious in patients with BS [Behçet syndrome] who showed an inadequate response to prior treatments with at least AZA [azathioprine] or CyA [cyclosporine],” the authors wrote. “Although a more detailed treat-to-target profile is yet to be better defined, [the study] results are also crucial in terms of prescriptiveness (currently off label), not only in Italy but also beyond national borders, as the evidence coming from real life still needs to be confirmed by growing data from clinical trials.”

SOURCE:

The study was led by Rosaria Talarico, MD, PhD, University of Pisa in Italy, and was published online in Annals of the Rheumatic Diseases.

LIMITATIONS:

The small sample size and the distinctive study design may have limited the generalizability of the findings.

DISCLOSURES:

This study was funded through a grant from the Italian Medicines Agency. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Both infliximab and adalimumab are safe and effective in achieving remission in patients with severe mucocutaneous Behçet syndrome, with adalimumab demonstrating a quicker response time; both drugs also improve quality of life and disease activity scores.

METHODOLOGY:

• Researchers conducted a phase 3 prospective study to evaluate the efficacy and safety of the anti–tumor necrosis factor–alpha agents infliximab and adalimumab in patients with Behçet syndrome presenting with mucocutaneous manifestations and inadequate response to prior treatments who were recruited from four Italian tertiary referral centers specializing in Behçet syndrome.
• Patients were randomly assigned to receive either 5 mg/kg intravenous infliximab at weeks 0, 2, and 6 and then every 6-8 weeks (n = 22; mean age, 46 years; 32% women) or 40 mg subcutaneous adalimumab every 2 weeks (n = 18; mean age, 48 years; 28% women) for 24 weeks.
• Patients were followed-up for an additional 12 weeks after the treatment period, with regular assessments of disease activity, safety, and adherence to treatment.
• The primary outcome was the time to response of mucocutaneous manifestations over 6 months; the secondary outcomes included relapse rates; quality of life, assessed using the Short-Form Health Survey 36; and disease activity, assessed using the Behçet Disease Current Activity Form.
• The safety and tolerability of the drugs were evaluated as the frequency of treatment-emergent adverse events (AEs) and serious AEs, monitored every 2 weeks.

TAKEAWAY:

• The resolution of mucocutaneous manifestations was achieved significantly more quickly with adalimumab than with infliximab, with a median time to response of 42 vs 152 days (P = .001); the proportion of responders was also higher in the adalimumab group than in the infliximab group (94% vs 64%; P = .023).
• Patients in the infliximab group had a higher risk for nonresponse (adjusted hazard ratio [HR], 3.33; P = .012) and relapse (adjusted HR, 7.57; P = .036) than those in the adalimumab group.
• Both infliximab and adalimumab significantly improved the quality of life in all dimensions (P < .05 for all) and disease activity scores (P < .001 for both) from baseline to the end of the study period, with no significant differences found between the groups.
• Two AEs were reported in the adalimumab group, one of which was serious (myocardial infarction); three nonserious AEs were reported in the infliximab group.

IN PRACTICE:

“ADA [adalimumab] and IFX [infliximab] were generally well tolerated and efficacious in patients with BS [Behçet syndrome] who showed an inadequate response to prior treatments with at least AZA [azathioprine] or CyA [cyclosporine],” the authors wrote. “Although a more detailed treat-to-target profile is yet to be better defined, [the study] results are also crucial in terms of prescriptiveness (currently off label), not only in Italy but also beyond national borders, as the evidence coming from real life still needs to be confirmed by growing data from clinical trials.”

SOURCE:

The study was led by Rosaria Talarico, MD, PhD, University of Pisa in Italy, and was published online in Annals of the Rheumatic Diseases.

LIMITATIONS:

The small sample size and the distinctive study design may have limited the generalizability of the findings.

DISCLOSURES:

This study was funded through a grant from the Italian Medicines Agency. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Both infliximab and adalimumab are safe and effective in achieving remission in patients with severe mucocutaneous Behçet syndrome, with adalimumab demonstrating a quicker response time; both drugs also improve quality of life and disease activity scores.

METHODOLOGY:

• Researchers conducted a phase 3 prospective study to evaluate the efficacy and safety of the anti–tumor necrosis factor–alpha agents infliximab and adalimumab in patients with Behçet syndrome presenting with mucocutaneous manifestations and inadequate response to prior treatments who were recruited from four Italian tertiary referral centers specializing in Behçet syndrome.
• Patients were randomly assigned to receive either 5 mg/kg intravenous infliximab at weeks 0, 2, and 6 and then every 6-8 weeks (n = 22; mean age, 46 years; 32% women) or 40 mg subcutaneous adalimumab every 2 weeks (n = 18; mean age, 48 years; 28% women) for 24 weeks.
• Patients were followed-up for an additional 12 weeks after the treatment period, with regular assessments of disease activity, safety, and adherence to treatment.
• The primary outcome was the time to response of mucocutaneous manifestations over 6 months; the secondary outcomes included relapse rates; quality of life, assessed using the Short-Form Health Survey 36; and disease activity, assessed using the Behçet Disease Current Activity Form.
• The safety and tolerability of the drugs were evaluated as the frequency of treatment-emergent adverse events (AEs) and serious AEs, monitored every 2 weeks.

TAKEAWAY:

• The resolution of mucocutaneous manifestations was achieved significantly more quickly with adalimumab than with infliximab, with a median time to response of 42 vs 152 days (P = .001); the proportion of responders was also higher in the adalimumab group than in the infliximab group (94% vs 64%; P = .023).
• Patients in the infliximab group had a higher risk for nonresponse (adjusted hazard ratio [HR], 3.33; P = .012) and relapse (adjusted HR, 7.57; P = .036) than those in the adalimumab group.
• Both infliximab and adalimumab significantly improved the quality of life in all dimensions (P < .05 for all) and disease activity scores (P < .001 for both) from baseline to the end of the study period, with no significant differences found between the groups.
• Two AEs were reported in the adalimumab group, one of which was serious (myocardial infarction); three nonserious AEs were reported in the infliximab group.

IN PRACTICE:

“ADA [adalimumab] and IFX [infliximab] were generally well tolerated and efficacious in patients with BS [Behçet syndrome] who showed an inadequate response to prior treatments with at least AZA [azathioprine] or CyA [cyclosporine],” the authors wrote. “Although a more detailed treat-to-target profile is yet to be better defined, [the study] results are also crucial in terms of prescriptiveness (currently off label), not only in Italy but also beyond national borders, as the evidence coming from real life still needs to be confirmed by growing data from clinical trials.”

SOURCE:

The study was led by Rosaria Talarico, MD, PhD, University of Pisa in Italy, and was published online in Annals of the Rheumatic Diseases.

LIMITATIONS:

The small sample size and the distinctive study design may have limited the generalizability of the findings.

DISCLOSURES:

This study was funded through a grant from the Italian Medicines Agency. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Patients with cutaneous lupus erythematosus (CLE) experienced improved symptoms with iberdomide, a cereblon modulator, added to standard lupus medications, particularly in subacute and chronic cases.

METHODOLOGY:

• Researchers conducted a randomized phase 2 trial to evaluate the efficacy and safety of iberdomide in 288 patients with CLE (mean age, 45 years; 97% women). Iberdomide is a cereblon modulator, which results in degradation of two transcription factors of immune cell development and homeostasis — Ikaros and Aiolos — that have been implicated in the genetic predisposition of systemic lupus.
• CLE Disease Area and Severity Index Activity (CLASI-A) endpoints included mean percent change from baseline and ≥ 50% reduction from baseline (CLASI-50), which were evaluated in all patients with baseline CLASI-A scores ≥ 8 and by CLE subtypes (acute, subacute, and chronic).
• At baseline, 56% of patients had acute CLE, 29% had chronic CLE, and 16% had subacute CLE; 28% of patients had a baseline CLASI-A score ≥ 8.
• Patients were randomly assigned to receive oral iberdomide (0.45 mg, 0.30 mg, 0.15 mg, or placebo daily) for 24 weeks while continuing standard lupus medications. At week 24, patients on placebo were rerandomized to iberdomide 0.45 mg or 0.30 mg once a day, while those on iberdomide continued their assigned dose through week 52.

TAKEAWAY:

• Among patients with baseline CLASI-A ≥ 8, the mean change in CLASI-A score from baseline at week 24 was −66.7% for those on iberdomide 0.45 mg vs −54.2% for placebo (P = .295).
• At week 24, patients with subacute CLE showed a significantly greater mean percent change from baseline in CLASI-A with iberdomide 0.45 mg vs placebo (−90.5% vs −51.2%; P = .007), while no significant differences were observed with the 0.45-mg dose vs placebo in patients with chronic or acute CLE.
• Overall, CLASI-50 responses were not significantly different among those on 0.45 mg vs placebo (55.6% vs 44.6%). The proportions of patients achieving CLASI-50 at week 24 were significantly greater for iberdomide 0.45 mg vs placebo for those with subacute CLE (91.7% vs 52.9%; P = .035) and chronic CLE (62.1% vs 27.8%; P = .029), but not for those with baseline CLASI-A ≥ 8 (66.7% vs 50%).
• More than 80% of patients had treatment-emergent adverse events (TEAEs), which were mostly mild to moderate. Over 2 years, the most common were urinary tract infections, upper respiratory tract infections, neutropenia, and nasopharyngitis. TEAEs leading to iberdomide discontinuation in one or more patients were neutropenia (n = 7), rash (n = 7), increased hepatic enzymes (n = 4), and deep vein thrombosis (n = 3).

IN PRACTICE:

“Data from this phase 2 trial of iberdomide in patients with SLE suggest that a greater proportion of patients with subacute or chronic CLE who received the higher dose of 0.45 mg iberdomide achieved CLASI-50 vs placebo. For the overall population, CLASI-50 response was not significantly different between treatment groups at week 24, partly due to a high placebo response that may have been driven by patients with acute CLE,” the authors wrote.

SOURCE:

The study was led by Victoria P. Werth, MD, of the University of Pennsylvania and the Veteran’s Administration Medical Center, both in Philadelphia, and was published online in the Journal of the American Academy of Dermatology.

LIMITATIONS:

The study included small patient subgroups for different CLE subtypes, which may affect the generalizability of the findings. CLE subtype was determined by the investigator without additional photographic adjudication. Additionally, the use of background lupus medications could have influenced the placebo group’s response, limiting the ability to observe the treatment effect of iberdomide monotherapy.

DISCLOSURES:

The study was funded by Bristol-Myers Squibb. Six authors reported being employed by Bristol-Myers Squibb, and several others reported consultancy and research support from various sources including Bristol-Myers Squibb.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Patients with cutaneous lupus erythematosus (CLE) experienced improved symptoms with iberdomide, a cereblon modulator, added to standard lupus medications, particularly in subacute and chronic cases.

METHODOLOGY:

• Researchers conducted a randomized phase 2 trial to evaluate the efficacy and safety of iberdomide in 288 patients with CLE (mean age, 45 years; 97% women). Iberdomide is a cereblon modulator, which results in degradation of two transcription factors of immune cell development and homeostasis — Ikaros and Aiolos — that have been implicated in the genetic predisposition of systemic lupus.
• CLE Disease Area and Severity Index Activity (CLASI-A) endpoints included mean percent change from baseline and ≥ 50% reduction from baseline (CLASI-50), which were evaluated in all patients with baseline CLASI-A scores ≥ 8 and by CLE subtypes (acute, subacute, and chronic).
• At baseline, 56% of patients had acute CLE, 29% had chronic CLE, and 16% had subacute CLE; 28% of patients had a baseline CLASI-A score ≥ 8.
• Patients were randomly assigned to receive oral iberdomide (0.45 mg, 0.30 mg, 0.15 mg, or placebo daily) for 24 weeks while continuing standard lupus medications. At week 24, patients on placebo were rerandomized to iberdomide 0.45 mg or 0.30 mg once a day, while those on iberdomide continued their assigned dose through week 52.

TAKEAWAY:

• Among patients with baseline CLASI-A ≥ 8, the mean change in CLASI-A score from baseline at week 24 was −66.7% for those on iberdomide 0.45 mg vs −54.2% for placebo (P = .295).
• At week 24, patients with subacute CLE showed a significantly greater mean percent change from baseline in CLASI-A with iberdomide 0.45 mg vs placebo (−90.5% vs −51.2%; P = .007), while no significant differences were observed with the 0.45-mg dose vs placebo in patients with chronic or acute CLE.
• Overall, CLASI-50 responses were not significantly different among those on 0.45 mg vs placebo (55.6% vs 44.6%). The proportions of patients achieving CLASI-50 at week 24 were significantly greater for iberdomide 0.45 mg vs placebo for those with subacute CLE (91.7% vs 52.9%; P = .035) and chronic CLE (62.1% vs 27.8%; P = .029), but not for those with baseline CLASI-A ≥ 8 (66.7% vs 50%).
• More than 80% of patients had treatment-emergent adverse events (TEAEs), which were mostly mild to moderate. Over 2 years, the most common were urinary tract infections, upper respiratory tract infections, neutropenia, and nasopharyngitis. TEAEs leading to iberdomide discontinuation in one or more patients were neutropenia (n = 7), rash (n = 7), increased hepatic enzymes (n = 4), and deep vein thrombosis (n = 3).

IN PRACTICE:

“Data from this phase 2 trial of iberdomide in patients with SLE suggest that a greater proportion of patients with subacute or chronic CLE who received the higher dose of 0.45 mg iberdomide achieved CLASI-50 vs placebo. For the overall population, CLASI-50 response was not significantly different between treatment groups at week 24, partly due to a high placebo response that may have been driven by patients with acute CLE,” the authors wrote.

SOURCE:

The study was led by Victoria P. Werth, MD, of the University of Pennsylvania and the Veteran’s Administration Medical Center, both in Philadelphia, and was published online in the Journal of the American Academy of Dermatology.

LIMITATIONS:

The study included small patient subgroups for different CLE subtypes, which may affect the generalizability of the findings. CLE subtype was determined by the investigator without additional photographic adjudication. Additionally, the use of background lupus medications could have influenced the placebo group’s response, limiting the ability to observe the treatment effect of iberdomide monotherapy.

DISCLOSURES:

The study was funded by Bristol-Myers Squibb. Six authors reported being employed by Bristol-Myers Squibb, and several others reported consultancy and research support from various sources including Bristol-Myers Squibb.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Patients with cutaneous lupus erythematosus (CLE) experienced improved symptoms with iberdomide, a cereblon modulator, added to standard lupus medications, particularly in subacute and chronic cases.

METHODOLOGY:

• Researchers conducted a randomized phase 2 trial to evaluate the efficacy and safety of iberdomide in 288 patients with CLE (mean age, 45 years; 97% women). Iberdomide is a cereblon modulator, which results in degradation of two transcription factors of immune cell development and homeostasis — Ikaros and Aiolos — that have been implicated in the genetic predisposition of systemic lupus.
• CLE Disease Area and Severity Index Activity (CLASI-A) endpoints included mean percent change from baseline and ≥ 50% reduction from baseline (CLASI-50), which were evaluated in all patients with baseline CLASI-A scores ≥ 8 and by CLE subtypes (acute, subacute, and chronic).
• At baseline, 56% of patients had acute CLE, 29% had chronic CLE, and 16% had subacute CLE; 28% of patients had a baseline CLASI-A score ≥ 8.
• Patients were randomly assigned to receive oral iberdomide (0.45 mg, 0.30 mg, 0.15 mg, or placebo daily) for 24 weeks while continuing standard lupus medications. At week 24, patients on placebo were rerandomized to iberdomide 0.45 mg or 0.30 mg once a day, while those on iberdomide continued their assigned dose through week 52.

TAKEAWAY:

• Among patients with baseline CLASI-A ≥ 8, the mean change in CLASI-A score from baseline at week 24 was −66.7% for those on iberdomide 0.45 mg vs −54.2% for placebo (P = .295).
• At week 24, patients with subacute CLE showed a significantly greater mean percent change from baseline in CLASI-A with iberdomide 0.45 mg vs placebo (−90.5% vs −51.2%; P = .007), while no significant differences were observed with the 0.45-mg dose vs placebo in patients with chronic or acute CLE.
• Overall, CLASI-50 responses were not significantly different among those on 0.45 mg vs placebo (55.6% vs 44.6%). The proportions of patients achieving CLASI-50 at week 24 were significantly greater for iberdomide 0.45 mg vs placebo for those with subacute CLE (91.7% vs 52.9%; P = .035) and chronic CLE (62.1% vs 27.8%; P = .029), but not for those with baseline CLASI-A ≥ 8 (66.7% vs 50%).
• More than 80% of patients had treatment-emergent adverse events (TEAEs), which were mostly mild to moderate. Over 2 years, the most common were urinary tract infections, upper respiratory tract infections, neutropenia, and nasopharyngitis. TEAEs leading to iberdomide discontinuation in one or more patients were neutropenia (n = 7), rash (n = 7), increased hepatic enzymes (n = 4), and deep vein thrombosis (n = 3).

IN PRACTICE:

“Data from this phase 2 trial of iberdomide in patients with SLE suggest that a greater proportion of patients with subacute or chronic CLE who received the higher dose of 0.45 mg iberdomide achieved CLASI-50 vs placebo. For the overall population, CLASI-50 response was not significantly different between treatment groups at week 24, partly due to a high placebo response that may have been driven by patients with acute CLE,” the authors wrote.

SOURCE:

The study was led by Victoria P. Werth, MD, of the University of Pennsylvania and the Veteran’s Administration Medical Center, both in Philadelphia, and was published online in the Journal of the American Academy of Dermatology.

LIMITATIONS:

The study included small patient subgroups for different CLE subtypes, which may affect the generalizability of the findings. CLE subtype was determined by the investigator without additional photographic adjudication. Additionally, the use of background lupus medications could have influenced the placebo group’s response, limiting the ability to observe the treatment effect of iberdomide monotherapy.

DISCLOSURES:

The study was funded by Bristol-Myers Squibb. Six authors reported being employed by Bristol-Myers Squibb, and several others reported consultancy and research support from various sources including Bristol-Myers Squibb.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

Many people with rheumatologic diseases try supplements for symptom relief. Here’s what you need to know about some common picks.

Dietary supplements were a $159 billion business in the United States in 2023, and many people with rheumatologic diseases are buying in. Research suggests more than 6 in 10 people with fibromyalgia, nearly 8 in 10 people with Sjögren’s disease, and more than 8 in 10 people with rheumatoid arthritis (RA) take dietary supplements.

Whatever the symptom — pain, swelling, or fatigue — you can probably find a supplement purporting to relieve it. But do these supplements work, and are they safe? A study review in RMD Open comprising 24 systematic reviews and 150 original articles suggests more high-quality research is needed on the effects of dietary supplements on rheumatologic diseases. Most studies have focused on RA or osteoarthritis (OA), where the evidence level is moderate at best.

Dr. Janet Funk

“The studies in this space are usually not very high quality because there’s no money to support them, among other things, plus the products are disparate,” said Janet Funk, MD, MS, professor in the School of Nutritional Sciences and Wellness at the University of Arizona, Tucson. She recommended brushing up on supplements and finding out what patients are taking so you can offer advice and watch for drug-supplement interactions.

When asked for a medication list, many patients forget to report supplements, Funk said. “You have to prompt them specifically. I think some physicians have very negative views about supplements because so little data is known, and patients might pick up on that and decide not to report their use.” She recommended saying something like: “To give you the best possible care, I want to know everything you’re taking, including supplements. The things I’m prescribing could maybe interact with the things you’re taking, so I want to make sure I know about all of it so that together we can figure out if the combination of things is safe.”

The quality of dietary supplements varies, and they aren’t regulated like drugs by the Food and Drug Administration. Funk recommended selecting products verified by NSF or ConsumerLab. They test supplements to ensure the label reflects what’s inside.

This news organization scoured the literature and asked experts to weigh in on the evidence behind popular supplements in rheumatology today.
 

The Essential Nutrients

Vitamin supplements are a staple in many homes — but are they helpful? “Individual vitamin supplements will not provide any benefit unless the person is deficient in a specific vitamin or mineral,” according to Elena Philippou, PhD, RD, associate professor of nutrition-dietetics at the University of Nicosia in Cyprus, and Elena Nikiphorou, MBBS, a rheumatologist at King’s College London in England. For some patients, deficiency is a reality. A retrospective cohort study in The Journal of Clinical Medicine found that people with RA were 17% more likely than age-matched control individuals to have nutrient deficiencies, perhaps because symptoms like fatigue, pain, and nausea affect their eating habits. Here’s what the science says about common vitamin supplements.

Dr. Elena Philippou

Vitamin D. This hormone-like vitamin, which attaches to receptors on immune cells to tamp down inflammation, was the most popular dietary supplement among rheumatology patients in a recent study from the United Kingdom. Vitamin D deficiency is common in people with RA, lupus, Sjögren’s disease, ankylosing spondylitis, systemic sclerosis, and fibromyalgia. In some cases, vitamin D levels track with disease activity, research suggests. Corticosteroids can also make vitamin D deficiency more likely. Can supplements help?

In RA, evidence points to small improvements. A systematic review of 11 studies including 3049 patients published in Nutrition Reviews showed that vitamin D supplements significantly reduced patients’ pain and Disease Activity Score in 28 joints (DAS28) using both C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR).

