Ankylosing spondylitis

TOPLINE:

Patients with late-onset axial spondyloarthritis (axSpA) are less likely to be positive for human leukocyte antigen B27 (HLA-B27) and have a family history of SpA; they are more likely to present with peripheral arthritis.

METHODOLOGY:

• Researchers conducted a multicenter cross-sectional study including 2165 patients with a clinical diagnosis of axSpA who were identified from the Rheumatic Diseases Portuguese Register from June 2008 to December 2022.
• Patients with symptom onset at or after 45 years of age were referred as late-onset axSpA, whereas those with symptom onset before 45 years as early-onset axSpA.
• Overall, 273 had a diagnosis of late-onset axSpA (mean age at symptom onset, 51.4 years; 55% men) and 1892 had a diagnosis of early-onset axSpA (mean age at symptom onset, 28.9 years; 56% men).
• Independent associations between demographic, clinical, imaging, and treatment characteristics and late-onset axSpA were tested using multivariable logistic regression models.

TAKEAWAY:

• Patients with late-onset axSpA were less likely to be positive for HLA-B27 (51% vs 65%; P < .001) and to have a family history of SpA (8% vs 14%; P < .01), have inflammatory back pain (81% vs 88%; P < .01), and have acute anterior uveitis (13% vs 20%; P < .01) than those with early-onset axSpA.
• Patients with late-onset axSpA had a higher likelihood of having peripheral arthritis than those with early-onset axSpA (36% vs 28%; P < .05).
• The odds of having late-onset axSpA were lower in patients with HLA-B27 positivity (adjusted odds ratio [aOR], 0.6; 95% CI, 0.4-0.7), a family history of SpA (aOR, 0.6; 95% CI, 0.4-0.9), inflammatory back pain (aOR, 0.5; 95% CI, 0.4-0.8), and acute anterior uveitis (aOR, 0.6; 95% CI, 0.4-0.9).
• Conversely, patients with peripheral arthritis had a higher likelihood of developing late-onset axSpA (aOR, 1.5; 95% CI, 1.1-1.9).

IN PRACTICE:

“In this study, we found that [late-onset axSpA] may represent a distinct phenotype with a weaker association with HLA-B27,” the authors wrote. “Whether [late-onset axSpA] comprises a subset of axSpA with a (possibly) different genetic or epigenetic background or rather translates difficulties in recognizing a less typical disease presentation and a population without a genetic marker which can make the diagnostic process more challenging merits further investigation.”

SOURCE:

The study was led by Margarida Lucas Rocha, MD, Department of Rheumatology, ULSA, Faro, Portugal. It was published online in Joint Bone Spine.

LIMITATIONS:

No limitations were reported in the study.

DISCLOSURES:

No relevant funding information and conflicts of interest were disclosed by the authors.

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 late-onset axial spondyloarthritis (axSpA) are less likely to be positive for human leukocyte antigen B27 (HLA-B27) and have a family history of SpA; they are more likely to present with peripheral arthritis.

METHODOLOGY:

• Researchers conducted a multicenter cross-sectional study including 2165 patients with a clinical diagnosis of axSpA who were identified from the Rheumatic Diseases Portuguese Register from June 2008 to December 2022.
• Patients with symptom onset at or after 45 years of age were referred as late-onset axSpA, whereas those with symptom onset before 45 years as early-onset axSpA.
• Overall, 273 had a diagnosis of late-onset axSpA (mean age at symptom onset, 51.4 years; 55% men) and 1892 had a diagnosis of early-onset axSpA (mean age at symptom onset, 28.9 years; 56% men).
• Independent associations between demographic, clinical, imaging, and treatment characteristics and late-onset axSpA were tested using multivariable logistic regression models.

TAKEAWAY:

• Patients with late-onset axSpA were less likely to be positive for HLA-B27 (51% vs 65%; P < .001) and to have a family history of SpA (8% vs 14%; P < .01), have inflammatory back pain (81% vs 88%; P < .01), and have acute anterior uveitis (13% vs 20%; P < .01) than those with early-onset axSpA.
• Patients with late-onset axSpA had a higher likelihood of having peripheral arthritis than those with early-onset axSpA (36% vs 28%; P < .05).
• The odds of having late-onset axSpA were lower in patients with HLA-B27 positivity (adjusted odds ratio [aOR], 0.6; 95% CI, 0.4-0.7), a family history of SpA (aOR, 0.6; 95% CI, 0.4-0.9), inflammatory back pain (aOR, 0.5; 95% CI, 0.4-0.8), and acute anterior uveitis (aOR, 0.6; 95% CI, 0.4-0.9).
• Conversely, patients with peripheral arthritis had a higher likelihood of developing late-onset axSpA (aOR, 1.5; 95% CI, 1.1-1.9).

IN PRACTICE:

“In this study, we found that [late-onset axSpA] may represent a distinct phenotype with a weaker association with HLA-B27,” the authors wrote. “Whether [late-onset axSpA] comprises a subset of axSpA with a (possibly) different genetic or epigenetic background or rather translates difficulties in recognizing a less typical disease presentation and a population without a genetic marker which can make the diagnostic process more challenging merits further investigation.”