The research is mixed on the benefits of vitamin D supplementation for fibromyalgia symptoms, according to a study review in SN Comprehensive Clinical Medicine that included two studies and 80 patients on supplementation. However, researchers said it’s still worth discussing the potential benefits of taking vitamin D.

“Vitamin D supplementation is important in the context of various rheumatic diseases to prevent or treat bone disease,” said Philippou and Nikiphorou. “People with rheumatic disease should speak to their healthcare provider and ask to check their blood vitamin D concentration.” The results can help you recommend a dose.

Folate. Patients on methotrexate should take folic acid supplements under the guidance of a healthcare provider, said Philippou and Nikiphorou. The reason: Methotrexate can deplete folic acid levels, increasing the risk for side effects. An analysis of adverse event reports published showed that methotrexate users who took folic acid (or tumor necrosis factor–alpha inhibitors) had a reduced risk for hepatotoxicity or myelosuppression. A commonly recommended dose is 1 mg/d.

Vitamin B12. In a 2024 perspective paper in Rheumatology International, researchers said physicians should assess vitamin B12 levels early in the diagnostic process of rheumatologic diseases. One reason: Many symptoms of pernicious anemia, like fatigue, mimic symptoms of rheumatologic diseases. The gastrointestinal (GI) effects of systemic sclerosis could bring on vitamin B12 deficiency. In a small study in The Journal of Clinical Rheumatology, 44 of 62 patients with systemic sclerosis had low vitamin B12 levels.

Vitamin E. Vitamin E deficiency is rare in healthy adults. However, some medical conditions, like inflammatory bowel disease and malabsorption disorders, can make vitamin E deficiency more likely. In RA, a vitamin E supplement could help reduce joint swelling and sensitivity, according to a systematic review of nine studies including 39,845 patients in The European Journal of Clinical Nutrition. Researchers credit the nutrient’s role in aiding intestinal repair. Use with caution, as this supplement can increase bleeding risk in doses over 1000 mg/d.

Vitamin A. Like vitamin E, vitamin A deficiency is rare in the United States. The risk of oversupplementing is higher than undersupplementing. However, vitamin A deficiency can happen in people with chronic pancreatic, liver, or GI problems. In people with deficiency, a vitamin A supplement can help relieve dry eye symptoms common in Sjögren’s disease, suggests a narrative review published in Nutrients. Vitamin A might help reduce ocular surface changes by supporting the production of proteins that protect the outermost surfaces of the eyes. The recommended daily allowance for vitamin A is 900 μg. High-dose supplements can cause toxicity, resulting in GI symptoms and problems like lethargy, drowsiness, increased intracranial pressure, and skin changes.
 

The Replacements

These substances are similar to naturally occurring compounds in our bodies. The question is whether ingesting them yields benefits.

Glucosamine and chondroitin. Glucosamine and chondroitin occur naturally in our bodies and help us form and protect connective tissues. In pill form, this combo is the most popular dietary supplement for OA, according to research in the journal Maturitas. But studies of its effectiveness yield mixed results. A systematic review of 25 studies published in Inflammopharmacology showed that, in patients with knee OA, supplementation with about 1500 mg of glucosamine per day reduced tibiofemoral joint space narrowing, while supplementation with about 800 mg/d of chondroitin reduced pain intensity and improved physical function, compared with placebo. The duo of glucosamine and chondroitin did not bring significant benefits, perhaps because more studies are needed. Most side effects were mild, but some literature points to the potential for glucosamine to increase warfarin’s blood-thinning effects.

Omega-3 fatty acids. Fish oil is a top-selling supplement, and it might be helpful in inflammatory rheumatologic diseases. A systematic review of 30 studies including 710 patients published in Arthritis Research & Therapy showed that omega-3 fatty acid supplements can improve pain, swollen and tender joint count, DAS28 scores, and Health Assessment Questionnaire scores in patients with RA, psoriatic arthritis, or ankylosing spondylitis. In patients with lupus, a study review that included five studies and 284 patients in The International Journal of Environmental Research and Public Health suggested omega-3 fatty acid supplements could improve ESR, CRP, disease activity, inflammatory markers, oxidative stress, lipid levels, and endothelial function.

Omega-3 fatty acids have anti-inflammatory effects that might explain their benefits. In patients with RA, for example, fish oil supplementation was associated with elevated blood levels of resolvins and protectins, which help quell inflammation, according to a study in Prostaglandins, Leukotrienes and Essential Fatty Acids.

Philippou and Nikiphorou recommended combining food and supplements: Eat oily fish at least twice a week, regularly consume plant-based sources of omega-3s — like chia seeds, flaxseeds, or walnuts — and consider a daily supplement that contains 2 g of omega-3s from docosahexaenoic acid and eicosapentaenoic acid. Most fish oil side effects are mild, like heartburn and bad breath. Fish oil can have blood-thinning effects at high doses, so special attention is needed for patients on anticoagulants.

Probiotics. Building up the good bacteria in your gut might help you fight the effects of rheumatologic diseases. A systematic review of 80 randomized controlled trials in BMC Medicine suggested that therapies targeting the gut microbiota might improve the symptoms or inflammatory factors in celiac disease, lupus, juvenile idiopathic arthritis, psoriasis, Sjögren’s disease, multiple sclerosis, systemic sclerosis, Crohn’s disease, and ulcerative colitis. Probiotics were also shown to relieve pain in fibromyalgia, but they didn’t affect scores on the Fibromyalgia Impact Questionnaire. Probiotics were not helpful in spondyloarthritis or RA. There were no adverse events. By improving the balance of bacteria in the gut, probiotics might inhibit pro-inflammatory factors and signaling pathways and regulate CD4+ T-cell differentiation, the researchers wrote.

Not all probiotic supplements are created equal. Effects can vary by microorganism and dose. Until more high-quality studies are published, Philippou and Nikiphorou recommend daily consumption of probiotic food sources such as yogurt, kefir, sauerkraut, kimchi, tempeh, miso, and kombucha, along with prebiotic food sources such as bananas, onion, artichokes, asparagus, oats, leeks, and garlic.

Collagen. An increasingly popular supplement for hair, skin, and nails, some collagen peptide or hydrolyzed collagen supplements come with claims about joint health, too. Inside our bodies, collagen helps build joints. As a supplement, the jury is still out. A systematic review of 19 studies in The International Journal of Rheumatic Diseases suggested more research is needed to determine whether collagen supplements are harmful or helpful in OA or RA. Studies haven’t shown adverse events, and doses typically range from 2.5 to 15 g/d.

Coenzyme Q10 (CoQ10). This antioxidant occurs naturally in our cells and is produced through microbial fermentation for use in dietary supplements. A study review of 20 articles including 483 patients in Clinical Nutrition ESPEN concluded that CoQ10 supplementation up to 300 mg/d was beneficial in RA, fibromyalgia, or antiphospholipid syndrome (APS).

In RA, CoQ10 supplementation improved disease activity index, ESR, and cytokine levels and decreased malondialdehyde. CoQ10 might protect against the overproduction of reactive oxygen species that can promote inflammation and joint damage, the researchers said. In fibromyalgia, CoQ10 was linked with improvements in pain, fatigue, sleep, tender points count, mood disorders, and scores on the Fibromyalgia Impact Questionnaire in most of the included studies. CoQ10 might help in fibromyalgia by improving mitochondrial dysfunction. In APS, CoQ10 improved endothelial function and decreased prothrombotic and pro-inflammatory mediators. CoQ10 might change the expression of genes that promote atherosclerosis. A few patients had GI side effects like nausea and diarrhea, but the supplements were generally well tolerated.

Melatonin. Commonly touted as a sleep aid, this hormone has immune and anti-inflammatory activities that could benefit people with rheumatologic diseases. A study review of 13 articles including 533 patients in Clinical Nutrition ESPEN concluded that melatonin can help improve sleep, pain, and mood in fibromyalgia, OA, and osteoporosis but not in RA. Side effects were minimal, but a few people experienced nausea, drowsiness, nightmares, or headaches. Doses of 5-6 mg/d are likely safe for most adults.
 

The Plant-Derived Antioxidants

Many supplements used in rheumatology are antioxidants derived from herbs, spices, or other plants. When plants encounter stressors, like temperature changes or hungry insects, their secondary metabolism revs up and creates compounds with biological properties. Some of these substances influence inflammatory pathways in the human body, said Luís Silva, PhD, a medicinal chemistry researcher at the Polytechnic Institute of Guarda in Portugal. “If it is possible to reduce these kinds of anti-inflammatory processes, it is also possible that we could help people with inflammatory diseases to a good life, or a better life.”

Dr. Luís Silva

Turmeric and curcumin. You might see this supplement labeled as turmeric, a golden spice in curry powder, or curcumin, an antioxidant compound known as a curcuminoid in turmeric. Curcuminoids might reduce inflammation by scavenging free radicals and inhibiting enzymes that make prostaglandins, Silva said.

Turmeric is the most popular herbal supplement for people with RA, according to Funk’s research. A study review of six publications including 539 patients in Frontiers in Immunology showed that curcumin supplements improved RA patients’ ESR, DAS, swollen joint count, and tender joint count. Turmeric could help patients with OA, too. Patients with OA who took 1000 mg/d of curcumin improved their pain and function, according to a systematic review including 12 studies and 1438 participants in the journal Nutrients. In lupus, small studies are promising but inconclusive, suggested a study review in Frontiers in Immunology.

Watch patients taking turmeric and methotrexate closely, Funk said. Both have been associated with liver problems. Some users also experience GI symptoms like diarrhea because turmeric doesn’t absorb well in the GI tract.

Milk thistle (silymarin). This flowering plant is often marketed as a liver-supporting supplement, but research also suggests promise in RA and OA. A systematic review of 12 studies in Current Rheumatology Reviews suggested that silymarin supplements might help relieve pain, reduce inflammation, and protect the cartilage matrix, synovial membrane, and cartilage cells in joints. This supplement might help via immunomodulatory, anti-inflammatory, antioxidant, and anti-apoptotic properties, the researchers said. Doses of 250-750 mg appear to be safe. Side effects such as gastroenteritis, diarrhea, bloating, and headache can occur.

Boswellia serrata. Sourced from the resin of a tree that grows in dry, mountainous regions of Asia and Africa, Boswellia serrata can help relieve joint pain and stiffness and improve joint function in OA, suggested a systematic review of seven trials involving 545 patients in BMC Complementary Medicine and Therapies. Users saw benefits when taking 100-250 mg/d for 4 weeks or more. Compounds in Boswellia serrata may inhibit 5-lipoxygenase, an enzyme involved in producing inflammatory leukotrienes. No adverse events were reported. In some studies, users have reported GI side effects.

Ginger. Ginger is a popular herbal supplement among people with RA, Funk’s research suggested. One small clinical trial involving 70 patients with RA in the journal Gene showed that taking 1500 mg/d of ginger for 12 weeks improved their DAS and boosted their expression of FoxP3 genes, which are linked with the function of regulatory T cells. A meta-analysis including three studies with 330 patients taking ginger published in the journal Nutrients suggested ginger can reduce pain and systemic inflammation in people with OA. Preclinical studies suggested phenolic compounds in this spicy root, such as gingerols, reduce inflammation through multiple mechanisms.

Funk’s research revealed wide variation in the quality of ginger supplements, reinforcing the importance of selecting an independently verified product. Research suggested a safe dose is up to 2-2.5 g/kg body weight.

Resveratrol. Found in red grapes and red wine, this compound is particularly good at blocking COX-2 enzymes, an important step in the inflammatory cascade, Silva said. “Because of their chemical structure, they have great affinity to these enzymes to lead to their inhibition,” he said. A study review of five articles including 481 patients in The European Journal of Rheumatology showed that people with OA, RA, or Takayasu arteritis who took 250-1000 mg/d of resveratrol saw improvements in pain, function, disease activity, joint swelling, and inflammation, with no side effects.

Cinnamon. This warming spice is gaining popularity as a supplement, reported the American Botanical Council. Cinnamon is often marketed as lowering blood sugar and supporting bone health. In a small study of 36 women with RA published in The Journal of the American College of Nutrition, participants who consumed 2 g/d of cinnamon powder had reduced DASs along with reduced pain and tender and swollen joint counts. Cinnamon may reduce pain by inhibiting prostaglandin and blunt inflammation by reducing the release of arachidonic acid from cell membranes, according to a study review in Frontiers in Pharmacology. GI problems and allergic reactions are among the most common side effects.

Funk, Nikiphorou, Philippou, and Silva all had no relevant disclosures.

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

Many people with rheumatologic diseases try supplements for symptom relief. Here’s what you need to know about some common picks.

Dietary supplements were a $159 billion business in the United States in 2023, and many people with rheumatologic diseases are buying in. Research suggests more than 6 in 10 people with fibromyalgia, nearly 8 in 10 people with Sjögren’s disease, and more than 8 in 10 people with rheumatoid arthritis (RA) take dietary supplements.

Whatever the symptom — pain, swelling, or fatigue — you can probably find a supplement purporting to relieve it. But do these supplements work, and are they safe? A study review in RMD Open comprising 24 systematic reviews and 150 original articles suggests more high-quality research is needed on the effects of dietary supplements on rheumatologic diseases. Most studies have focused on RA or osteoarthritis (OA), where the evidence level is moderate at best.

Dr. Janet Funk

“The studies in this space are usually not very high quality because there’s no money to support them, among other things, plus the products are disparate,” said Janet Funk, MD, MS, professor in the School of Nutritional Sciences and Wellness at the University of Arizona, Tucson. She recommended brushing up on supplements and finding out what patients are taking so you can offer advice and watch for drug-supplement interactions.

When asked for a medication list, many patients forget to report supplements, Funk said. “You have to prompt them specifically. I think some physicians have very negative views about supplements because so little data is known, and patients might pick up on that and decide not to report their use.” She recommended saying something like: “To give you the best possible care, I want to know everything you’re taking, including supplements. The things I’m prescribing could maybe interact with the things you’re taking, so I want to make sure I know about all of it so that together we can figure out if the combination of things is safe.”

The quality of dietary supplements varies, and they aren’t regulated like drugs by the Food and Drug Administration. Funk recommended selecting products verified by NSF or ConsumerLab. They test supplements to ensure the label reflects what’s inside.

This news organization scoured the literature and asked experts to weigh in on the evidence behind popular supplements in rheumatology today.
 

The Essential Nutrients

Vitamin supplements are a staple in many homes — but are they helpful? “Individual vitamin supplements will not provide any benefit unless the person is deficient in a specific vitamin or mineral,” according to Elena Philippou, PhD, RD, associate professor of nutrition-dietetics at the University of Nicosia in Cyprus, and Elena Nikiphorou, MBBS, a rheumatologist at King’s College London in England. For some patients, deficiency is a reality. A retrospective cohort study in The Journal of Clinical Medicine found that people with RA were 17% more likely than age-matched control individuals to have nutrient deficiencies, perhaps because symptoms like fatigue, pain, and nausea affect their eating habits. Here’s what the science says about common vitamin supplements.

Dr. Elena Philippou

Vitamin D. This hormone-like vitamin, which attaches to receptors on immune cells to tamp down inflammation, was the most popular dietary supplement among rheumatology patients in a recent study from the United Kingdom. Vitamin D deficiency is common in people with RA, lupus, Sjögren’s disease, ankylosing spondylitis, systemic sclerosis, and fibromyalgia. In some cases, vitamin D levels track with disease activity, research suggests. Corticosteroids can also make vitamin D deficiency more likely. Can supplements help?

In RA, evidence points to small improvements. A systematic review of 11 studies including 3049 patients published in Nutrition Reviews showed that vitamin D supplements significantly reduced patients’ pain and Disease Activity Score in 28 joints (DAS28) using both C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR).

The research is mixed on the benefits of vitamin D supplementation for fibromyalgia symptoms, according to a study review in SN Comprehensive Clinical Medicine that included two studies and 80 patients on supplementation. However, researchers said it’s still worth discussing the potential benefits of taking vitamin D.

“Vitamin D supplementation is important in the context of various rheumatic diseases to prevent or treat bone disease,” said Philippou and Nikiphorou. “People with rheumatic disease should speak to their healthcare provider and ask to check their blood vitamin D concentration.” The results can help you recommend a dose.

Folate. Patients on methotrexate should take folic acid supplements under the guidance of a healthcare provider, said Philippou and Nikiphorou. The reason: Methotrexate can deplete folic acid levels, increasing the risk for side effects. An analysis of adverse event reports published showed that methotrexate users who took folic acid (or tumor necrosis factor–alpha inhibitors) had a reduced risk for hepatotoxicity or myelosuppression. A commonly recommended dose is 1 mg/d.

Vitamin B12. In a 2024 perspective paper in Rheumatology International, researchers said physicians should assess vitamin B12 levels early in the diagnostic process of rheumatologic diseases. One reason: Many symptoms of pernicious anemia, like fatigue, mimic symptoms of rheumatologic diseases. The gastrointestinal (GI) effects of systemic sclerosis could bring on vitamin B12 deficiency. In a small study in The Journal of Clinical Rheumatology, 44 of 62 patients with systemic sclerosis had low vitamin B12 levels.

Vitamin E. Vitamin E deficiency is rare in healthy adults. However, some medical conditions, like inflammatory bowel disease and malabsorption disorders, can make vitamin E deficiency more likely. In RA, a vitamin E supplement could help reduce joint swelling and sensitivity, according to a systematic review of nine studies including 39,845 patients in The European Journal of Clinical Nutrition. Researchers credit the nutrient’s role in aiding intestinal repair. Use with caution, as this supplement can increase bleeding risk in doses over 1000 mg/d.

Vitamin A. Like vitamin E, vitamin A deficiency is rare in the United States. The risk of oversupplementing is higher than undersupplementing. However, vitamin A deficiency can happen in people with chronic pancreatic, liver, or GI problems. In people with deficiency, a vitamin A supplement can help relieve dry eye symptoms common in Sjögren’s disease, suggests a narrative review published in Nutrients. Vitamin A might help reduce ocular surface changes by supporting the production of proteins that protect the outermost surfaces of the eyes. The recommended daily allowance for vitamin A is 900 μg. High-dose supplements can cause toxicity, resulting in GI symptoms and problems like lethargy, drowsiness, increased intracranial pressure, and skin changes.
 

The Replacements

These substances are similar to naturally occurring compounds in our bodies. The question is whether ingesting them yields benefits.

Glucosamine and chondroitin. Glucosamine and chondroitin occur naturally in our bodies and help us form and protect connective tissues. In pill form, this combo is the most popular dietary supplement for OA, according to research in the journal Maturitas. But studies of its effectiveness yield mixed results. A systematic review of 25 studies published in Inflammopharmacology showed that, in patients with knee OA, supplementation with about 1500 mg of glucosamine per day reduced tibiofemoral joint space narrowing, while supplementation with about 800 mg/d of chondroitin reduced pain intensity and improved physical function, compared with placebo. The duo of glucosamine and chondroitin did not bring significant benefits, perhaps because more studies are needed. Most side effects were mild, but some literature points to the potential for glucosamine to increase warfarin’s blood-thinning effects.

Omega-3 fatty acids. Fish oil is a top-selling supplement, and it might be helpful in inflammatory rheumatologic diseases. A systematic review of 30 studies including 710 patients published in Arthritis Research & Therapy showed that omega-3 fatty acid supplements can improve pain, swollen and tender joint count, DAS28 scores, and Health Assessment Questionnaire scores in patients with RA, psoriatic arthritis, or ankylosing spondylitis. In patients with lupus, a study review that included five studies and 284 patients in The International Journal of Environmental Research and Public Health suggested omega-3 fatty acid supplements could improve ESR, CRP, disease activity, inflammatory markers, oxidative stress, lipid levels, and endothelial function.

Omega-3 fatty acids have anti-inflammatory effects that might explain their benefits. In patients with RA, for example, fish oil supplementation was associated with elevated blood levels of resolvins and protectins, which help quell inflammation, according to a study in Prostaglandins, Leukotrienes and Essential Fatty Acids.

Philippou and Nikiphorou recommended combining food and supplements: Eat oily fish at least twice a week, regularly consume plant-based sources of omega-3s — like chia seeds, flaxseeds, or walnuts — and consider a daily supplement that contains 2 g of omega-3s from docosahexaenoic acid and eicosapentaenoic acid. Most fish oil side effects are mild, like heartburn and bad breath. Fish oil can have blood-thinning effects at high doses, so special attention is needed for patients on anticoagulants.

Probiotics. Building up the good bacteria in your gut might help you fight the effects of rheumatologic diseases. A systematic review of 80 randomized controlled trials in BMC Medicine suggested that therapies targeting the gut microbiota might improve the symptoms or inflammatory factors in celiac disease, lupus, juvenile idiopathic arthritis, psoriasis, Sjögren’s disease, multiple sclerosis, systemic sclerosis, Crohn’s disease, and ulcerative colitis. Probiotics were also shown to relieve pain in fibromyalgia, but they didn’t affect scores on the Fibromyalgia Impact Questionnaire. Probiotics were not helpful in spondyloarthritis or RA. There were no adverse events. By improving the balance of bacteria in the gut, probiotics might inhibit pro-inflammatory factors and signaling pathways and regulate CD4+ T-cell differentiation, the researchers wrote.

Not all probiotic supplements are created equal. Effects can vary by microorganism and dose. Until more high-quality studies are published, Philippou and Nikiphorou recommend daily consumption of probiotic food sources such as yogurt, kefir, sauerkraut, kimchi, tempeh, miso, and kombucha, along with prebiotic food sources such as bananas, onion, artichokes, asparagus, oats, leeks, and garlic.

Collagen. An increasingly popular supplement for hair, skin, and nails, some collagen peptide or hydrolyzed collagen supplements come with claims about joint health, too. Inside our bodies, collagen helps build joints. As a supplement, the jury is still out. A systematic review of 19 studies in The International Journal of Rheumatic Diseases suggested more research is needed to determine whether collagen supplements are harmful or helpful in OA or RA. Studies haven’t shown adverse events, and doses typically range from 2.5 to 15 g/d.

Coenzyme Q10 (CoQ10). This antioxidant occurs naturally in our cells and is produced through microbial fermentation for use in dietary supplements. A study review of 20 articles including 483 patients in Clinical Nutrition ESPEN concluded that CoQ10 supplementation up to 300 mg/d was beneficial in RA, fibromyalgia, or antiphospholipid syndrome (APS).

In RA, CoQ10 supplementation improved disease activity index, ESR, and cytokine levels and decreased malondialdehyde. CoQ10 might protect against the overproduction of reactive oxygen species that can promote inflammation and joint damage, the researchers said. In fibromyalgia, CoQ10 was linked with improvements in pain, fatigue, sleep, tender points count, mood disorders, and scores on the Fibromyalgia Impact Questionnaire in most of the included studies. CoQ10 might help in fibromyalgia by improving mitochondrial dysfunction. In APS, CoQ10 improved endothelial function and decreased prothrombotic and pro-inflammatory mediators. CoQ10 might change the expression of genes that promote atherosclerosis. A few patients had GI side effects like nausea and diarrhea, but the supplements were generally well tolerated.

Melatonin. Commonly touted as a sleep aid, this hormone has immune and anti-inflammatory activities that could benefit people with rheumatologic diseases. A study review of 13 articles including 533 patients in Clinical Nutrition ESPEN concluded that melatonin can help improve sleep, pain, and mood in fibromyalgia, OA, and osteoporosis but not in RA. Side effects were minimal, but a few people experienced nausea, drowsiness, nightmares, or headaches. Doses of 5-6 mg/d are likely safe for most adults.
 

The Plant-Derived Antioxidants

Many supplements used in rheumatology are antioxidants derived from herbs, spices, or other plants. When plants encounter stressors, like temperature changes or hungry insects, their secondary metabolism revs up and creates compounds with biological properties. Some of these substances influence inflammatory pathways in the human body, said Luís Silva, PhD, a medicinal chemistry researcher at the Polytechnic Institute of Guarda in Portugal. “If it is possible to reduce these kinds of anti-inflammatory processes, it is also possible that we could help people with inflammatory diseases to a good life, or a better life.”

Dr. Luís Silva

Turmeric and curcumin. You might see this supplement labeled as turmeric, a golden spice in curry powder, or curcumin, an antioxidant compound known as a curcuminoid in turmeric. Curcuminoids might reduce inflammation by scavenging free radicals and inhibiting enzymes that make prostaglandins, Silva said.

Turmeric is the most popular herbal supplement for people with RA, according to Funk’s research. A study review of six publications including 539 patients in Frontiers in Immunology showed that curcumin supplements improved RA patients’ ESR, DAS, swollen joint count, and tender joint count. Turmeric could help patients with OA, too. Patients with OA who took 1000 mg/d of curcumin improved their pain and function, according to a systematic review including 12 studies and 1438 participants in the journal Nutrients. In lupus, small studies are promising but inconclusive, suggested a study review in Frontiers in Immunology.

Watch patients taking turmeric and methotrexate closely, Funk said. Both have been associated with liver problems. Some users also experience GI symptoms like diarrhea because turmeric doesn’t absorb well in the GI tract.

Milk thistle (silymarin). This flowering plant is often marketed as a liver-supporting supplement, but research also suggests promise in RA and OA. A systematic review of 12 studies in Current Rheumatology Reviews suggested that silymarin supplements might help relieve pain, reduce inflammation, and protect the cartilage matrix, synovial membrane, and cartilage cells in joints. This supplement might help via immunomodulatory, anti-inflammatory, antioxidant, and anti-apoptotic properties, the researchers said. Doses of 250-750 mg appear to be safe. Side effects such as gastroenteritis, diarrhea, bloating, and headache can occur.

Boswellia serrata. Sourced from the resin of a tree that grows in dry, mountainous regions of Asia and Africa, Boswellia serrata can help relieve joint pain and stiffness and improve joint function in OA, suggested a systematic review of seven trials involving 545 patients in BMC Complementary Medicine and Therapies. Users saw benefits when taking 100-250 mg/d for 4 weeks or more. Compounds in Boswellia serrata may inhibit 5-lipoxygenase, an enzyme involved in producing inflammatory leukotrienes. No adverse events were reported. In some studies, users have reported GI side effects.

Ginger. Ginger is a popular herbal supplement among people with RA, Funk’s research suggested. One small clinical trial involving 70 patients with RA in the journal Gene showed that taking 1500 mg/d of ginger for 12 weeks improved their DAS and boosted their expression of FoxP3 genes, which are linked with the function of regulatory T cells. A meta-analysis including three studies with 330 patients taking ginger published in the journal Nutrients suggested ginger can reduce pain and systemic inflammation in people with OA. Preclinical studies suggested phenolic compounds in this spicy root, such as gingerols, reduce inflammation through multiple mechanisms.

Funk’s research revealed wide variation in the quality of ginger supplements, reinforcing the importance of selecting an independently verified product. Research suggested a safe dose is up to 2-2.5 g/kg body weight.

Resveratrol. Found in red grapes and red wine, this compound is particularly good at blocking COX-2 enzymes, an important step in the inflammatory cascade, Silva said. “Because of their chemical structure, they have great affinity to these enzymes to lead to their inhibition,” he said. A study review of five articles including 481 patients in The European Journal of Rheumatology showed that people with OA, RA, or Takayasu arteritis who took 250-1000 mg/d of resveratrol saw improvements in pain, function, disease activity, joint swelling, and inflammation, with no side effects.

Cinnamon. This warming spice is gaining popularity as a supplement, reported the American Botanical Council. Cinnamon is often marketed as lowering blood sugar and supporting bone health. In a small study of 36 women with RA published in The Journal of the American College of Nutrition, participants who consumed 2 g/d of cinnamon powder had reduced DASs along with reduced pain and tender and swollen joint counts. Cinnamon may reduce pain by inhibiting prostaglandin and blunt inflammation by reducing the release of arachidonic acid from cell membranes, according to a study review in Frontiers in Pharmacology. GI problems and allergic reactions are among the most common side effects.

Funk, Nikiphorou, Philippou, and Silva all had no relevant disclosures.

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

Many people with rheumatologic diseases try supplements for symptom relief. Here’s what you need to know about some common picks.

Dietary supplements were a $159 billion business in the United States in 2023, and many people with rheumatologic diseases are buying in. Research suggests more than 6 in 10 people with fibromyalgia, nearly 8 in 10 people with Sjögren’s disease, and more than 8 in 10 people with rheumatoid arthritis (RA) take dietary supplements.

Whatever the symptom — pain, swelling, or fatigue — you can probably find a supplement purporting to relieve it. But do these supplements work, and are they safe? A study review in RMD Open comprising 24 systematic reviews and 150 original articles suggests more high-quality research is needed on the effects of dietary supplements on rheumatologic diseases. Most studies have focused on RA or osteoarthritis (OA), where the evidence level is moderate at best.

Dr. Janet Funk

“The studies in this space are usually not very high quality because there’s no money to support them, among other things, plus the products are disparate,” said Janet Funk, MD, MS, professor in the School of Nutritional Sciences and Wellness at the University of Arizona, Tucson. She recommended brushing up on supplements and finding out what patients are taking so you can offer advice and watch for drug-supplement interactions.

When asked for a medication list, many patients forget to report supplements, Funk said. “You have to prompt them specifically. I think some physicians have very negative views about supplements because so little data is known, and patients might pick up on that and decide not to report their use.” She recommended saying something like: “To give you the best possible care, I want to know everything you’re taking, including supplements. The things I’m prescribing could maybe interact with the things you’re taking, so I want to make sure I know about all of it so that together we can figure out if the combination of things is safe.”

The quality of dietary supplements varies, and they aren’t regulated like drugs by the Food and Drug Administration. Funk recommended selecting products verified by NSF or ConsumerLab. They test supplements to ensure the label reflects what’s inside.

This news organization scoured the literature and asked experts to weigh in on the evidence behind popular supplements in rheumatology today.
 

The Essential Nutrients

Vitamin supplements are a staple in many homes — but are they helpful? “Individual vitamin supplements will not provide any benefit unless the person is deficient in a specific vitamin or mineral,” according to Elena Philippou, PhD, RD, associate professor of nutrition-dietetics at the University of Nicosia in Cyprus, and Elena Nikiphorou, MBBS, a rheumatologist at King’s College London in England. For some patients, deficiency is a reality. A retrospective cohort study in The Journal of Clinical Medicine found that people with RA were 17% more likely than age-matched control individuals to have nutrient deficiencies, perhaps because symptoms like fatigue, pain, and nausea affect their eating habits. Here’s what the science says about common vitamin supplements.

Dr. Elena Philippou

Vitamin D. This hormone-like vitamin, which attaches to receptors on immune cells to tamp down inflammation, was the most popular dietary supplement among rheumatology patients in a recent study from the United Kingdom. Vitamin D deficiency is common in people with RA, lupus, Sjögren’s disease, ankylosing spondylitis, systemic sclerosis, and fibromyalgia. In some cases, vitamin D levels track with disease activity, research suggests. Corticosteroids can also make vitamin D deficiency more likely. Can supplements help?

In RA, evidence points to small improvements. A systematic review of 11 studies including 3049 patients published in Nutrition Reviews showed that vitamin D supplements significantly reduced patients’ pain and Disease Activity Score in 28 joints (DAS28) using both C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR).

The research is mixed on the benefits of vitamin D supplementation for fibromyalgia symptoms, according to a study review in SN Comprehensive Clinical Medicine that included two studies and 80 patients on supplementation. However, researchers said it’s still worth discussing the potential benefits of taking vitamin D.

“Vitamin D supplementation is important in the context of various rheumatic diseases to prevent or treat bone disease,” said Philippou and Nikiphorou. “People with rheumatic disease should speak to their healthcare provider and ask to check their blood vitamin D concentration.” The results can help you recommend a dose.

Folate. Patients on methotrexate should take folic acid supplements under the guidance of a healthcare provider, said Philippou and Nikiphorou. The reason: Methotrexate can deplete folic acid levels, increasing the risk for side effects. An analysis of adverse event reports published showed that methotrexate users who took folic acid (or tumor necrosis factor–alpha inhibitors) had a reduced risk for hepatotoxicity or myelosuppression. A commonly recommended dose is 1 mg/d.

Vitamin B12. In a 2024 perspective paper in Rheumatology International, researchers said physicians should assess vitamin B12 levels early in the diagnostic process of rheumatologic diseases. One reason: Many symptoms of pernicious anemia, like fatigue, mimic symptoms of rheumatologic diseases. The gastrointestinal (GI) effects of systemic sclerosis could bring on vitamin B12 deficiency. In a small study in The Journal of Clinical Rheumatology, 44 of 62 patients with systemic sclerosis had low vitamin B12 levels.

Vitamin E. Vitamin E deficiency is rare in healthy adults. However, some medical conditions, like inflammatory bowel disease and malabsorption disorders, can make vitamin E deficiency more likely. In RA, a vitamin E supplement could help reduce joint swelling and sensitivity, according to a systematic review of nine studies including 39,845 patients in The European Journal of Clinical Nutrition. Researchers credit the nutrient’s role in aiding intestinal repair. Use with caution, as this supplement can increase bleeding risk in doses over 1000 mg/d.

Vitamin A. Like vitamin E, vitamin A deficiency is rare in the United States. The risk of oversupplementing is higher than undersupplementing. However, vitamin A deficiency can happen in people with chronic pancreatic, liver, or GI problems. In people with deficiency, a vitamin A supplement can help relieve dry eye symptoms common in Sjögren’s disease, suggests a narrative review published in Nutrients. Vitamin A might help reduce ocular surface changes by supporting the production of proteins that protect the outermost surfaces of the eyes. The recommended daily allowance for vitamin A is 900 μg. High-dose supplements can cause toxicity, resulting in GI symptoms and problems like lethargy, drowsiness, increased intracranial pressure, and skin changes.
 

The Replacements

These substances are similar to naturally occurring compounds in our bodies. The question is whether ingesting them yields benefits.

Glucosamine and chondroitin. Glucosamine and chondroitin occur naturally in our bodies and help us form and protect connective tissues. In pill form, this combo is the most popular dietary supplement for OA, according to research in the journal Maturitas. But studies of its effectiveness yield mixed results. A systematic review of 25 studies published in Inflammopharmacology showed that, in patients with knee OA, supplementation with about 1500 mg of glucosamine per day reduced tibiofemoral joint space narrowing, while supplementation with about 800 mg/d of chondroitin reduced pain intensity and improved physical function, compared with placebo. The duo of glucosamine and chondroitin did not bring significant benefits, perhaps because more studies are needed. Most side effects were mild, but some literature points to the potential for glucosamine to increase warfarin’s blood-thinning effects.

Omega-3 fatty acids. Fish oil is a top-selling supplement, and it might be helpful in inflammatory rheumatologic diseases. A systematic review of 30 studies including 710 patients published in Arthritis Research & Therapy showed that omega-3 fatty acid supplements can improve pain, swollen and tender joint count, DAS28 scores, and Health Assessment Questionnaire scores in patients with RA, psoriatic arthritis, or ankylosing spondylitis. In patients with lupus, a study review that included five studies and 284 patients in The International Journal of Environmental Research and Public Health suggested omega-3 fatty acid supplements could improve ESR, CRP, disease activity, inflammatory markers, oxidative stress, lipid levels, and endothelial function.

Omega-3 fatty acids have anti-inflammatory effects that might explain their benefits. In patients with RA, for example, fish oil supplementation was associated with elevated blood levels of resolvins and protectins, which help quell inflammation, according to a study in Prostaglandins, Leukotrienes and Essential Fatty Acids.

Philippou and Nikiphorou recommended combining food and supplements: Eat oily fish at least twice a week, regularly consume plant-based sources of omega-3s — like chia seeds, flaxseeds, or walnuts — and consider a daily supplement that contains 2 g of omega-3s from docosahexaenoic acid and eicosapentaenoic acid. Most fish oil side effects are mild, like heartburn and bad breath. Fish oil can have blood-thinning effects at high doses, so special attention is needed for patients on anticoagulants.

Probiotics. Building up the good bacteria in your gut might help you fight the effects of rheumatologic diseases. A systematic review of 80 randomized controlled trials in BMC Medicine suggested that therapies targeting the gut microbiota might improve the symptoms or inflammatory factors in celiac disease, lupus, juvenile idiopathic arthritis, psoriasis, Sjögren’s disease, multiple sclerosis, systemic sclerosis, Crohn’s disease, and ulcerative colitis. Probiotics were also shown to relieve pain in fibromyalgia, but they didn’t affect scores on the Fibromyalgia Impact Questionnaire. Probiotics were not helpful in spondyloarthritis or RA. There were no adverse events. By improving the balance of bacteria in the gut, probiotics might inhibit pro-inflammatory factors and signaling pathways and regulate CD4+ T-cell differentiation, the researchers wrote.

Not all probiotic supplements are created equal. Effects can vary by microorganism and dose. Until more high-quality studies are published, Philippou and Nikiphorou recommend daily consumption of probiotic food sources such as yogurt, kefir, sauerkraut, kimchi, tempeh, miso, and kombucha, along with prebiotic food sources such as bananas, onion, artichokes, asparagus, oats, leeks, and garlic.

Collagen. An increasingly popular supplement for hair, skin, and nails, some collagen peptide or hydrolyzed collagen supplements come with claims about joint health, too. Inside our bodies, collagen helps build joints. As a supplement, the jury is still out. A systematic review of 19 studies in The International Journal of Rheumatic Diseases suggested more research is needed to determine whether collagen supplements are harmful or helpful in OA or RA. Studies haven’t shown adverse events, and doses typically range from 2.5 to 15 g/d.

Coenzyme Q10 (CoQ10). This antioxidant occurs naturally in our cells and is produced through microbial fermentation for use in dietary supplements. A study review of 20 articles including 483 patients in Clinical Nutrition ESPEN concluded that CoQ10 supplementation up to 300 mg/d was beneficial in RA, fibromyalgia, or antiphospholipid syndrome (APS).

In RA, CoQ10 supplementation improved disease activity index, ESR, and cytokine levels and decreased malondialdehyde. CoQ10 might protect against the overproduction of reactive oxygen species that can promote inflammation and joint damage, the researchers said. In fibromyalgia, CoQ10 was linked with improvements in pain, fatigue, sleep, tender points count, mood disorders, and scores on the Fibromyalgia Impact Questionnaire in most of the included studies. CoQ10 might help in fibromyalgia by improving mitochondrial dysfunction. In APS, CoQ10 improved endothelial function and decreased prothrombotic and pro-inflammatory mediators. CoQ10 might change the expression of genes that promote atherosclerosis. A few patients had GI side effects like nausea and diarrhea, but the supplements were generally well tolerated.

Melatonin. Commonly touted as a sleep aid, this hormone has immune and anti-inflammatory activities that could benefit people with rheumatologic diseases. A study review of 13 articles including 533 patients in Clinical Nutrition ESPEN concluded that melatonin can help improve sleep, pain, and mood in fibromyalgia, OA, and osteoporosis but not in RA. Side effects were minimal, but a few people experienced nausea, drowsiness, nightmares, or headaches. Doses of 5-6 mg/d are likely safe for most adults.
 

The Plant-Derived Antioxidants

Many supplements used in rheumatology are antioxidants derived from herbs, spices, or other plants. When plants encounter stressors, like temperature changes or hungry insects, their secondary metabolism revs up and creates compounds with biological properties. Some of these substances influence inflammatory pathways in the human body, said Luís Silva, PhD, a medicinal chemistry researcher at the Polytechnic Institute of Guarda in Portugal. “If it is possible to reduce these kinds of anti-inflammatory processes, it is also possible that we could help people with inflammatory diseases to a good life, or a better life.”

Dr. Luís Silva

Turmeric and curcumin. You might see this supplement labeled as turmeric, a golden spice in curry powder, or curcumin, an antioxidant compound known as a curcuminoid in turmeric. Curcuminoids might reduce inflammation by scavenging free radicals and inhibiting enzymes that make prostaglandins, Silva said.

Turmeric is the most popular herbal supplement for people with RA, according to Funk’s research. A study review of six publications including 539 patients in Frontiers in Immunology showed that curcumin supplements improved RA patients’ ESR, DAS, swollen joint count, and tender joint count. Turmeric could help patients with OA, too. Patients with OA who took 1000 mg/d of curcumin improved their pain and function, according to a systematic review including 12 studies and 1438 participants in the journal Nutrients. In lupus, small studies are promising but inconclusive, suggested a study review in Frontiers in Immunology.

Watch patients taking turmeric and methotrexate closely, Funk said. Both have been associated with liver problems. Some users also experience GI symptoms like diarrhea because turmeric doesn’t absorb well in the GI tract.

Milk thistle (silymarin). This flowering plant is often marketed as a liver-supporting supplement, but research also suggests promise in RA and OA. A systematic review of 12 studies in Current Rheumatology Reviews suggested that silymarin supplements might help relieve pain, reduce inflammation, and protect the cartilage matrix, synovial membrane, and cartilage cells in joints. This supplement might help via immunomodulatory, anti-inflammatory, antioxidant, and anti-apoptotic properties, the researchers said. Doses of 250-750 mg appear to be safe. Side effects such as gastroenteritis, diarrhea, bloating, and headache can occur.

Boswellia serrata. Sourced from the resin of a tree that grows in dry, mountainous regions of Asia and Africa, Boswellia serrata can help relieve joint pain and stiffness and improve joint function in OA, suggested a systematic review of seven trials involving 545 patients in BMC Complementary Medicine and Therapies. Users saw benefits when taking 100-250 mg/d for 4 weeks or more. Compounds in Boswellia serrata may inhibit 5-lipoxygenase, an enzyme involved in producing inflammatory leukotrienes. No adverse events were reported. In some studies, users have reported GI side effects.

Ginger. Ginger is a popular herbal supplement among people with RA, Funk’s research suggested. One small clinical trial involving 70 patients with RA in the journal Gene showed that taking 1500 mg/d of ginger for 12 weeks improved their DAS and boosted their expression of FoxP3 genes, which are linked with the function of regulatory T cells. A meta-analysis including three studies with 330 patients taking ginger published in the journal Nutrients suggested ginger can reduce pain and systemic inflammation in people with OA. Preclinical studies suggested phenolic compounds in this spicy root, such as gingerols, reduce inflammation through multiple mechanisms.

Funk’s research revealed wide variation in the quality of ginger supplements, reinforcing the importance of selecting an independently verified product. Research suggested a safe dose is up to 2-2.5 g/kg body weight.

Resveratrol. Found in red grapes and red wine, this compound is particularly good at blocking COX-2 enzymes, an important step in the inflammatory cascade, Silva said. “Because of their chemical structure, they have great affinity to these enzymes to lead to their inhibition,” he said. A study review of five articles including 481 patients in The European Journal of Rheumatology showed that people with OA, RA, or Takayasu arteritis who took 250-1000 mg/d of resveratrol saw improvements in pain, function, disease activity, joint swelling, and inflammation, with no side effects.

Cinnamon. This warming spice is gaining popularity as a supplement, reported the American Botanical Council. Cinnamon is often marketed as lowering blood sugar and supporting bone health. In a small study of 36 women with RA published in The Journal of the American College of Nutrition, participants who consumed 2 g/d of cinnamon powder had reduced DASs along with reduced pain and tender and swollen joint counts. Cinnamon may reduce pain by inhibiting prostaglandin and blunt inflammation by reducing the release of arachidonic acid from cell membranes, according to a study review in Frontiers in Pharmacology. GI problems and allergic reactions are among the most common side effects.

Funk, Nikiphorou, Philippou, and Silva all had no relevant disclosures.

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

TOPLINE: 

In patients with giant cell arteritis (GCA), intravenous methylprednisolone compared with oral glucocorticoids alone does not improve visual acuity and increases the risk for diabetes within the first year. Survival rates do not differ with these two treatments.

METHODOLOGY:

• Researchers conducted a population-based retrospective study at three centers in Sweden to assess the clinical characteristics, treatment-related toxicity, and mortality in patients with GCA who were receiving high-dose intravenous methylprednisolone.
• A total of 419 patients with biopsy-confirmed GCA (mean age at diagnosis, 75 years; 69% women) diagnosed from 2004 to 2019 were included.
• Patients were treated with either intravenous methylprednisolone (n = 111) at a dose of 500-1000 mg per day for 3 consecutive days or oral glucocorticoids alone (n = 308).
• Ischemic visual complications considered to indicate visual involvement were confirmed by an ophthalmologist, and data on visual acuity were collected from ophthalmologic clinic records at initial consultations and follow-up at 3-18 months.

TAKEAWAY:

• Despite a tendency toward improvement, no significant difference in visual acuity was observed with intravenous methylprednisolone compared with oral glucocorticoids.
• Patients treated with intravenous methylprednisolone had a higher risk for newly diagnosed diabetes within a year of GCA diagnosis (odds ratio [OR], 2.59; P = .01).
• The risk for diabetes remained elevated even after adjustment for the cumulative oral glucocorticoid dose at 3 months (adjusted OR, 3.30; P = .01).
• Survival rates did not significantly differ between the treatment groups over a mean follow-up of 6.6 years.

IN PRACTICE:

“In this study on the use of intravenous methylprednisolone treatment in GCA, we found no evidence of a beneficial effect in improving visual acuity or enabling more rapid tapering of the oral glucocorticoid dose,” the authors wrote. “The use of IVMP [intravenous methylprednisolone] was associated with an increased risk of diabetes during the first year compared with oral GC [glucocorticoid], raising questions about the value of IVMP in GCA treatment.”

SOURCE:

The study, led by Hampus Henningson, Department of Clinical Sciences, Rheumatology, Lund University, Lund, Sweden, was published online in Rheumatology.

LIMITATIONS: 

The retrospective nature of the study may have resulted in missing data and difficulty in accurately quantifying the cumulative glucocorticoid doses. The study did not validate the diagnoses of comorbidities but relied solely on diagnostic codes.

DISCLOSURES:

This study was supported by the Swedish Research Council, Swedish Rheumatism Association, Swedish Medical Society, Alfred Österlund’s Foundation, and King Gustaf V’s 80-year foundation. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE: 

In patients with giant cell arteritis (GCA), intravenous methylprednisolone compared with oral glucocorticoids alone does not improve visual acuity and increases the risk for diabetes within the first year. Survival rates do not differ with these two treatments.

METHODOLOGY:

• Researchers conducted a population-based retrospective study at three centers in Sweden to assess the clinical characteristics, treatment-related toxicity, and mortality in patients with GCA who were receiving high-dose intravenous methylprednisolone.
• A total of 419 patients with biopsy-confirmed GCA (mean age at diagnosis, 75 years; 69% women) diagnosed from 2004 to 2019 were included.
• Patients were treated with either intravenous methylprednisolone (n = 111) at a dose of 500-1000 mg per day for 3 consecutive days or oral glucocorticoids alone (n = 308).
• Ischemic visual complications considered to indicate visual involvement were confirmed by an ophthalmologist, and data on visual acuity were collected from ophthalmologic clinic records at initial consultations and follow-up at 3-18 months.

TAKEAWAY:

• Despite a tendency toward improvement, no significant difference in visual acuity was observed with intravenous methylprednisolone compared with oral glucocorticoids.
• Patients treated with intravenous methylprednisolone had a higher risk for newly diagnosed diabetes within a year of GCA diagnosis (odds ratio [OR], 2.59; P = .01).
• The risk for diabetes remained elevated even after adjustment for the cumulative oral glucocorticoid dose at 3 months (adjusted OR, 3.30; P = .01).
• Survival rates did not significantly differ between the treatment groups over a mean follow-up of 6.6 years.

IN PRACTICE:

“In this study on the use of intravenous methylprednisolone treatment in GCA, we found no evidence of a beneficial effect in improving visual acuity or enabling more rapid tapering of the oral glucocorticoid dose,” the authors wrote. “The use of IVMP [intravenous methylprednisolone] was associated with an increased risk of diabetes during the first year compared with oral GC [glucocorticoid], raising questions about the value of IVMP in GCA treatment.”

SOURCE:

The study, led by Hampus Henningson, Department of Clinical Sciences, Rheumatology, Lund University, Lund, Sweden, was published online in Rheumatology.

LIMITATIONS: 

The retrospective nature of the study may have resulted in missing data and difficulty in accurately quantifying the cumulative glucocorticoid doses. The study did not validate the diagnoses of comorbidities but relied solely on diagnostic codes.

DISCLOSURES:

This study was supported by the Swedish Research Council, Swedish Rheumatism Association, Swedish Medical Society, Alfred Österlund’s Foundation, and King Gustaf V’s 80-year foundation. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE: 

In patients with giant cell arteritis (GCA), intravenous methylprednisolone compared with oral glucocorticoids alone does not improve visual acuity and increases the risk for diabetes within the first year. Survival rates do not differ with these two treatments.

METHODOLOGY:

• Researchers conducted a population-based retrospective study at three centers in Sweden to assess the clinical characteristics, treatment-related toxicity, and mortality in patients with GCA who were receiving high-dose intravenous methylprednisolone.
• A total of 419 patients with biopsy-confirmed GCA (mean age at diagnosis, 75 years; 69% women) diagnosed from 2004 to 2019 were included.
• Patients were treated with either intravenous methylprednisolone (n = 111) at a dose of 500-1000 mg per day for 3 consecutive days or oral glucocorticoids alone (n = 308).
• Ischemic visual complications considered to indicate visual involvement were confirmed by an ophthalmologist, and data on visual acuity were collected from ophthalmologic clinic records at initial consultations and follow-up at 3-18 months.

TAKEAWAY:

• Despite a tendency toward improvement, no significant difference in visual acuity was observed with intravenous methylprednisolone compared with oral glucocorticoids.
• Patients treated with intravenous methylprednisolone had a higher risk for newly diagnosed diabetes within a year of GCA diagnosis (odds ratio [OR], 2.59; P = .01).
• The risk for diabetes remained elevated even after adjustment for the cumulative oral glucocorticoid dose at 3 months (adjusted OR, 3.30; P = .01).
• Survival rates did not significantly differ between the treatment groups over a mean follow-up of 6.6 years.

IN PRACTICE:

“In this study on the use of intravenous methylprednisolone treatment in GCA, we found no evidence of a beneficial effect in improving visual acuity or enabling more rapid tapering of the oral glucocorticoid dose,” the authors wrote. “The use of IVMP [intravenous methylprednisolone] was associated with an increased risk of diabetes during the first year compared with oral GC [glucocorticoid], raising questions about the value of IVMP in GCA treatment.”

SOURCE:

The study, led by Hampus Henningson, Department of Clinical Sciences, Rheumatology, Lund University, Lund, Sweden, was published online in Rheumatology.

LIMITATIONS: 

The retrospective nature of the study may have resulted in missing data and difficulty in accurately quantifying the cumulative glucocorticoid doses. The study did not validate the diagnoses of comorbidities but relied solely on diagnostic codes.

DISCLOSURES:

This study was supported by the Swedish Research Council, Swedish Rheumatism Association, Swedish Medical Society, Alfred Österlund’s Foundation, and King Gustaf V’s 80-year foundation. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

Nearly two thirds of patients with rheumatic conditions switched to medical cannabis from medications such as nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids, with the substitution being associated with greater self-reported improvement in symptoms than nonsubstitution.

METHODOLOGY:

• Researchers conducted a secondary analysis of a cross-sectional survey to investigate the prevalence of switching to medical cannabis from traditional medications in patients with rheumatic conditions from the United States and Canada.
• The survey included questions on current and past medical cannabis use, sociodemographic characteristics, medication taken and substituted, substance use, and patient-reported outcomes.
• Of the 1727 patients who completed the survey, 763 patients (mean age, 59 years; 84.1% women) reported current use of cannabis and were included in this analysis.
• Participants were asked if they had substituted any medications with medical cannabis and were sub-grouped accordingly.
• They also reported any changes in symptoms after initiating cannabis, the current and anticipated duration of medical cannabis use, methods of ingestion, cannabinoid content, and frequency of use.

TAKEAWAY:

• Overall, 62.5% reported substituting medical cannabis for certain medications, including NSAIDs (54.7%), opioids (48.6%), sleep aids (29.6%), muscle relaxants (25.2%), benzodiazepines (15.5%), and gabapentinoids (10.5%).
• The most common reasons given for substituting medical cannabis were fewer side effects (39%), better symptom control (27%), and fewer adverse effects (12%).
• Participants who substituted medical cannabis reported significant improvements in symptoms such as pain, sleep, joint stiffness, muscle spasms, and inflammation, and in overall health, compared with those who did not substitute it for medications.
• The substitution group was more likely to use inhalation methods (smoking and vaporizing) than the nonsubstitution group; they also used medical cannabis more frequently and preferred products containing delta-9-tetrahydrocannabinol.

IN PRACTICE:

“The changing legal status of cannabis has allowed a greater openness with more people willing to try cannabis for symptom relief. These encouraging results of medication reduction and favorable effect of [medical cannabis] require confirmation with more rigorous methods. At this time, survey information may be seen as a signal for effect, rather than sound evidence that could be applicable to those with musculoskeletal complaints in general,” the authors wrote. 

SOURCE:

The study was led by Kevin F. Boehnke, PhD, University of Michigan Medical School, Ann Arbor, and was published online in ACR Open Rheumatology.

LIMITATIONS: 

The cross-sectional nature of the study limited the determination of causality between medical cannabis use and symptom improvement. Moreover, the anonymous and self-reported nature of the survey at a single timepoint may have introduced recall bias. The sample predominantly consisted of older, White females, which may have limited the generalizability of the findings to other demographic groups.

DISCLOSURES:

Some authors received grant support from the National Institute on Drug Abuse and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Some others received payments, honoraria, grant funding, consulting fees, and travel support, and reported other ties with pharmaceutical companies and other institutions.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

Nearly two thirds of patients with rheumatic conditions switched to medical cannabis from medications such as nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids, with the substitution being associated with greater self-reported improvement in symptoms than nonsubstitution.

METHODOLOGY:

• Researchers conducted a secondary analysis of a cross-sectional survey to investigate the prevalence of switching to medical cannabis from traditional medications in patients with rheumatic conditions from the United States and Canada.
• The survey included questions on current and past medical cannabis use, sociodemographic characteristics, medication taken and substituted, substance use, and patient-reported outcomes.
• Of the 1727 patients who completed the survey, 763 patients (mean age, 59 years; 84.1% women) reported current use of cannabis and were included in this analysis.
• Participants were asked if they had substituted any medications with medical cannabis and were sub-grouped accordingly.
• They also reported any changes in symptoms after initiating cannabis, the current and anticipated duration of medical cannabis use, methods of ingestion, cannabinoid content, and frequency of use.

TAKEAWAY:

• Overall, 62.5% reported substituting medical cannabis for certain medications, including NSAIDs (54.7%), opioids (48.6%), sleep aids (29.6%), muscle relaxants (25.2%), benzodiazepines (15.5%), and gabapentinoids (10.5%).
• The most common reasons given for substituting medical cannabis were fewer side effects (39%), better symptom control (27%), and fewer adverse effects (12%).
• Participants who substituted medical cannabis reported significant improvements in symptoms such as pain, sleep, joint stiffness, muscle spasms, and inflammation, and in overall health, compared with those who did not substitute it for medications.
• The substitution group was more likely to use inhalation methods (smoking and vaporizing) than the nonsubstitution group; they also used medical cannabis more frequently and preferred products containing delta-9-tetrahydrocannabinol.

IN PRACTICE:

“The changing legal status of cannabis has allowed a greater openness with more people willing to try cannabis for symptom relief. These encouraging results of medication reduction and favorable effect of [medical cannabis] require confirmation with more rigorous methods. At this time, survey information may be seen as a signal for effect, rather than sound evidence that could be applicable to those with musculoskeletal complaints in general,” the authors wrote. 

SOURCE:

The study was led by Kevin F. Boehnke, PhD, University of Michigan Medical School, Ann Arbor, and was published online in ACR Open Rheumatology.

LIMITATIONS: 

The cross-sectional nature of the study limited the determination of causality between medical cannabis use and symptom improvement. Moreover, the anonymous and self-reported nature of the survey at a single timepoint may have introduced recall bias. The sample predominantly consisted of older, White females, which may have limited the generalizability of the findings to other demographic groups.

DISCLOSURES:

Some authors received grant support from the National Institute on Drug Abuse and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Some others received payments, honoraria, grant funding, consulting fees, and travel support, and reported other ties with pharmaceutical companies and other institutions.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

Nearly two thirds of patients with rheumatic conditions switched to medical cannabis from medications such as nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids, with the substitution being associated with greater self-reported improvement in symptoms than nonsubstitution.

METHODOLOGY:

• Researchers conducted a secondary analysis of a cross-sectional survey to investigate the prevalence of switching to medical cannabis from traditional medications in patients with rheumatic conditions from the United States and Canada.
• The survey included questions on current and past medical cannabis use, sociodemographic characteristics, medication taken and substituted, substance use, and patient-reported outcomes.
• Of the 1727 patients who completed the survey, 763 patients (mean age, 59 years; 84.1% women) reported current use of cannabis and were included in this analysis.
• Participants were asked if they had substituted any medications with medical cannabis and were sub-grouped accordingly.
• They also reported any changes in symptoms after initiating cannabis, the current and anticipated duration of medical cannabis use, methods of ingestion, cannabinoid content, and frequency of use.

TAKEAWAY:

• Overall, 62.5% reported substituting medical cannabis for certain medications, including NSAIDs (54.7%), opioids (48.6%), sleep aids (29.6%), muscle relaxants (25.2%), benzodiazepines (15.5%), and gabapentinoids (10.5%).
• The most common reasons given for substituting medical cannabis were fewer side effects (39%), better symptom control (27%), and fewer adverse effects (12%).
• Participants who substituted medical cannabis reported significant improvements in symptoms such as pain, sleep, joint stiffness, muscle spasms, and inflammation, and in overall health, compared with those who did not substitute it for medications.
• The substitution group was more likely to use inhalation methods (smoking and vaporizing) than the nonsubstitution group; they also used medical cannabis more frequently and preferred products containing delta-9-tetrahydrocannabinol.

IN PRACTICE:

“The changing legal status of cannabis has allowed a greater openness with more people willing to try cannabis for symptom relief. These encouraging results of medication reduction and favorable effect of [medical cannabis] require confirmation with more rigorous methods. At this time, survey information may be seen as a signal for effect, rather than sound evidence that could be applicable to those with musculoskeletal complaints in general,” the authors wrote. 

SOURCE:

The study was led by Kevin F. Boehnke, PhD, University of Michigan Medical School, Ann Arbor, and was published online in ACR Open Rheumatology.

LIMITATIONS: 

The cross-sectional nature of the study limited the determination of causality between medical cannabis use and symptom improvement. Moreover, the anonymous and self-reported nature of the survey at a single timepoint may have introduced recall bias. The sample predominantly consisted of older, White females, which may have limited the generalizability of the findings to other demographic groups.

DISCLOSURES:

Some authors received grant support from the National Institute on Drug Abuse and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Some others received payments, honoraria, grant funding, consulting fees, and travel support, and reported other ties with pharmaceutical companies and other institutions.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

Therapeutic drug monitoring (TDM) — the practice of using laboratory testing to measure blood levels of drugs — has garnered growing interest among rheumatologists in managing patients on disease-modifying antirheumatic drugs (DMARDs), but that hasn’t exactly translated to widespread practice.

While TDM has made some inroads with patients taking monoclonal antibodies, specifically infliximab, its uptake has encountered a number of headwinds, not the least of which is a lack of evidence and clinical guidelines, uneven access and standards of assays, and even an uncertainty about how to interpret laboratory results.

“In some fields, such as neurology, TDM is accepted for antiepileptics,” Michelle Petri, MD, MPH, director of the Johns Hopkins Lupus Center, Baltimore, told Medscape Medical News. “In rheumatology, though, TDM is underutilized and not adequately championed by the American College of Rheumatology.”

Johns Hopkins University

Duke University

Reactive vs Proactive TDM

Among the few trials that examined TDM in rheumatology patients are the NOR-DRUM A and B trials in Norway. Marthe Brun, MD, PhD, a rheumatologist at the Center for Treatment of Rheumatic and Musculoskeletal Diseases at Diakonhjemmet Hospital in Oslo, Norway, and a coauthor of the NOR-DRUM trials, told Medscape Medical News that the trials found an overall benefit to TDM during infliximab maintenance therapy. The trials included not only patients with inflammatory arthritis (rheumatoid arthritis, psoriatic arthritis, and spondyloarthritis) but also patients with inflammatory bowel disease and psoriasis, Brun said.

Nicolas Tourrenc

Brun explained that two types of TDM exist: Reactive and proactive. “Reactive TDM is when you use it to find the reason for a patient having a flare or disease worsening,” she told Medscape Medical News. “Proactive TDM would be regular testing to keep a patient within a therapeutic range to avoid flare because of low drug concentrations.”

Gastroenterologists are more inclined than rheumatologists and dermatologists to use reactive TDM, she said. “There have been no recommendations regarding proactive TDM because of the lack of data.”

In Europe, Wallace noted that European Alliance of Associations for Rheumatology (EULAR) recommendations consider the use of TDM in specific clinical scenarios, such as when treatment fails or to evaluate immunogenicity of a reaction, but they are limited. The American College of Rheumatology (ACR) does not have any recommendations for the use of TDM.

Based on the NOR-DRUM trials, rheumatologists in Norway have published their own guidelines for TDM for infliximab in rheumatologic disease, but they are in Norwegian and have not yet been taken up by EULAR, Brun noted. Publication of those recommendations in English is pending, she said.

“But for other subcutaneously administered TNF inhibitors, there’s a lack of data,” Brun added.
 

The State of the Evidence

NOR-DRUM A did not support the use of proactive TDM in the 30-week induction period as a way to improve disease remission in patients with chronic immune-mediated inflammatory disease. NOR-DRUM B, which evaluated TDM over a year, found the approach was more likely to lead to sustained disease control for that period.

Brun’s group recently published an analysis of the trials. “We did not find an overall effect during the initial phase of the treatment, the first 30 weeks,” she told Medscape Medical News.

“Then we looked at subgroups, and we found that the patients that developed antidrug antibodies [ADAs] had an effect, and ADA are associated with poorer outcomes as well as infusion reactions for patients treated with infliximab.

“So, it’s probably a benefit to be able to detect these ADA early before the patient experiences a disease flare or infusion reaction,” Brun added. “It facilitates for the clinician to take action to, for example, increase the dosing or switch therapy.”

However, the quality of the data supporting TDM in rheumatology is limited, Balevic said. “There’s very good observational data, but we have very few clinical trials that actually leverage TDM,” he said.

NOR-DRUM is the exception, he said. “Ideally, we need more of these dose-optimization trials to help guide clinical practice,” he said. But it stands alone.

Wallace noted several take-home messages from the NOR-DRUM trials, namely that using TDM to prevent ADA may be more effective during the maintenance phase of treatment than the induction phase. However, he said, the evidence is still emerging.

“It’s reasonable to say that we’re at an early stage of the evidence,” he said. “If you look at the large trials that have been done in rheumatology, they’ve combined patients with many different types of conditions, and a lot of our recommendations in rheumatology are disease-specific — in rheumatoid arthritis, in vasculitis. There’s a lack of data in specific diseases to guide or examine what the role of TDM might be.”

In the meantime, no fewer than four clinical trials evaluating TDM with tumor necrosis factor (TNF) inhibitors in rheumatologic diseases are ongoing or have completed but not yet released results, according to Wallace. Three Adalimumab Drug Optimization in Rheumatoid Arthritis trials are underway: The first is evaluating drug tapering vs disease activity score; the second is testing low or usual drug concentration; and the third is studying switches to etanercept or a non-TNF inhibitor drug (abatacept, rituximab, tocilizumab, or sarilumab) in patients failing treatment. Another trial called Tocilizumab Drug Levels to Optimized Treatment in RA is randomizing patients with high drug levels to dose maintenance or dose reduction. All four trials are sponsored by the Reade Rheumatology Research Institute, Amsterdam, the Netherlands.

Until clearer answers emerge from clinical trials, a number of barriers to and questions about the potential for TDM in rheumatology persist.
 

Barriers to Wider Use of TDM

“The biggest barrier with TDM is simply just a lack of what to do with the data,” Balevic said. “The clinician needs clear-cut guidance on what to do with the drug level. So, in other words, what is the target concentration for the drug? And if that target is not the goal, how should that dose be adjusted?”

The optimal drug levels, particularly for the older conventional synthetic DMARDs, simply have not been validated by clinical trials, he said.

“Different studies may report different target drug levels, and this could be due to different underlying population, or a different matrix — a measure of whole blood vs plasma — or even the timing of the sample,” he said. Balevic led a pharmacokinetic study earlier this year that proposed an algorithm for determining the number of missed hydroxychloroquine doses.

“This really goes back to the clinician needing to draw on a lot of pharmacology training to interpret the literature,” Balevic added.

That gets to the need for more education among rheumatologists, as Brun pointed out. “The physician needs to be educated about therapeutic ranges, when to assess concentrations of drug antibodies, and how to react to the results,” Brun said.

Which ADAs to identify is also problematic. “For antidrug antibodies, it’s especially challenging because there are so many assay formats in use, and it’s a bit complicated to analyze these antidrug antibodies,” Brun said. “There’s no consensus on what calibrators to use, and there’s no standardization of how to report the results, so you can’t really compare results from different assays. You need to know what your laboratory is using and how to interpret results from that particular assay, so that’s a challenge.”

Variability in drug tolerance also exists across assays, Wallace noted. “One of the challenges that have come up in the discussion of therapeutic drug monitoring is understanding what the target level is,” he said. “Defining what the target level might be for a specific condition is not something that’s well understood.”

Breaking down the science, he noted that an ADA can bind to a monoclonal antibody, forming an immune complex that avoids detection. Drug-sensitive assays may detect high concentrations of ADAs but miss low or moderate concentrations. Drug-tolerant assays may be more likely to detect low concentrations at ADAs, but the clinical significance is unclear.
 

Cost and Patient Trust as Barriers

“The costs vary a lot from assay to assay,” Brun said. “Some commercial assays can be really expensive.” In Norway, a dedicated lab with its own in-house assays helps to keep costs down, she said.

But that’s not the case in the United States, where insurance coverage can be a question mark, Shivani Garg, MD, a rheumatologist at the University of Wisconsin (UW)-Madison and director of the UW-Madison Health Lupus and Lupus Nephritis Clinics, told Medscape Medical News. “A lot of insurances are covering therapeutic drug monitoring, but for the high-deductible plans, there should be a way to offer these important tests to patients at a lower cost or figure out a way for coverage for those patients so that they can show that there are benefits of therapeutic drug monitoring without being sent a really big bill,” she said.

UW Health

Who May Benefit Most From TDM?

In the NOR-DRUM trials, patients at risk of developing ADA early on, before a disease flare or infusion reaction, seemed to benefit most from TDM. But who are those patients?

“We looked at risk factors for developing antidrug antibodies, and we found that patients with high disease activity when starting treatment, smokers, and patients with rheumatoid arthritis had a higher risk than other patients, as did patients who are not using concomitant immunosuppressive therapy,” Brun said.

“During treatment, we also found that low serum drug levels and drug holidays above 11 weeks were also risk factors,” she added.

The NOR-DRUM researchers also evaluated genetic risk factors and found that patients with the HLA-DQ2 gene variant were also at increased risk of developing ADA.

While NOR-DRUM evaluated only infliximab, some of its lessons may be applied to other DMARDs, Brun said. “We think that for other subcutaneously administered TNF inhibitors, you would probably see the same effect of proactive TDM, but we currently do not have data on that,” she said. A study similar to the NOR-DRUM design will evaluate this in Norway, Brun added.

She explained why the findings with infliximab may extend to adalimumab, which may be the second most immunogenic TNF inhibitor after infliximab. “The administration is different; it’s administered more often than infliximab; that would also make the results more uncertain to generalize to the other treatments, but I would guess there are also benefits of using TDM in other treatments.”
 

Potential Risks for TDM

Wallace has noted that TDM, with the current state of evidence, carries a number of potential risks. “The potential risks might be that you unnecessarily discontinue a medication because you detected an antibody, or the level seems low and you’re not able to get it higher, but the patient is otherwise doing fine,” he said. “You might end up increasing doses of the medicine that would put the patient at potentially increased risk of infection, as well as obviously more costs.”

That would also lead to more utilization of resources and costs, he said. “Some of those reasons are why there has been hesitation with therapeutic drug monitoring,” Wallace added.

A number of questions also surround the use of biosimilars and ADA levels, Wallace said. While a review of clinical trials found no meaningful differences in terms of immunogenicity between biosimilars and reference products, it did note discrepancies in how the agents were evaluated.
 

What DMARDs Are Most Suitable for TDM?

Petri said TDM would be useful for monitoring patients on mycophenolate mofetil. “A trough level can at least tell us if a patient is taking it,” she said. “Tacrolimus, used for lupus nephritis, has well-accepted peak and trough trends due to widespread use in transplant.”

Drugs with a wide variability in pharmacokinetics may also be suitable for TDM, Balevic said. That would include hydroxychloroquine, azathioprine, mycophenolate, or even cyclophosphamide. Drugs that have a narrow therapeutic index, such as tacrolimus, cyclosporine, or again, cyclophosphamide, might also be amenable to TDM, he said.
 

Why Do TDM?

“The two main reasons why somebody would go on to detect drug levels: The first may be to assess medication adherence, and this applies virtually to any drug that rheumatologists use; the second reason is to optimize dozing, either for efficacy purposes or to prevent toxicity,” Balevic said.

“When it comes to optimizing dosing, you should really think about TDM as one tool in our toolbelt,” he said.

Dose is “just a surrogate,” he said. “When we prescribe a drug, what truly matters is the amount of active unbound drug at the site of action. That’s what’s responsible for a drug’s pharmacologic effect.”

However, the same dose, or even the same weight-based dose, does not necessarily mean similar patients will achieve the same amount of exposure to the drug, but TDM can help determine that, he said.
 

What’s Next

Studies into the use of TDM in rheumatology are ongoing. Brun said her group is currently conducting a cost-effective analysis from the NOR-DRUM trials.

“There’s going to be more studies coming out in the next few years, looking at what impact the use of therapeutic drug monitoring might have on outcomes,” Wallace said.

“As we accumulate more and more evidence, we might see organizations like ACR and EULAR start to weigh in more on whether or not therapeutic drug monitoring can or should be used.”

Petri, Brun, and Garg had no relevant disclosures. Wallace disclosed financial relationships with Amgen, Alexion, BioCryst, Boehringer Ingelheim, Bristol Myers Squibb, Medpace, Novartis, Sanofi, Viela Bio, Visterra, Xencor, and Zenas. Balevic disclosed relationships with the National Institutes of Health, the Childhood Arthritis and Rheumatology Research Alliance, and UCB.
 

A version of this article appeared on Medscape.com.

Therapeutic drug monitoring (TDM) — the practice of using laboratory testing to measure blood levels of drugs — has garnered growing interest among rheumatologists in managing patients on disease-modifying antirheumatic drugs (DMARDs), but that hasn’t exactly translated to widespread practice.

While TDM has made some inroads with patients taking monoclonal antibodies, specifically infliximab, its uptake has encountered a number of headwinds, not the least of which is a lack of evidence and clinical guidelines, uneven access and standards of assays, and even an uncertainty about how to interpret laboratory results.

“In some fields, such as neurology, TDM is accepted for antiepileptics,” Michelle Petri, MD, MPH, director of the Johns Hopkins Lupus Center, Baltimore, told Medscape Medical News. “In rheumatology, though, TDM is underutilized and not adequately championed by the American College of Rheumatology.”

Johns Hopkins University

Duke University

Reactive vs Proactive TDM

Among the few trials that examined TDM in rheumatology patients are the NOR-DRUM A and B trials in Norway. Marthe Brun, MD, PhD, a rheumatologist at the Center for Treatment of Rheumatic and Musculoskeletal Diseases at Diakonhjemmet Hospital in Oslo, Norway, and a coauthor of the NOR-DRUM trials, told Medscape Medical News that the trials found an overall benefit to TDM during infliximab maintenance therapy. The trials included not only patients with inflammatory arthritis (rheumatoid arthritis, psoriatic arthritis, and spondyloarthritis) but also patients with inflammatory bowel disease and psoriasis, Brun said.

Nicolas Tourrenc

Brun explained that two types of TDM exist: Reactive and proactive. “Reactive TDM is when you use it to find the reason for a patient having a flare or disease worsening,” she told Medscape Medical News. “Proactive TDM would be regular testing to keep a patient within a therapeutic range to avoid flare because of low drug concentrations.”

Gastroenterologists are more inclined than rheumatologists and dermatologists to use reactive TDM, she said. “There have been no recommendations regarding proactive TDM because of the lack of data.”

In Europe, Wallace noted that European Alliance of Associations for Rheumatology (EULAR) recommendations consider the use of TDM in specific clinical scenarios, such as when treatment fails or to evaluate immunogenicity of a reaction, but they are limited. The American College of Rheumatology (ACR) does not have any recommendations for the use of TDM.

Based on the NOR-DRUM trials, rheumatologists in Norway have published their own guidelines for TDM for infliximab in rheumatologic disease, but they are in Norwegian and have not yet been taken up by EULAR, Brun noted. Publication of those recommendations in English is pending, she said.

“But for other subcutaneously administered TNF inhibitors, there’s a lack of data,” Brun added.
 

The State of the Evidence

NOR-DRUM A did not support the use of proactive TDM in the 30-week induction period as a way to improve disease remission in patients with chronic immune-mediated inflammatory disease. NOR-DRUM B, which evaluated TDM over a year, found the approach was more likely to lead to sustained disease control for that period.

Brun’s group recently published an analysis of the trials. “We did not find an overall effect during the initial phase of the treatment, the first 30 weeks,” she told Medscape Medical News.

“Then we looked at subgroups, and we found that the patients that developed antidrug antibodies [ADAs] had an effect, and ADA are associated with poorer outcomes as well as infusion reactions for patients treated with infliximab.

“So, it’s probably a benefit to be able to detect these ADA early before the patient experiences a disease flare or infusion reaction,” Brun added. “It facilitates for the clinician to take action to, for example, increase the dosing or switch therapy.”

However, the quality of the data supporting TDM in rheumatology is limited, Balevic said. “There’s very good observational data, but we have very few clinical trials that actually leverage TDM,” he said.

NOR-DRUM is the exception, he said. “Ideally, we need more of these dose-optimization trials to help guide clinical practice,” he said. But it stands alone.

Wallace noted several take-home messages from the NOR-DRUM trials, namely that using TDM to prevent ADA may be more effective during the maintenance phase of treatment than the induction phase. However, he said, the evidence is still emerging.

“It’s reasonable to say that we’re at an early stage of the evidence,” he said. “If you look at the large trials that have been done in rheumatology, they’ve combined patients with many different types of conditions, and a lot of our recommendations in rheumatology are disease-specific — in rheumatoid arthritis, in vasculitis. There’s a lack of data in specific diseases to guide or examine what the role of TDM might be.”

In the meantime, no fewer than four clinical trials evaluating TDM with tumor necrosis factor (TNF) inhibitors in rheumatologic diseases are ongoing or have completed but not yet released results, according to Wallace. Three Adalimumab Drug Optimization in Rheumatoid Arthritis trials are underway: The first is evaluating drug tapering vs disease activity score; the second is testing low or usual drug concentration; and the third is studying switches to etanercept or a non-TNF inhibitor drug (abatacept, rituximab, tocilizumab, or sarilumab) in patients failing treatment. Another trial called Tocilizumab Drug Levels to Optimized Treatment in RA is randomizing patients with high drug levels to dose maintenance or dose reduction. All four trials are sponsored by the Reade Rheumatology Research Institute, Amsterdam, the Netherlands.

Until clearer answers emerge from clinical trials, a number of barriers to and questions about the potential for TDM in rheumatology persist.
 

Barriers to Wider Use of TDM

“The biggest barrier with TDM is simply just a lack of what to do with the data,” Balevic said. “The clinician needs clear-cut guidance on what to do with the drug level. So, in other words, what is the target concentration for the drug? And if that target is not the goal, how should that dose be adjusted?”

The optimal drug levels, particularly for the older conventional synthetic DMARDs, simply have not been validated by clinical trials, he said.

“Different studies may report different target drug levels, and this could be due to different underlying population, or a different matrix — a measure of whole blood vs plasma — or even the timing of the sample,” he said. Balevic led a pharmacokinetic study earlier this year that proposed an algorithm for determining the number of missed hydroxychloroquine doses.

“This really goes back to the clinician needing to draw on a lot of pharmacology training to interpret the literature,” Balevic added.

That gets to the need for more education among rheumatologists, as Brun pointed out. “The physician needs to be educated about therapeutic ranges, when to assess concentrations of drug antibodies, and how to react to the results,” Brun said.

Which ADAs to identify is also problematic. “For antidrug antibodies, it’s especially challenging because there are so many assay formats in use, and it’s a bit complicated to analyze these antidrug antibodies,” Brun said. “There’s no consensus on what calibrators to use, and there’s no standardization of how to report the results, so you can’t really compare results from different assays. You need to know what your laboratory is using and how to interpret results from that particular assay, so that’s a challenge.”

Variability in drug tolerance also exists across assays, Wallace noted. “One of the challenges that have come up in the discussion of therapeutic drug monitoring is understanding what the target level is,” he said. “Defining what the target level might be for a specific condition is not something that’s well understood.”

Breaking down the science, he noted that an ADA can bind to a monoclonal antibody, forming an immune complex that avoids detection. Drug-sensitive assays may detect high concentrations of ADAs but miss low or moderate concentrations. Drug-tolerant assays may be more likely to detect low concentrations at ADAs, but the clinical significance is unclear.
 

Cost and Patient Trust as Barriers

“The costs vary a lot from assay to assay,” Brun said. “Some commercial assays can be really expensive.” In Norway, a dedicated lab with its own in-house assays helps to keep costs down, she said.

But that’s not the case in the United States, where insurance coverage can be a question mark, Shivani Garg, MD, a rheumatologist at the University of Wisconsin (UW)-Madison and director of the UW-Madison Health Lupus and Lupus Nephritis Clinics, told Medscape Medical News. “A lot of insurances are covering therapeutic drug monitoring, but for the high-deductible plans, there should be a way to offer these important tests to patients at a lower cost or figure out a way for coverage for those patients so that they can show that there are benefits of therapeutic drug monitoring without being sent a really big bill,” she said.

UW Health

Who May Benefit Most From TDM?

In the NOR-DRUM trials, patients at risk of developing ADA early on, before a disease flare or infusion reaction, seemed to benefit most from TDM. But who are those patients?

“We looked at risk factors for developing antidrug antibodies, and we found that patients with high disease activity when starting treatment, smokers, and patients with rheumatoid arthritis had a higher risk than other patients, as did patients who are not using concomitant immunosuppressive therapy,” Brun said.

“During treatment, we also found that low serum drug levels and drug holidays above 11 weeks were also risk factors,” she added.

The NOR-DRUM researchers also evaluated genetic risk factors and found that patients with the HLA-DQ2 gene variant were also at increased risk of developing ADA.

While NOR-DRUM evaluated only infliximab, some of its lessons may be applied to other DMARDs, Brun said. “We think that for other subcutaneously administered TNF inhibitors, you would probably see the same effect of proactive TDM, but we currently do not have data on that,” she said. A study similar to the NOR-DRUM design will evaluate this in Norway, Brun added.

She explained why the findings with infliximab may extend to adalimumab, which may be the second most immunogenic TNF inhibitor after infliximab. “The administration is different; it’s administered more often than infliximab; that would also make the results more uncertain to generalize to the other treatments, but I would guess there are also benefits of using TDM in other treatments.”
 

Potential Risks for TDM

Wallace has noted that TDM, with the current state of evidence, carries a number of potential risks. “The potential risks might be that you unnecessarily discontinue a medication because you detected an antibody, or the level seems low and you’re not able to get it higher, but the patient is otherwise doing fine,” he said. “You might end up increasing doses of the medicine that would put the patient at potentially increased risk of infection, as well as obviously more costs.”

That would also lead to more utilization of resources and costs, he said. “Some of those reasons are why there has been hesitation with therapeutic drug monitoring,” Wallace added.

A number of questions also surround the use of biosimilars and ADA levels, Wallace said. While a review of clinical trials found no meaningful differences in terms of immunogenicity between biosimilars and reference products, it did note discrepancies in how the agents were evaluated.
 

What DMARDs Are Most Suitable for TDM?

Petri said TDM would be useful for monitoring patients on mycophenolate mofetil. “A trough level can at least tell us if a patient is taking it,” she said. “Tacrolimus, used for lupus nephritis, has well-accepted peak and trough trends due to widespread use in transplant.”

Drugs with a wide variability in pharmacokinetics may also be suitable for TDM, Balevic said. That would include hydroxychloroquine, azathioprine, mycophenolate, or even cyclophosphamide. Drugs that have a narrow therapeutic index, such as tacrolimus, cyclosporine, or again, cyclophosphamide, might also be amenable to TDM, he said.
 

Why Do TDM?

“The two main reasons why somebody would go on to detect drug levels: The first may be to assess medication adherence, and this applies virtually to any drug that rheumatologists use; the second reason is to optimize dozing, either for efficacy purposes or to prevent toxicity,” Balevic said.

“When it comes to optimizing dosing, you should really think about TDM as one tool in our toolbelt,” he said.

Dose is “just a surrogate,” he said. “When we prescribe a drug, what truly matters is the amount of active unbound drug at the site of action. That’s what’s responsible for a drug’s pharmacologic effect.”

However, the same dose, or even the same weight-based dose, does not necessarily mean similar patients will achieve the same amount of exposure to the drug, but TDM can help determine that, he said.
 

What’s Next

Studies into the use of TDM in rheumatology are ongoing. Brun said her group is currently conducting a cost-effective analysis from the NOR-DRUM trials.

“There’s going to be more studies coming out in the next few years, looking at what impact the use of therapeutic drug monitoring might have on outcomes,” Wallace said.

“As we accumulate more and more evidence, we might see organizations like ACR and EULAR start to weigh in more on whether or not therapeutic drug monitoring can or should be used.”

Petri, Brun, and Garg had no relevant disclosures. Wallace disclosed financial relationships with Amgen, Alexion, BioCryst, Boehringer Ingelheim, Bristol Myers Squibb, Medpace, Novartis, Sanofi, Viela Bio, Visterra, Xencor, and Zenas. Balevic disclosed relationships with the National Institutes of Health, the Childhood Arthritis and Rheumatology Research Alliance, and UCB.
 

A version of this article appeared on Medscape.com.

Therapeutic drug monitoring (TDM) — the practice of using laboratory testing to measure blood levels of drugs — has garnered growing interest among rheumatologists in managing patients on disease-modifying antirheumatic drugs (DMARDs), but that hasn’t exactly translated to widespread practice.

While TDM has made some inroads with patients taking monoclonal antibodies, specifically infliximab, its uptake has encountered a number of headwinds, not the least of which is a lack of evidence and clinical guidelines, uneven access and standards of assays, and even an uncertainty about how to interpret laboratory results.

“In some fields, such as neurology, TDM is accepted for antiepileptics,” Michelle Petri, MD, MPH, director of the Johns Hopkins Lupus Center, Baltimore, told Medscape Medical News. “In rheumatology, though, TDM is underutilized and not adequately championed by the American College of Rheumatology.”

Johns Hopkins University

Duke University

Reactive vs Proactive TDM

Among the few trials that examined TDM in rheumatology patients are the NOR-DRUM A and B trials in Norway. Marthe Brun, MD, PhD, a rheumatologist at the Center for Treatment of Rheumatic and Musculoskeletal Diseases at Diakonhjemmet Hospital in Oslo, Norway, and a coauthor of the NOR-DRUM trials, told Medscape Medical News that the trials found an overall benefit to TDM during infliximab maintenance therapy. The trials included not only patients with inflammatory arthritis (rheumatoid arthritis, psoriatic arthritis, and spondyloarthritis) but also patients with inflammatory bowel disease and psoriasis, Brun said.

Nicolas Tourrenc

Brun explained that two types of TDM exist: Reactive and proactive. “Reactive TDM is when you use it to find the reason for a patient having a flare or disease worsening,” she told Medscape Medical News. “Proactive TDM would be regular testing to keep a patient within a therapeutic range to avoid flare because of low drug concentrations.”

Gastroenterologists are more inclined than rheumatologists and dermatologists to use reactive TDM, she said. “There have been no recommendations regarding proactive TDM because of the lack of data.”

In Europe, Wallace noted that European Alliance of Associations for Rheumatology (EULAR) recommendations consider the use of TDM in specific clinical scenarios, such as when treatment fails or to evaluate immunogenicity of a reaction, but they are limited. The American College of Rheumatology (ACR) does not have any recommendations for the use of TDM.

Based on the NOR-DRUM trials, rheumatologists in Norway have published their own guidelines for TDM for infliximab in rheumatologic disease, but they are in Norwegian and have not yet been taken up by EULAR, Brun noted. Publication of those recommendations in English is pending, she said.

“But for other subcutaneously administered TNF inhibitors, there’s a lack of data,” Brun added.
 

The State of the Evidence

NOR-DRUM A did not support the use of proactive TDM in the 30-week induction period as a way to improve disease remission in patients with chronic immune-mediated inflammatory disease. NOR-DRUM B, which evaluated TDM over a year, found the approach was more likely to lead to sustained disease control for that period.

Brun’s group recently published an analysis of the trials. “We did not find an overall effect during the initial phase of the treatment, the first 30 weeks,” she told Medscape Medical News.

“Then we looked at subgroups, and we found that the patients that developed antidrug antibodies [ADAs] had an effect, and ADA are associated with poorer outcomes as well as infusion reactions for patients treated with infliximab.

“So, it’s probably a benefit to be able to detect these ADA early before the patient experiences a disease flare or infusion reaction,” Brun added. “It facilitates for the clinician to take action to, for example, increase the dosing or switch therapy.”

However, the quality of the data supporting TDM in rheumatology is limited, Balevic said. “There’s very good observational data, but we have very few clinical trials that actually leverage TDM,” he said.

NOR-DRUM is the exception, he said. “Ideally, we need more of these dose-optimization trials to help guide clinical practice,” he said. But it stands alone.

Wallace noted several take-home messages from the NOR-DRUM trials, namely that using TDM to prevent ADA may be more effective during the maintenance phase of treatment than the induction phase. However, he said, the evidence is still emerging.

“It’s reasonable to say that we’re at an early stage of the evidence,” he said. “If you look at the large trials that have been done in rheumatology, they’ve combined patients with many different types of conditions, and a lot of our recommendations in rheumatology are disease-specific — in rheumatoid arthritis, in vasculitis. There’s a lack of data in specific diseases to guide or examine what the role of TDM might be.”

In the meantime, no fewer than four clinical trials evaluating TDM with tumor necrosis factor (TNF) inhibitors in rheumatologic diseases are ongoing or have completed but not yet released results, according to Wallace. Three Adalimumab Drug Optimization in Rheumatoid Arthritis trials are underway: The first is evaluating drug tapering vs disease activity score; the second is testing low or usual drug concentration; and the third is studying switches to etanercept or a non-TNF inhibitor drug (abatacept, rituximab, tocilizumab, or sarilumab) in patients failing treatment. Another trial called Tocilizumab Drug Levels to Optimized Treatment in RA is randomizing patients with high drug levels to dose maintenance or dose reduction. All four trials are sponsored by the Reade Rheumatology Research Institute, Amsterdam, the Netherlands.

Until clearer answers emerge from clinical trials, a number of barriers to and questions about the potential for TDM in rheumatology persist.
 

Barriers to Wider Use of TDM

“The biggest barrier with TDM is simply just a lack of what to do with the data,” Balevic said. “The clinician needs clear-cut guidance on what to do with the drug level. So, in other words, what is the target concentration for the drug? And if that target is not the goal, how should that dose be adjusted?”

The optimal drug levels, particularly for the older conventional synthetic DMARDs, simply have not been validated by clinical trials, he said.

“Different studies may report different target drug levels, and this could be due to different underlying population, or a different matrix — a measure of whole blood vs plasma — or even the timing of the sample,” he said. Balevic led a pharmacokinetic study earlier this year that proposed an algorithm for determining the number of missed hydroxychloroquine doses.

“This really goes back to the clinician needing to draw on a lot of pharmacology training to interpret the literature,” Balevic added.

That gets to the need for more education among rheumatologists, as Brun pointed out. “The physician needs to be educated about therapeutic ranges, when to assess concentrations of drug antibodies, and how to react to the results,” Brun said.

Which ADAs to identify is also problematic. “For antidrug antibodies, it’s especially challenging because there are so many assay formats in use, and it’s a bit complicated to analyze these antidrug antibodies,” Brun said. “There’s no consensus on what calibrators to use, and there’s no standardization of how to report the results, so you can’t really compare results from different assays. You need to know what your laboratory is using and how to interpret results from that particular assay, so that’s a challenge.”

Variability in drug tolerance also exists across assays, Wallace noted. “One of the challenges that have come up in the discussion of therapeutic drug monitoring is understanding what the target level is,” he said. “Defining what the target level might be for a specific condition is not something that’s well understood.”

Breaking down the science, he noted that an ADA can bind to a monoclonal antibody, forming an immune complex that avoids detection. Drug-sensitive assays may detect high concentrations of ADAs but miss low or moderate concentrations. Drug-tolerant assays may be more likely to detect low concentrations at ADAs, but the clinical significance is unclear.
 

Cost and Patient Trust as Barriers

“The costs vary a lot from assay to assay,” Brun said. “Some commercial assays can be really expensive.” In Norway, a dedicated lab with its own in-house assays helps to keep costs down, she said.

But that’s not the case in the United States, where insurance coverage can be a question mark, Shivani Garg, MD, a rheumatologist at the University of Wisconsin (UW)-Madison and director of the UW-Madison Health Lupus and Lupus Nephritis Clinics, told Medscape Medical News. “A lot of insurances are covering therapeutic drug monitoring, but for the high-deductible plans, there should be a way to offer these important tests to patients at a lower cost or figure out a way for coverage for those patients so that they can show that there are benefits of therapeutic drug monitoring without being sent a really big bill,” she said.

UW Health

Who May Benefit Most From TDM?

In the NOR-DRUM trials, patients at risk of developing ADA early on, before a disease flare or infusion reaction, seemed to benefit most from TDM. But who are those patients?

“We looked at risk factors for developing antidrug antibodies, and we found that patients with high disease activity when starting treatment, smokers, and patients with rheumatoid arthritis had a higher risk than other patients, as did patients who are not using concomitant immunosuppressive therapy,” Brun said.

“During treatment, we also found that low serum drug levels and drug holidays above 11 weeks were also risk factors,” she added.

The NOR-DRUM researchers also evaluated genetic risk factors and found that patients with the HLA-DQ2 gene variant were also at increased risk of developing ADA.

While NOR-DRUM evaluated only infliximab, some of its lessons may be applied to other DMARDs, Brun said. “We think that for other subcutaneously administered TNF inhibitors, you would probably see the same effect of proactive TDM, but we currently do not have data on that,” she said. A study similar to the NOR-DRUM design will evaluate this in Norway, Brun added.

She explained why the findings with infliximab may extend to adalimumab, which may be the second most immunogenic TNF inhibitor after infliximab. “The administration is different; it’s administered more often than infliximab; that would also make the results more uncertain to generalize to the other treatments, but I would guess there are also benefits of using TDM in other treatments.”
 

Potential Risks for TDM

Wallace has noted that TDM, with the current state of evidence, carries a number of potential risks. “The potential risks might be that you unnecessarily discontinue a medication because you detected an antibody, or the level seems low and you’re not able to get it higher, but the patient is otherwise doing fine,” he said. “You might end up increasing doses of the medicine that would put the patient at potentially increased risk of infection, as well as obviously more costs.”

That would also lead to more utilization of resources and costs, he said. “Some of those reasons are why there has been hesitation with therapeutic drug monitoring,” Wallace added.

A number of questions also surround the use of biosimilars and ADA levels, Wallace said. While a review of clinical trials found no meaningful differences in terms of immunogenicity between biosimilars and reference products, it did note discrepancies in how the agents were evaluated.
 

What DMARDs Are Most Suitable for TDM?

Petri said TDM would be useful for monitoring patients on mycophenolate mofetil. “A trough level can at least tell us if a patient is taking it,” she said. “Tacrolimus, used for lupus nephritis, has well-accepted peak and trough trends due to widespread use in transplant.”

Drugs with a wide variability in pharmacokinetics may also be suitable for TDM, Balevic said. That would include hydroxychloroquine, azathioprine, mycophenolate, or even cyclophosphamide. Drugs that have a narrow therapeutic index, such as tacrolimus, cyclosporine, or again, cyclophosphamide, might also be amenable to TDM, he said.
 

Why Do TDM?

“The two main reasons why somebody would go on to detect drug levels: The first may be to assess medication adherence, and this applies virtually to any drug that rheumatologists use; the second reason is to optimize dozing, either for efficacy purposes or to prevent toxicity,” Balevic said.

“When it comes to optimizing dosing, you should really think about TDM as one tool in our toolbelt,” he said.

Dose is “just a surrogate,” he said. “When we prescribe a drug, what truly matters is the amount of active unbound drug at the site of action. That’s what’s responsible for a drug’s pharmacologic effect.”

However, the same dose, or even the same weight-based dose, does not necessarily mean similar patients will achieve the same amount of exposure to the drug, but TDM can help determine that, he said.
 

What’s Next

Studies into the use of TDM in rheumatology are ongoing. Brun said her group is currently conducting a cost-effective analysis from the NOR-DRUM trials.

“There’s going to be more studies coming out in the next few years, looking at what impact the use of therapeutic drug monitoring might have on outcomes,” Wallace said.

“As we accumulate more and more evidence, we might see organizations like ACR and EULAR start to weigh in more on whether or not therapeutic drug monitoring can or should be used.”

Petri, Brun, and Garg had no relevant disclosures. Wallace disclosed financial relationships with Amgen, Alexion, BioCryst, Boehringer Ingelheim, Bristol Myers Squibb, Medpace, Novartis, Sanofi, Viela Bio, Visterra, Xencor, and Zenas. Balevic disclosed relationships with the National Institutes of Health, the Childhood Arthritis and Rheumatology Research Alliance, and UCB.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Patients with systemic sclerosis (SSc) who exhibit abnormal small bowel transit are more likely to be men, experience more severe cardiac involvement, have a higher mortality risk, and show fewer sicca symptoms.

METHODOLOGY:

• Researchers enrolled 130 patients with SSc having gastrointestinal (GI) symptoms (mean age at symptom onset, 56.8 years; 90% women; 81% White) seen at the Johns Hopkins Scleroderma Center, Baltimore, from October 2014 to May 2022.
• Clinical data and serum samples were longitudinally collected from all actively followed patients at the time of enrollment and every 6 months thereafter (median disease duration, 8.4 years).
• Participants underwent whole gut transit scintigraphy for the assessment of small bowel motility.
• A cross-sectional analysis compared the clinical features of patients with (n = 22; mean age at symptom onset, 61.4 years) and without (n = 108; mean age at symptom onset, 55.8 years) abnormal small bowel transit.

TAKEAWAY:

• Men with SSc (odds ratio [OR], 3.70; P = .038) and those with severe cardiac involvement (OR, 3.98; P = .035) were more likely to have abnormal small bowel transit.
• Sicca symptoms were negatively associated with abnormal small bowel transit in patients with SSc (adjusted OR, 0.28; P = .043).
• Patients with abnormal small bowel transit reported significantly worse  (P = .028) and social functioning (P = .015) than those having a normal transit.
• A multivariate analysis showed that patients with abnormal small bowel transit had higher mortality than those with a normal transit (adjusted hazard ratio, 5.03; P = .005).

IN PRACTICE:

“Our findings improve our understanding of risk factors associated with abnormal small bowel transit in SSc patients and shed light on the lived experience of patients with this GI [gastrointestinal] complication,” the authors wrote. “Overall, these findings are important for patient risk stratification and monitoring and will help to identify a more homogeneous group of patients for future clinical and translational studies,” they added.

SOURCE:

The study was led by Jenice X. Cheah, MD, University of California, Los Angeles. It was published online on October 7, 2024, in Rheumatology.

LIMITATIONS:

The study may be subject to referral bias as it was conducted at a tertiary referral center, potentially including patients with a more severe disease status. Furthermore, this study was retrospective in nature, and whole gut transit studies were not conducted in all the patients seen at the referral center. Additionally, the cross-sectional design limited the ability to establish causality between the clinical features and abnormal small bowel transit.

DISCLOSURES:

The study was supported by grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. The authors declared no conflicts of interest.
 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Patients with systemic sclerosis (SSc) who exhibit abnormal small bowel transit are more likely to be men, experience more severe cardiac involvement, have a higher mortality risk, and show fewer sicca symptoms.

METHODOLOGY:

• Researchers enrolled 130 patients with SSc having gastrointestinal (GI) symptoms (mean age at symptom onset, 56.8 years; 90% women; 81% White) seen at the Johns Hopkins Scleroderma Center, Baltimore, from October 2014 to May 2022.
• Clinical data and serum samples were longitudinally collected from all actively followed patients at the time of enrollment and every 6 months thereafter (median disease duration, 8.4 years).
• Participants underwent whole gut transit scintigraphy for the assessment of small bowel motility.
• A cross-sectional analysis compared the clinical features of patients with (n = 22; mean age at symptom onset, 61.4 years) and without (n = 108; mean age at symptom onset, 55.8 years) abnormal small bowel transit.

TAKEAWAY:

• Men with SSc (odds ratio [OR], 3.70; P = .038) and those with severe cardiac involvement (OR, 3.98; P = .035) were more likely to have abnormal small bowel transit.
• Sicca symptoms were negatively associated with abnormal small bowel transit in patients with SSc (adjusted OR, 0.28; P = .043).
• Patients with abnormal small bowel transit reported significantly worse  (P = .028) and social functioning (P = .015) than those having a normal transit.
• A multivariate analysis showed that patients with abnormal small bowel transit had higher mortality than those with a normal transit (adjusted hazard ratio, 5.03; P = .005).

IN PRACTICE:

“Our findings improve our understanding of risk factors associated with abnormal small bowel transit in SSc patients and shed light on the lived experience of patients with this GI [gastrointestinal] complication,” the authors wrote. “Overall, these findings are important for patient risk stratification and monitoring and will help to identify a more homogeneous group of patients for future clinical and translational studies,” they added.

SOURCE:

The study was led by Jenice X. Cheah, MD, University of California, Los Angeles. It was published online on October 7, 2024, in Rheumatology.

LIMITATIONS:

The study may be subject to referral bias as it was conducted at a tertiary referral center, potentially including patients with a more severe disease status. Furthermore, this study was retrospective in nature, and whole gut transit studies were not conducted in all the patients seen at the referral center. Additionally, the cross-sectional design limited the ability to establish causality between the clinical features and abnormal small bowel transit.

DISCLOSURES:

The study was supported by grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. The authors declared no conflicts of interest.
 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Patients with systemic sclerosis (SSc) who exhibit abnormal small bowel transit are more likely to be men, experience more severe cardiac involvement, have a higher mortality risk, and show fewer sicca symptoms.

METHODOLOGY:

• Researchers enrolled 130 patients with SSc having gastrointestinal (GI) symptoms (mean age at symptom onset, 56.8 years; 90% women; 81% White) seen at the Johns Hopkins Scleroderma Center, Baltimore, from October 2014 to May 2022.
• Clinical data and serum samples were longitudinally collected from all actively followed patients at the time of enrollment and every 6 months thereafter (median disease duration, 8.4 years).
• Participants underwent whole gut transit scintigraphy for the assessment of small bowel motility.
• A cross-sectional analysis compared the clinical features of patients with (n = 22; mean age at symptom onset, 61.4 years) and without (n = 108; mean age at symptom onset, 55.8 years) abnormal small bowel transit.

TAKEAWAY:

• Men with SSc (odds ratio [OR], 3.70; P = .038) and those with severe cardiac involvement (OR, 3.98; P = .035) were more likely to have abnormal small bowel transit.
• Sicca symptoms were negatively associated with abnormal small bowel transit in patients with SSc (adjusted OR, 0.28; P = .043).
• Patients with abnormal small bowel transit reported significantly worse  (P = .028) and social functioning (P = .015) than those having a normal transit.
• A multivariate analysis showed that patients with abnormal small bowel transit had higher mortality than those with a normal transit (adjusted hazard ratio, 5.03; P = .005).

IN PRACTICE:

“Our findings improve our understanding of risk factors associated with abnormal small bowel transit in SSc patients and shed light on the lived experience of patients with this GI [gastrointestinal] complication,” the authors wrote. “Overall, these findings are important for patient risk stratification and monitoring and will help to identify a more homogeneous group of patients for future clinical and translational studies,” they added.

SOURCE:

The study was led by Jenice X. Cheah, MD, University of California, Los Angeles. It was published online on October 7, 2024, in Rheumatology.

LIMITATIONS:

The study may be subject to referral bias as it was conducted at a tertiary referral center, potentially including patients with a more severe disease status. Furthermore, this study was retrospective in nature, and whole gut transit studies were not conducted in all the patients seen at the referral center. Additionally, the cross-sectional design limited the ability to establish causality between the clinical features and abnormal small bowel transit.

DISCLOSURES:

The study was supported by grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. The authors declared no conflicts of interest.
 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Depending on one’s perspective, “mast cell activation syndrome (MCAS)” is either a relatively rare, narrowly defined severe allergic condition or a vastly underrecognized underlying cause of multiple chronic inflammatory conditions that affect roughly 17% of the entire population. 

Inappropriate activation of mast cells — now termed mast cell activation disease (MCAD) — has long been known to underlie allergic symptoms and inflammation, and far less commonly, neoplasias such as mastocytosis. The concept of chronic, persistent MCAS associated with aberrant growth and dystrophism is more recent, emerging only in the last couple of decades as a separate entity under the MCAD heading. 

Observational studies and clinical experience have linked signs and symptoms of MCAS with other inflammatory chronic conditions such as hypermobile Ehlers-Danlos Syndrome (EDS), postural orthostatic tachycardia syndrome (POTS), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and recently, long COVID. However, those conditions themselves are diagnostically challenging, and as yet there is no proof of causation.

The idea that MCAS is the entity — or at least, a key one — at the center of “a confoundingly, extraordinarily heterogeneous chronic multisystem polymorbidity” was the theme of a recent 4-day meeting of a professional group informally dubbed “Masterminds.” Since their first meeting in 2018, the group has grown from about 35 to nearly 650 multidisciplinary professionals. 

Stephanie L. Grach, MD, assistant professor of medicine at the Mayo Clinic, Rochester, Minnesota, gave an introductory talk about the importance of changing “the medical paradigm around complex chronic illness.” Much of the rest of the meeting was devoted to sharing approaches for managing MCAS comorbidities, including dysautonomia, hypermobility, and associated craniocervical dysfunction, and various other multi-system conditions characterized by chronic pain and/or fatigue. Several talks covered the use of agents that block mast cell activity as potential treatment. 

In an interview, Grach said “the meeting was an exciting example of how not only research, but also medicine, is moving forward, and it’s really cool to see that people are independently coming to very similar conclusions about shared pathologies, and because of that, the importance of overlap amongst complex medical conditions that historically have really been poorly addressed.”

She added, “mast cell activation, or mast cell hyperactivity, is one part of the greater picture. What’s important about the mast cell component is that of the multiple different targetable pathologies, it’s one that currently has potential available therapies that can be explored, some of them relatively easily.”

But Christopher Chang, MD, PhD, chief of the Pediatric Allergy and Immunology program, Joe DiMaggio Children’s Hospital, Hollywood, Florida, sees it differently. In an interview, he noted that the reason for disagreement over what constitutes MCAS is that “it doesn’t have a lot of objective findings that we can identify. ... We know that mast cells are important immune cells, just like all immune cells are important. It seems like whenever someone has unexplained symptoms, people try to blame it on mast cells. But it’s very hard to prove that.” 
 

Two Definitions Characterize the Illness Differently

One proposed “consensus” MCAS definition was first published in 2011 by a group led by hematologist Peter Valent, MD, of the Medical University of Vienna in Austria. It has been revised since, and similar versions adopted by medical societies, including the American Academy of Allergy, Asthma & Immunology (AAAAI). The most recent versions propose three core MCAS criteria: 

• Typical clinical signs of severe, recurrent (episodic) systemic (at least two organ systems) MCA are present (often in the form of anaphylaxis).
• The involvement of mast cells (MCs) is documented by biochemical studies, preferably an increase in serum tryptase levels from the individual’s baseline to plus 20% + 2 ng/mL.
• Response of symptoms to therapy with MC-stabilizing agents, drugs directed against MC mediator production, or drugs blocking mediator release or effects of MC-derived mediators.

The following year, a separate publication authored by Gerhard J. Molderings, MD, University of Bonn in Germany, and colleagues proposed a much broader MCAS definition. Also revised since, the latest “consensus-2” was published in 2020. This definition consists of one major criterion: “A constellation of clinical complaints attributable to pathologically increased MC activity, ie, MC mediator release syndrome.” This “constellation” involves conditions of nearly every organ system that, taken together, are estimated to affect up to 17% of the entire population. These are just a few examples: 

• Constitutional: Chronic fatigue, flushing, or sweats
• Dermatologic: Rashes or lesions
• Ophthalmologic: dry eyes
• Oral: Burning or itching in mouth
• Pulmonary: Airway inflammation at any/all levels
• Cardiovascular: Blood pressure lability or codiagnosis of POTS is common
• Gastrointestinal: Reflux, dysphagia, or malabsorption
• Genitourinary: Endometriosis, dysmenorrhea, or dyspareunia
• Musculoskeletal/connective tissue: Fibromyalgia or diagnosis of hypermobile EDS is common
• Neurologic: Headaches or sensory neuropathies
• Psychiatric: Depression or anxiety
• Endocrinologic: Thyroid disease or dyslipidemia
• Hematologic: Polycythemia or anemia (after ruling out other causes)

The diagnosis is made by fulfilling that major criterion, plus at least one objective assessment of pathologically increased release of MC mediators, including infiltrates, abnormal MC morphology, or MC genetic changes shown to increase MC activity. Other alternatives include evidence of above-normal levels of MC mediators, including tryptase, histamine or its metabolites, heparin, or chromatin A, in whole blood, serum, plasma, or urine. Symptomatic response to MC activation inhibitors can also be used but isn’t required as it is in the other definition. 
 

Underdiagnosis vs Overdiagnosis

Lawrence B. Afrin, MD, senior consultant in hematology/oncology at the AIM Center for Personalized Medicine, Westchester, New York, and lead author of the 2020 update of the broader “consensus-2” criteria, said in an interview, “we now know MCAS exists, and it’s prevalent, even though, for understandable and forgivable reasons, we’ve been missing it all along. ... If you see a patient who has this chronic, multisystem unwellness with general themes of inflammation plus or minus allergic issues and you can’t find some other rational explanation that better accounts for what’s going on ... then it’s reasonable to think to include MCAS in the differential diagnosis. If the patient happens not to fit the diagnostic criteria being advanced by one group, that doesn’t necessarily rule out the possibility that this is still going on.”

Afrin, along with his coauthors, faulted the narrower “consensus-1” definition for lacking data to support the “20% + 2” criteria for requiring the difficult determination of a patient’s “baseline” and for requiring evidence of response to treatment prior to making the diagnosis. Not all patients will respond to a given histamine blocker, he noted. 

But Lawrence B. Schwartz, MD, PhD, an author on both the Valent and AAAAI criteria, disagreed, noting that the narrower criteria “appear to have a high degree of specificity and sensitivity when the reaction is systemic and involves hypotension. Less severe clinical events, particularly involving the gastrointestinal or central nervous systems, do not have precise clinical or biomarker criteria for identifying mast cell involvement.” 

Added Schwartz, who is professor of medicine and chair of the Division of Rheumatology, Allergy, and Immunology and program director of Allergy and Immunology, Virginia Commonwealth University (VCU), Richmond, “when mast cell activation events occur only in the skin, we refer to it as chronic urticaria and in the airways or conjunctiva of allergic individuals as allergic asthma, rhinitis, and/or conjunctivitis. The absence of specific criteria for mast cell activation in the GI [gastrointestinal] tract or CNS [central nervous system] neither rules in mast cell involvement nor does it rule out mast cell involvement. Thus, more research is needed to find better diagnostic criteria.”

Schwartz also pointed to a recent paper reporting the use of artificial intelligence models to “quantify diagnostic precision and specificity” of “alternative” MCAS definitions. The conclusion was a “lack of specificity is pronounced in relation to multiple control criteria, raising the concern that alternative criteria could disproportionately contribute to MCAS overdiagnosis, to the exclusion of more appropriate diagnoses.”

During the meeting, Afrin acknowledged that the broader view risks overdiagnosis of MCAS. However, he also referenced Occam’s razor, the principle that the simplest explanation is probably the best one. “Which scenario is more likely? Multiple diagnoses and problems that are all independent of each other vs one diagnosis that’s biologically capable of causing most or all of the findings, ie, the simplest solution even if it’s not the most immediately obvious solution?”

He said in an interview: “Do we have any proof that MCAS is what’s underlying hypermobile Ehlers-Danlos or POTS or chronic fatigue? No, we don’t have any proof, not because anybody has done studies that have shown there to be no connection but simply because we’re so early in our awareness that the disease even exists that the necessary studies haven’t even been done yet.”

At the meeting, Afrin introduced proposals to turn the “Masterminds” group into a formal professional society and to launch a journal. He also gave an update on progress in developing a symptom assessment tool both for clinical use and to enable clinical trials of new drugs to target mast cells or their mediators. The plan is to field test the tool in 2025 and publish those results in 2026. 

Grach, Afrin, and Chang had no disclosures. Schwartz discovered tryptase and invented the Thermo Fisher tryptase assay, for which his institution (VCU) receives royalties that are shared with him. He also invented monoclonal antibodies used for detecting mast cells or basophils, for which VCU receives royalties from several companies, including Millipore, Santa Cruz, BioLegend, and Hycult Biotech, that are also shared with him. He is a paid consultant for Blueprint Medicines, Celldex Therapeutics, Invea, Third Harmonic Bio, HYCOR Biomedical, Jasper, TerSera Therapeutics, and GLG. He also serves on an AstraZeneca data safety monitoring board for a clinical trial involving benralizumab treatment of hypereosinophilic syndrome and receives royalties from UpToDate (biomarkers for anaphylaxis) and Goldman-Cecil Medicine (anaphylaxis).

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

Depending on one’s perspective, “mast cell activation syndrome (MCAS)” is either a relatively rare, narrowly defined severe allergic condition or a vastly underrecognized underlying cause of multiple chronic inflammatory conditions that affect roughly 17% of the entire population. 

Inappropriate activation of mast cells — now termed mast cell activation disease (MCAD) — has long been known to underlie allergic symptoms and inflammation, and far less commonly, neoplasias such as mastocytosis. The concept of chronic, persistent MCAS associated with aberrant growth and dystrophism is more recent, emerging only in the last couple of decades as a separate entity under the MCAD heading. 

Observational studies and clinical experience have linked signs and symptoms of MCAS with other inflammatory chronic conditions such as hypermobile Ehlers-Danlos Syndrome (EDS), postural orthostatic tachycardia syndrome (POTS), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and recently, long COVID. However, those conditions themselves are diagnostically challenging, and as yet there is no proof of causation.

The idea that MCAS is the entity — or at least, a key one — at the center of “a confoundingly, extraordinarily heterogeneous chronic multisystem polymorbidity” was the theme of a recent 4-day meeting of a professional group informally dubbed “Masterminds.” Since their first meeting in 2018, the group has grown from about 35 to nearly 650 multidisciplinary professionals. 

Stephanie L. Grach, MD, assistant professor of medicine at the Mayo Clinic, Rochester, Minnesota, gave an introductory talk about the importance of changing “the medical paradigm around complex chronic illness.” Much of the rest of the meeting was devoted to sharing approaches for managing MCAS comorbidities, including dysautonomia, hypermobility, and associated craniocervical dysfunction, and various other multi-system conditions characterized by chronic pain and/or fatigue. Several talks covered the use of agents that block mast cell activity as potential treatment. 

In an interview, Grach said “the meeting was an exciting example of how not only research, but also medicine, is moving forward, and it’s really cool to see that people are independently coming to very similar conclusions about shared pathologies, and because of that, the importance of overlap amongst complex medical conditions that historically have really been poorly addressed.”

She added, “mast cell activation, or mast cell hyperactivity, is one part of the greater picture. What’s important about the mast cell component is that of the multiple different targetable pathologies, it’s one that currently has potential available therapies that can be explored, some of them relatively easily.”

But Christopher Chang, MD, PhD, chief of the Pediatric Allergy and Immunology program, Joe DiMaggio Children’s Hospital, Hollywood, Florida, sees it differently. In an interview, he noted that the reason for disagreement over what constitutes MCAS is that “it doesn’t have a lot of objective findings that we can identify. ... We know that mast cells are important immune cells, just like all immune cells are important. It seems like whenever someone has unexplained symptoms, people try to blame it on mast cells. But it’s very hard to prove that.” 
 

Two Definitions Characterize the Illness Differently

One proposed “consensus” MCAS definition was first published in 2011 by a group led by hematologist Peter Valent, MD, of the Medical University of Vienna in Austria. It has been revised since, and similar versions adopted by medical societies, including the American Academy of Allergy, Asthma & Immunology (AAAAI). The most recent versions propose three core MCAS criteria: 

• Typical clinical signs of severe, recurrent (episodic) systemic (at least two organ systems) MCA are present (often in the form of anaphylaxis).
• The involvement of mast cells (MCs) is documented by biochemical studies, preferably an increase in serum tryptase levels from the individual’s baseline to plus 20% + 2 ng/mL.
• Response of symptoms to therapy with MC-stabilizing agents, drugs directed against MC mediator production, or drugs blocking mediator release or effects of MC-derived mediators.

The following year, a separate publication authored by Gerhard J. Molderings, MD, University of Bonn in Germany, and colleagues proposed a much broader MCAS definition. Also revised since, the latest “consensus-2” was published in 2020. This definition consists of one major criterion: “A constellation of clinical complaints attributable to pathologically increased MC activity, ie, MC mediator release syndrome.” This “constellation” involves conditions of nearly every organ system that, taken together, are estimated to affect up to 17% of the entire population. These are just a few examples: 

• Constitutional: Chronic fatigue, flushing, or sweats
• Dermatologic: Rashes or lesions
• Ophthalmologic: dry eyes
• Oral: Burning or itching in mouth
• Pulmonary: Airway inflammation at any/all levels
• Cardiovascular: Blood pressure lability or codiagnosis of POTS is common
• Gastrointestinal: Reflux, dysphagia, or malabsorption
• Genitourinary: Endometriosis, dysmenorrhea, or dyspareunia
• Musculoskeletal/connective tissue: Fibromyalgia or diagnosis of hypermobile EDS is common
• Neurologic: Headaches or sensory neuropathies
• Psychiatric: Depression or anxiety
• Endocrinologic: Thyroid disease or dyslipidemia
• Hematologic: Polycythemia or anemia (after ruling out other causes)

The diagnosis is made by fulfilling that major criterion, plus at least one objective assessment of pathologically increased release of MC mediators, including infiltrates, abnormal MC morphology, or MC genetic changes shown to increase MC activity. Other alternatives include evidence of above-normal levels of MC mediators, including tryptase, histamine or its metabolites, heparin, or chromatin A, in whole blood, serum, plasma, or urine. Symptomatic response to MC activation inhibitors can also be used but isn’t required as it is in the other definition. 
 

Underdiagnosis vs Overdiagnosis

Lawrence B. Afrin, MD, senior consultant in hematology/oncology at the AIM Center for Personalized Medicine, Westchester, New York, and lead author of the 2020 update of the broader “consensus-2” criteria, said in an interview, “we now know MCAS exists, and it’s prevalent, even though, for understandable and forgivable reasons, we’ve been missing it all along. ... If you see a patient who has this chronic, multisystem unwellness with general themes of inflammation plus or minus allergic issues and you can’t find some other rational explanation that better accounts for what’s going on ... then it’s reasonable to think to include MCAS in the differential diagnosis. If the patient happens not to fit the diagnostic criteria being advanced by one group, that doesn’t necessarily rule out the possibility that this is still going on.”

Afrin, along with his coauthors, faulted the narrower “consensus-1” definition for lacking data to support the “20% + 2” criteria for requiring the difficult determination of a patient’s “baseline” and for requiring evidence of response to treatment prior to making the diagnosis. Not all patients will respond to a given histamine blocker, he noted. 

But Lawrence B. Schwartz, MD, PhD, an author on both the Valent and AAAAI criteria, disagreed, noting that the narrower criteria “appear to have a high degree of specificity and sensitivity when the reaction is systemic and involves hypotension. Less severe clinical events, particularly involving the gastrointestinal or central nervous systems, do not have precise clinical or biomarker criteria for identifying mast cell involvement.” 

Added Schwartz, who is professor of medicine and chair of the Division of Rheumatology, Allergy, and Immunology and program director of Allergy and Immunology, Virginia Commonwealth University (VCU), Richmond, “when mast cell activation events occur only in the skin, we refer to it as chronic urticaria and in the airways or conjunctiva of allergic individuals as allergic asthma, rhinitis, and/or conjunctivitis. The absence of specific criteria for mast cell activation in the GI [gastrointestinal] tract or CNS [central nervous system] neither rules in mast cell involvement nor does it rule out mast cell involvement. Thus, more research is needed to find better diagnostic criteria.”

Schwartz also pointed to a recent paper reporting the use of artificial intelligence models to “quantify diagnostic precision and specificity” of “alternative” MCAS definitions. The conclusion was a “lack of specificity is pronounced in relation to multiple control criteria, raising the concern that alternative criteria could disproportionately contribute to MCAS overdiagnosis, to the exclusion of more appropriate diagnoses.”

During the meeting, Afrin acknowledged that the broader view risks overdiagnosis of MCAS. However, he also referenced Occam’s razor, the principle that the simplest explanation is probably the best one. “Which scenario is more likely? Multiple diagnoses and problems that are all independent of each other vs one diagnosis that’s biologically capable of causing most or all of the findings, ie, the simplest solution even if it’s not the most immediately obvious solution?”

He said in an interview: “Do we have any proof that MCAS is what’s underlying hypermobile Ehlers-Danlos or POTS or chronic fatigue? No, we don’t have any proof, not because anybody has done studies that have shown there to be no connection but simply because we’re so early in our awareness that the disease even exists that the necessary studies haven’t even been done yet.”

At the meeting, Afrin introduced proposals to turn the “Masterminds” group into a formal professional society and to launch a journal. He also gave an update on progress in developing a symptom assessment tool both for clinical use and to enable clinical trials of new drugs to target mast cells or their mediators. The plan is to field test the tool in 2025 and publish those results in 2026. 

Grach, Afrin, and Chang had no disclosures. Schwartz discovered tryptase and invented the Thermo Fisher tryptase assay, for which his institution (VCU) receives royalties that are shared with him. He also invented monoclonal antibodies used for detecting mast cells or basophils, for which VCU receives royalties from several companies, including Millipore, Santa Cruz, BioLegend, and Hycult Biotech, that are also shared with him. He is a paid consultant for Blueprint Medicines, Celldex Therapeutics, Invea, Third Harmonic Bio, HYCOR Biomedical, Jasper, TerSera Therapeutics, and GLG. He also serves on an AstraZeneca data safety monitoring board for a clinical trial involving benralizumab treatment of hypereosinophilic syndrome and receives royalties from UpToDate (biomarkers for anaphylaxis) and Goldman-Cecil Medicine (anaphylaxis).

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

Depending on one’s perspective, “mast cell activation syndrome (MCAS)” is either a relatively rare, narrowly defined severe allergic condition or a vastly underrecognized underlying cause of multiple chronic inflammatory conditions that affect roughly 17% of the entire population. 

Inappropriate activation of mast cells — now termed mast cell activation disease (MCAD) — has long been known to underlie allergic symptoms and inflammation, and far less commonly, neoplasias such as mastocytosis. The concept of chronic, persistent MCAS associated with aberrant growth and dystrophism is more recent, emerging only in the last couple of decades as a separate entity under the MCAD heading. 

Observational studies and clinical experience have linked signs and symptoms of MCAS with other inflammatory chronic conditions such as hypermobile Ehlers-Danlos Syndrome (EDS), postural orthostatic tachycardia syndrome (POTS), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and recently, long COVID. However, those conditions themselves are diagnostically challenging, and as yet there is no proof of causation.

The idea that MCAS is the entity — or at least, a key one — at the center of “a confoundingly, extraordinarily heterogeneous chronic multisystem polymorbidity” was the theme of a recent 4-day meeting of a professional group informally dubbed “Masterminds.” Since their first meeting in 2018, the group has grown from about 35 to nearly 650 multidisciplinary professionals. 

Stephanie L. Grach, MD, assistant professor of medicine at the Mayo Clinic, Rochester, Minnesota, gave an introductory talk about the importance of changing “the medical paradigm around complex chronic illness.” Much of the rest of the meeting was devoted to sharing approaches for managing MCAS comorbidities, including dysautonomia, hypermobility, and associated craniocervical dysfunction, and various other multi-system conditions characterized by chronic pain and/or fatigue. Several talks covered the use of agents that block mast cell activity as potential treatment. 

In an interview, Grach said “the meeting was an exciting example of how not only research, but also medicine, is moving forward, and it’s really cool to see that people are independently coming to very similar conclusions about shared pathologies, and because of that, the importance of overlap amongst complex medical conditions that historically have really been poorly addressed.”

She added, “mast cell activation, or mast cell hyperactivity, is one part of the greater picture. What’s important about the mast cell component is that of the multiple different targetable pathologies, it’s one that currently has potential available therapies that can be explored, some of them relatively easily.”

But Christopher Chang, MD, PhD, chief of the Pediatric Allergy and Immunology program, Joe DiMaggio Children’s Hospital, Hollywood, Florida, sees it differently. In an interview, he noted that the reason for disagreement over what constitutes MCAS is that “it doesn’t have a lot of objective findings that we can identify. ... We know that mast cells are important immune cells, just like all immune cells are important. It seems like whenever someone has unexplained symptoms, people try to blame it on mast cells. But it’s very hard to prove that.” 
 

Two Definitions Characterize the Illness Differently

One proposed “consensus” MCAS definition was first published in 2011 by a group led by hematologist Peter Valent, MD, of the Medical University of Vienna in Austria. It has been revised since, and similar versions adopted by medical societies, including the American Academy of Allergy, Asthma & Immunology (AAAAI). The most recent versions propose three core MCAS criteria: 

• Typical clinical signs of severe, recurrent (episodic) systemic (at least two organ systems) MCA are present (often in the form of anaphylaxis).
• The involvement of mast cells (MCs) is documented by biochemical studies, preferably an increase in serum tryptase levels from the individual’s baseline to plus 20% + 2 ng/mL.
• Response of symptoms to therapy with MC-stabilizing agents, drugs directed against MC mediator production, or drugs blocking mediator release or effects of MC-derived mediators.

The following year, a separate publication authored by Gerhard J. Molderings, MD, University of Bonn in Germany, and colleagues proposed a much broader MCAS definition. Also revised since, the latest “consensus-2” was published in 2020. This definition consists of one major criterion: “A constellation of clinical complaints attributable to pathologically increased MC activity, ie, MC mediator release syndrome.” This “constellation” involves conditions of nearly every organ system that, taken together, are estimated to affect up to 17% of the entire population. These are just a few examples: 

• Constitutional: Chronic fatigue, flushing, or sweats
• Dermatologic: Rashes or lesions
• Ophthalmologic: dry eyes
• Oral: Burning or itching in mouth
• Pulmonary: Airway inflammation at any/all levels
• Cardiovascular: Blood pressure lability or codiagnosis of POTS is common
• Gastrointestinal: Reflux, dysphagia, or malabsorption
• Genitourinary: Endometriosis, dysmenorrhea, or dyspareunia
• Musculoskeletal/connective tissue: Fibromyalgia or diagnosis of hypermobile EDS is common
• Neurologic: Headaches or sensory neuropathies
• Psychiatric: Depression or anxiety
• Endocrinologic: Thyroid disease or dyslipidemia
• Hematologic: Polycythemia or anemia (after ruling out other causes)

The diagnosis is made by fulfilling that major criterion, plus at least one objective assessment of pathologically increased release of MC mediators, including infiltrates, abnormal MC morphology, or MC genetic changes shown to increase MC activity. Other alternatives include evidence of above-normal levels of MC mediators, including tryptase, histamine or its metabolites, heparin, or chromatin A, in whole blood, serum, plasma, or urine. Symptomatic response to MC activation inhibitors can also be used but isn’t required as it is in the other definition. 
 

Underdiagnosis vs Overdiagnosis

Lawrence B. Afrin, MD, senior consultant in hematology/oncology at the AIM Center for Personalized Medicine, Westchester, New York, and lead author of the 2020 update of the broader “consensus-2” criteria, said in an interview, “we now know MCAS exists, and it’s prevalent, even though, for understandable and forgivable reasons, we’ve been missing it all along. ... If you see a patient who has this chronic, multisystem unwellness with general themes of inflammation plus or minus allergic issues and you can’t find some other rational explanation that better accounts for what’s going on ... then it’s reasonable to think to include MCAS in the differential diagnosis. If the patient happens not to fit the diagnostic criteria being advanced by one group, that doesn’t necessarily rule out the possibility that this is still going on.”

Afrin, along with his coauthors, faulted the narrower “consensus-1” definition for lacking data to support the “20% + 2” criteria for requiring the difficult determination of a patient’s “baseline” and for requiring evidence of response to treatment prior to making the diagnosis. Not all patients will respond to a given histamine blocker, he noted. 

But Lawrence B. Schwartz, MD, PhD, an author on both the Valent and AAAAI criteria, disagreed, noting that the narrower criteria “appear to have a high degree of specificity and sensitivity when the reaction is systemic and involves hypotension. Less severe clinical events, particularly involving the gastrointestinal or central nervous systems, do not have precise clinical or biomarker criteria for identifying mast cell involvement.” 

Added Schwartz, who is professor of medicine and chair of the Division of Rheumatology, Allergy, and Immunology and program director of Allergy and Immunology, Virginia Commonwealth University (VCU), Richmond, “when mast cell activation events occur only in the skin, we refer to it as chronic urticaria and in the airways or conjunctiva of allergic individuals as allergic asthma, rhinitis, and/or conjunctivitis. The absence of specific criteria for mast cell activation in the GI [gastrointestinal] tract or CNS [central nervous system] neither rules in mast cell involvement nor does it rule out mast cell involvement. Thus, more research is needed to find better diagnostic criteria.”

Schwartz also pointed to a recent paper reporting the use of artificial intelligence models to “quantify diagnostic precision and specificity” of “alternative” MCAS definitions. The conclusion was a “lack of specificity is pronounced in relation to multiple control criteria, raising the concern that alternative criteria could disproportionately contribute to MCAS overdiagnosis, to the exclusion of more appropriate diagnoses.”

During the meeting, Afrin acknowledged that the broader view risks overdiagnosis of MCAS. However, he also referenced Occam’s razor, the principle that the simplest explanation is probably the best one. “Which scenario is more likely? Multiple diagnoses and problems that are all independent of each other vs one diagnosis that’s biologically capable of causing most or all of the findings, ie, the simplest solution even if it’s not the most immediately obvious solution?”

He said in an interview: “Do we have any proof that MCAS is what’s underlying hypermobile Ehlers-Danlos or POTS or chronic fatigue? No, we don’t have any proof, not because anybody has done studies that have shown there to be no connection but simply because we’re so early in our awareness that the disease even exists that the necessary studies haven’t even been done yet.”

At the meeting, Afrin introduced proposals to turn the “Masterminds” group into a formal professional society and to launch a journal. He also gave an update on progress in developing a symptom assessment tool both for clinical use and to enable clinical trials of new drugs to target mast cells or their mediators. The plan is to field test the tool in 2025 and publish those results in 2026. 

Grach, Afrin, and Chang had no disclosures. Schwartz discovered tryptase and invented the Thermo Fisher tryptase assay, for which his institution (VCU) receives royalties that are shared with him. He also invented monoclonal antibodies used for detecting mast cells or basophils, for which VCU receives royalties from several companies, including Millipore, Santa Cruz, BioLegend, and Hycult Biotech, that are also shared with him. He is a paid consultant for Blueprint Medicines, Celldex Therapeutics, Invea, Third Harmonic Bio, HYCOR Biomedical, Jasper, TerSera Therapeutics, and GLG. He also serves on an AstraZeneca data safety monitoring board for a clinical trial involving benralizumab treatment of hypereosinophilic syndrome and receives royalties from UpToDate (biomarkers for anaphylaxis) and Goldman-Cecil Medicine (anaphylaxis).

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

TOPLINE:

Both low and high levels of maternal 25-hydroxy [25(OH)] vitamin D are linked to an increased risk for adverse pregnancy outcomes in women with systemic lupus erythematosus (SLE), with levels of 40-59 ng/mL being associated with the lowest risk.

METHODOLOGY:

• Researchers analyzed 260 pregnancies in the Hopkins Lupus Cohort to examine the association between 25(OH) vitamin D levels and adverse pregnancy outcomes in women with SLE.
• The participants were required to have serum vitamin D levels measured during pregnancy and pregnancy-related outcomes data.
• The 25(OH) vitamin D levels were measured at visits every 6 weeks, and the participants were divided into six subgroups on the basis of the mean 25(OH) vitamin D levels: < 20 ng/dL, 20-29 ng/dL, 30-39 ng/dL, 40-49 ng/dL, 50-59 ng/dL, and ≥ 60 ng/dL.
• The adverse pregnancy outcomes included miscarriage, preterm delivery, and restricted intrauterine growth of the fetus.
• This study used a time-to-event analysis to assess the association between time-varying 25(OH) vitamin D levels and adverse pregnancy outcomes.

TAKEAWAY:

• Adverse pregnancy outcomes were observed in 45.3% of pregnancies; the risks for miscarriage and preterm delivery were significantly different across the six subgroups with varying vitamin D levels (P = .0045 and P = .0007, respectively).
• A U-shaped curve association was observed between vitamin D levels and adverse pregnancy outcomes, with the highest risk seen in patients with the lowest or highest levels of vitamin D during pregnancy, while the lowest risk was seen in those with vitamin D levels between 40 and 59 ng/mL.
• Low 25(OH) vitamin D levels during the second trimester resulted in premature delivery in 9 out of 10 pregnancies; however, a relationship between vitamin D levels in the first trimester and pregnancy outcomes was not observed.
• The time-to-event analysis showed that the U-shaped association between vitamin D levels and adverse pregnancy outcomes was still observed even after accounting for lupus disease activity; however, the elevated risk seen in individuals with the highest levels of vitamin D was no longer statistically significant.

IN PRACTICE:

“We recommend monitoring of maternal serum 25(OH) vitamin D levels throughout SLE pregnancies and supplementing patients with vitamin D insufficiency or deficiency, aiming for 25(OH) vitamin D range of 40-59 ng/mL. Over supplementation should be avoided,” the authors wrote.

SOURCE:

The study was led by Nima Madanchi, MD, Johns Hopkins University, Baltimore, and was published online on September 23, 2024, in Arthritis Care & Research.

LIMITATIONS:

This study could not prove a cause-and-effect relationship between vitamin D levels and adverse pregnancy outcomes. This study included only clinically identified pregnancies, potentially missing very early miscarriages. It also could not adjust for parity due to the unknown parity of the index pregnancy.

DISCLOSURES:

This Hopkins Lupus Cohort was supported by grants from the National Institutes of Health. The authors declared no conflicts of interest.
 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Both low and high levels of maternal 25-hydroxy [25(OH)] vitamin D are linked to an increased risk for adverse pregnancy outcomes in women with systemic lupus erythematosus (SLE), with levels of 40-59 ng/mL being associated with the lowest risk.

METHODOLOGY:

• Researchers analyzed 260 pregnancies in the Hopkins Lupus Cohort to examine the association between 25(OH) vitamin D levels and adverse pregnancy outcomes in women with SLE.
• The participants were required to have serum vitamin D levels measured during pregnancy and pregnancy-related outcomes data.
• The 25(OH) vitamin D levels were measured at visits every 6 weeks, and the participants were divided into six subgroups on the basis of the mean 25(OH) vitamin D levels: < 20 ng/dL, 20-29 ng/dL, 30-39 ng/dL, 40-49 ng/dL, 50-59 ng/dL, and ≥ 60 ng/dL.
• The adverse pregnancy outcomes included miscarriage, preterm delivery, and restricted intrauterine growth of the fetus.
• This study used a time-to-event analysis to assess the association between time-varying 25(OH) vitamin D levels and adverse pregnancy outcomes.

TAKEAWAY:

• Adverse pregnancy outcomes were observed in 45.3% of pregnancies; the risks for miscarriage and preterm delivery were significantly different across the six subgroups with varying vitamin D levels (P = .0045 and P = .0007, respectively).
• A U-shaped curve association was observed between vitamin D levels and adverse pregnancy outcomes, with the highest risk seen in patients with the lowest or highest levels of vitamin D during pregnancy, while the lowest risk was seen in those with vitamin D levels between 40 and 59 ng/mL.
• Low 25(OH) vitamin D levels during the second trimester resulted in premature delivery in 9 out of 10 pregnancies; however, a relationship between vitamin D levels in the first trimester and pregnancy outcomes was not observed.
• The time-to-event analysis showed that the U-shaped association between vitamin D levels and adverse pregnancy outcomes was still observed even after accounting for lupus disease activity; however, the elevated risk seen in individuals with the highest levels of vitamin D was no longer statistically significant.

IN PRACTICE:

“We recommend monitoring of maternal serum 25(OH) vitamin D levels throughout SLE pregnancies and supplementing patients with vitamin D insufficiency or deficiency, aiming for 25(OH) vitamin D range of 40-59 ng/mL. Over supplementation should be avoided,” the authors wrote.

SOURCE:

The study was led by Nima Madanchi, MD, Johns Hopkins University, Baltimore, and was published online on September 23, 2024, in Arthritis Care & Research.

LIMITATIONS:

This study could not prove a cause-and-effect relationship between vitamin D levels and adverse pregnancy outcomes. This study included only clinically identified pregnancies, potentially missing very early miscarriages. It also could not adjust for parity due to the unknown parity of the index pregnancy.

DISCLOSURES:

This Hopkins Lupus Cohort was supported by grants from the National Institutes of Health. The authors declared no conflicts of interest.
 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Both low and high levels of maternal 25-hydroxy [25(OH)] vitamin D are linked to an increased risk for adverse pregnancy outcomes in women with systemic lupus erythematosus (SLE), with levels of 40-59 ng/mL being associated with the lowest risk.

METHODOLOGY:

• Researchers analyzed 260 pregnancies in the Hopkins Lupus Cohort to examine the association between 25(OH) vitamin D levels and adverse pregnancy outcomes in women with SLE.
• The participants were required to have serum vitamin D levels measured during pregnancy and pregnancy-related outcomes data.
• The 25(OH) vitamin D levels were measured at visits every 6 weeks, and the participants were divided into six subgroups on the basis of the mean 25(OH) vitamin D levels: < 20 ng/dL, 20-29 ng/dL, 30-39 ng/dL, 40-49 ng/dL, 50-59 ng/dL, and ≥ 60 ng/dL.
• The adverse pregnancy outcomes included miscarriage, preterm delivery, and restricted intrauterine growth of the fetus.
• This study used a time-to-event analysis to assess the association between time-varying 25(OH) vitamin D levels and adverse pregnancy outcomes.

TAKEAWAY:

• Adverse pregnancy outcomes were observed in 45.3% of pregnancies; the risks for miscarriage and preterm delivery were significantly different across the six subgroups with varying vitamin D levels (P = .0045 and P = .0007, respectively).
• A U-shaped curve association was observed between vitamin D levels and adverse pregnancy outcomes, with the highest risk seen in patients with the lowest or highest levels of vitamin D during pregnancy, while the lowest risk was seen in those with vitamin D levels between 40 and 59 ng/mL.
• Low 25(OH) vitamin D levels during the second trimester resulted in premature delivery in 9 out of 10 pregnancies; however, a relationship between vitamin D levels in the first trimester and pregnancy outcomes was not observed.
• The time-to-event analysis showed that the U-shaped association between vitamin D levels and adverse pregnancy outcomes was still observed even after accounting for lupus disease activity; however, the elevated risk seen in individuals with the highest levels of vitamin D was no longer statistically significant.

IN PRACTICE:

“We recommend monitoring of maternal serum 25(OH) vitamin D levels throughout SLE pregnancies and supplementing patients with vitamin D insufficiency or deficiency, aiming for 25(OH) vitamin D range of 40-59 ng/mL. Over supplementation should be avoided,” the authors wrote.

SOURCE:

The study was led by Nima Madanchi, MD, Johns Hopkins University, Baltimore, and was published online on September 23, 2024, in Arthritis Care & Research.

LIMITATIONS:

This study could not prove a cause-and-effect relationship between vitamin D levels and adverse pregnancy outcomes. This study included only clinically identified pregnancies, potentially missing very early miscarriages. It also could not adjust for parity due to the unknown parity of the index pregnancy.

DISCLOSURES:

This Hopkins Lupus Cohort was supported by grants from the National Institutes of Health. The authors declared no conflicts of interest.
 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Older adults with antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis face a higher risk for end-stage renal disease or mortality and severe infections. However, frailty, more than age, predicts severe infections within 2 years of diagnosis.

METHODOLOGY:

• Researchers conducted a retrospective cohort study using data from the Mass General Brigham ANCA-associated vasculitis cohort in the United States.
• They included 234 individuals (median age, 75 years) with incident ANCA-associated vasculitis who were treated from January 2002 to December 2019.
• Baseline frailty was measured using a claims-based frailty index, with data collected in the year before treatment initiation; individuals were categorized as those who were nonfrail, prefrail, mildly frail, and moderately to severely frail.
• Frailty, either mild or moderate to severe, was noted in 44 of 118 individuals aged ≥ 75 years and in 25 of 116 individuals aged 65-74 years.
• The outcomes of interest were the incidences of end-stage renal disease or death and severe infections within 2 years of diagnosis. The association of age and frailty with clinical outcomes was assessed in those aged 65-74 years and ≥ 75 years.

TAKEAWAY:

• Frailty was a significant predictor of severe infections within 2 years of ANCA-associated vasculitis diagnosis (adjusted hazard ratio [aHR], 8.46; 95% CI, 3.95-18.14), showing a stronger association than seen for chronological age ≥ 75 years (aHR, 2.52; 95% CI, 1.26-5.04).
• The incidence of severe infections was higher in those with vs without frailty in the age groups 65-74 years (38.9 vs 0.8 cases per 100 person-years) and ≥ 75 years (61.9 vs 12.3 cases per 100 person-years).
• Older age (≥ 75 years) was associated with an increased risk for end-stage renal disease or death (aHR, 4.50; 95% CI, 1.83-11.09); however, frailty was not.
• The effect of frailty on end-stage renal disease or death varied by age, with a larger difference observed in individuals aged 65-74 years (frail vs nonfrail, 7.5 vs 2.0 cases per 100 person-years) than in those aged ≥ 75 years (13.5 vs 16.0 cases per 100 person-years).

IN PRACTICE:

“Our results highlight the fact that assessment of frailty in the care of older adults with ANCA-associated vasculitis can distinguish a group of patients at increased risk of severe infections who might benefit from interventions to minimize infection risk and optimize outcomes,” the authors wrote.

“Incorporating frailty screening into the management of ANCA-associated vasculitis provides an opportunity to offer personalized, evidence-based care to frail older adults,” Alexandra Legge, MD, Dalhousie University, Halifax, Nova Scotia, Canada, wrote in an associated comment published online in The Lancet Rheumatology.
 

SOURCE:

This study was led by Sebastian E. Sattui, MD, Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh in Pennsylvania. It was published online on September 18, 2024, in The Lancet Rheumatology.

LIMITATIONS:

The study’s observational design and single-center setting limited the generalizability of the findings. Residual confounding may have been possible despite adjustments for relevant baseline factors. The requirement of at least one healthcare encounter before baseline may have underrepresented individuals without frailty. Differences in treatment patterns after the baseline period were not controlled for.

DISCLOSURES:

The study was supported by the National Institutes of Health and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Some authors reported receiving grants, research support, consulting fees, honoraria, or royalties or serving on advisory boards of pharmaceutical companies and other sources outside of the submitted work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Older adults with antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis face a higher risk for end-stage renal disease or mortality and severe infections. However, frailty, more than age, predicts severe infections within 2 years of diagnosis.

METHODOLOGY:

• Researchers conducted a retrospective cohort study using data from the Mass General Brigham ANCA-associated vasculitis cohort in the United States.
• They included 234 individuals (median age, 75 years) with incident ANCA-associated vasculitis who were treated from January 2002 to December 2019.
• Baseline frailty was measured using a claims-based frailty index, with data collected in the year before treatment initiation; individuals were categorized as those who were nonfrail, prefrail, mildly frail, and moderately to severely frail.
• Frailty, either mild or moderate to severe, was noted in 44 of 118 individuals aged ≥ 75 years and in 25 of 116 individuals aged 65-74 years.
• The outcomes of interest were the incidences of end-stage renal disease or death and severe infections within 2 years of diagnosis. The association of age and frailty with clinical outcomes was assessed in those aged 65-74 years and ≥ 75 years.

TAKEAWAY:

• Frailty was a significant predictor of severe infections within 2 years of ANCA-associated vasculitis diagnosis (adjusted hazard ratio [aHR], 8.46; 95% CI, 3.95-18.14), showing a stronger association than seen for chronological age ≥ 75 years (aHR, 2.52; 95% CI, 1.26-5.04).
• The incidence of severe infections was higher in those with vs without frailty in the age groups 65-74 years (38.9 vs 0.8 cases per 100 person-years) and ≥ 75 years (61.9 vs 12.3 cases per 100 person-years).
• Older age (≥ 75 years) was associated with an increased risk for end-stage renal disease or death (aHR, 4.50; 95% CI, 1.83-11.09); however, frailty was not.
• The effect of frailty on end-stage renal disease or death varied by age, with a larger difference observed in individuals aged 65-74 years (frail vs nonfrail, 7.5 vs 2.0 cases per 100 person-years) than in those aged ≥ 75 years (13.5 vs 16.0 cases per 100 person-years).

IN PRACTICE:

“Our results highlight the fact that assessment of frailty in the care of older adults with ANCA-associated vasculitis can distinguish a group of patients at increased risk of severe infections who might benefit from interventions to minimize infection risk and optimize outcomes,” the authors wrote.

“Incorporating frailty screening into the management of ANCA-associated vasculitis provides an opportunity to offer personalized, evidence-based care to frail older adults,” Alexandra Legge, MD, Dalhousie University, Halifax, Nova Scotia, Canada, wrote in an associated comment published online in The Lancet Rheumatology.
 

SOURCE:

This study was led by Sebastian E. Sattui, MD, Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh in Pennsylvania. It was published online on September 18, 2024, in The Lancet Rheumatology.

LIMITATIONS:

The study’s observational design and single-center setting limited the generalizability of the findings. Residual confounding may have been possible despite adjustments for relevant baseline factors. The requirement of at least one healthcare encounter before baseline may have underrepresented individuals without frailty. Differences in treatment patterns after the baseline period were not controlled for.

DISCLOSURES:

The study was supported by the National Institutes of Health and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Some authors reported receiving grants, research support, consulting fees, honoraria, or royalties or serving on advisory boards of pharmaceutical companies and other sources outside of the submitted work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Older adults with antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis face a higher risk for end-stage renal disease or mortality and severe infections. However, frailty, more than age, predicts severe infections within 2 years of diagnosis.

METHODOLOGY:

• Researchers conducted a retrospective cohort study using data from the Mass General Brigham ANCA-associated vasculitis cohort in the United States.
• They included 234 individuals (median age, 75 years) with incident ANCA-associated vasculitis who were treated from January 2002 to December 2019.
• Baseline frailty was measured using a claims-based frailty index, with data collected in the year before treatment initiation; individuals were categorized as those who were nonfrail, prefrail, mildly frail, and moderately to severely frail.
• Frailty, either mild or moderate to severe, was noted in 44 of 118 individuals aged ≥ 75 years and in 25 of 116 individuals aged 65-74 years.
• The outcomes of interest were the incidences of end-stage renal disease or death and severe infections within 2 years of diagnosis. The association of age and frailty with clinical outcomes was assessed in those aged 65-74 years and ≥ 75 years.

TAKEAWAY:

• Frailty was a significant predictor of severe infections within 2 years of ANCA-associated vasculitis diagnosis (adjusted hazard ratio [aHR], 8.46; 95% CI, 3.95-18.14), showing a stronger association than seen for chronological age ≥ 75 years (aHR, 2.52; 95% CI, 1.26-5.04).
• The incidence of severe infections was higher in those with vs without frailty in the age groups 65-74 years (38.9 vs 0.8 cases per 100 person-years) and ≥ 75 years (61.9 vs 12.3 cases per 100 person-years).
• Older age (≥ 75 years) was associated with an increased risk for end-stage renal disease or death (aHR, 4.50; 95% CI, 1.83-11.09); however, frailty was not.
• The effect of frailty on end-stage renal disease or death varied by age, with a larger difference observed in individuals aged 65-74 years (frail vs nonfrail, 7.5 vs 2.0 cases per 100 person-years) than in those aged ≥ 75 years (13.5 vs 16.0 cases per 100 person-years).

IN PRACTICE:

“Our results highlight the fact that assessment of frailty in the care of older adults with ANCA-associated vasculitis can distinguish a group of patients at increased risk of severe infections who might benefit from interventions to minimize infection risk and optimize outcomes,” the authors wrote.

“Incorporating frailty screening into the management of ANCA-associated vasculitis provides an opportunity to offer personalized, evidence-based care to frail older adults,” Alexandra Legge, MD, Dalhousie University, Halifax, Nova Scotia, Canada, wrote in an associated comment published online in The Lancet Rheumatology.
 

SOURCE:

This study was led by Sebastian E. Sattui, MD, Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh in Pennsylvania. It was published online on September 18, 2024, in The Lancet Rheumatology.

LIMITATIONS:

The study’s observational design and single-center setting limited the generalizability of the findings. Residual confounding may have been possible despite adjustments for relevant baseline factors. The requirement of at least one healthcare encounter before baseline may have underrepresented individuals without frailty. Differences in treatment patterns after the baseline period were not controlled for.

DISCLOSURES:

The study was supported by the National Institutes of Health and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Some authors reported receiving grants, research support, consulting fees, honoraria, or royalties or serving on advisory boards of pharmaceutical companies and other sources outside of the submitted work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.