SOURCE:

The study was led by Margarida Lucas Rocha, MD, Department of Rheumatology, ULSA, Faro, Portugal. It was published online in Joint Bone Spine.

LIMITATIONS:

No limitations were reported in the study.

DISCLOSURES:

No relevant funding information and conflicts of interest were disclosed by the authors.

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 late-onset axial spondyloarthritis (axSpA) are less likely to be positive for human leukocyte antigen B27 (HLA-B27) and have a family history of SpA; they are more likely to present with peripheral arthritis.

METHODOLOGY:

• Researchers conducted a multicenter cross-sectional study including 2165 patients with a clinical diagnosis of axSpA who were identified from the Rheumatic Diseases Portuguese Register from June 2008 to December 2022.
• Patients with symptom onset at or after 45 years of age were referred as late-onset axSpA, whereas those with symptom onset before 45 years as early-onset axSpA.
• Overall, 273 had a diagnosis of late-onset axSpA (mean age at symptom onset, 51.4 years; 55% men) and 1892 had a diagnosis of early-onset axSpA (mean age at symptom onset, 28.9 years; 56% men).
• Independent associations between demographic, clinical, imaging, and treatment characteristics and late-onset axSpA were tested using multivariable logistic regression models.

TAKEAWAY:

• Patients with late-onset axSpA were less likely to be positive for HLA-B27 (51% vs 65%; P < .001) and to have a family history of SpA (8% vs 14%; P < .01), have inflammatory back pain (81% vs 88%; P < .01), and have acute anterior uveitis (13% vs 20%; P < .01) than those with early-onset axSpA.
• Patients with late-onset axSpA had a higher likelihood of having peripheral arthritis than those with early-onset axSpA (36% vs 28%; P < .05).
• The odds of having late-onset axSpA were lower in patients with HLA-B27 positivity (adjusted odds ratio [aOR], 0.6; 95% CI, 0.4-0.7), a family history of SpA (aOR, 0.6; 95% CI, 0.4-0.9), inflammatory back pain (aOR, 0.5; 95% CI, 0.4-0.8), and acute anterior uveitis (aOR, 0.6; 95% CI, 0.4-0.9).
• Conversely, patients with peripheral arthritis had a higher likelihood of developing late-onset axSpA (aOR, 1.5; 95% CI, 1.1-1.9).

IN PRACTICE:

“In this study, we found that [late-onset axSpA] may represent a distinct phenotype with a weaker association with HLA-B27,” the authors wrote. “Whether [late-onset axSpA] comprises a subset of axSpA with a (possibly) different genetic or epigenetic background or rather translates difficulties in recognizing a less typical disease presentation and a population without a genetic marker which can make the diagnostic process more challenging merits further investigation.”

SOURCE:

The study was led by Margarida Lucas Rocha, MD, Department of Rheumatology, ULSA, Faro, Portugal. It was published online in Joint Bone Spine.

LIMITATIONS:

No limitations were reported in the study.

DISCLOSURES:

No relevant funding information and conflicts of interest were disclosed by the authors.

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.

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:

Tumor necrosis factor (TNF) inhibitors are associated with a reduced risk for recurrent cardiovascular events in patients with radiographic axial spondyloarthritis (axSpA) and a history of cardiovascular events.

METHODOLOGY:

• The researchers conducted a nationwide cohort study using data from the Korean National Claims Database, including 413 patients diagnosed with cardiovascular events following a radiographic axSpA diagnosis.
• Of all patients, 75 received TNF inhibitors (mean age, 51.9 years; 92% men) and 338 did not receive TNF inhibitors (mean age, 60.7 years; 74.9% men).
• Patients were followed from the date of the first cardiovascular event to the date of recurrence, the last date with claims data, or up to December 2021.
• The study outcome was recurrent cardiovascular events that occurred within 28 days of the first incidence and included myocardial infarction and stroke.
• The effect of TNF inhibitor exposure on the risk for recurrent cardiovascular events was assessed using an inverse probability weighted Cox regression analysis.

TAKEAWAY:

• The incidence of recurrent cardiovascular events in patients with radiographic axSpA was 32 per 1000 person-years.
• The incidence was 19 per 1000 person-years in the patients exposed to TNF inhibitors, whereas it was 36 per 1000 person-years in those not exposed to TNF inhibitors.
• Exposure to TNF inhibitors was associated with a 67% lower risk for recurrent cardiovascular events than non-exposure (P = .038).

IN PRACTICE:

“Our data add to previous knowledge by providing more direct evidence that TNFi [tumor necrosis factor inhibitors] could reduce the risk of recurrent cardiovascular events,” the authors wrote.
 

SOURCE:

The study was led by Oh Chan Kwon, MD, PhD, and Hye Sun Lee, PhD, Yonsei University College of Medicine, Seoul, South Korea. It was published online on October 4, 2024, in Arthritis Research & Therapy.

LIMITATIONS:

The lack of data on certain cardiovascular risk factors such as obesity, smoking, and lifestyle may have led to residual confounding. The patient count in the TNF inhibitor exposure group was not adequate to analyze each TNF inhibitor medication separately. The study included only Korean patients, limiting the generalizability to other ethnic populations. The number of recurrent stroke events was relatively small, making it infeasible to analyze myocardial infarction and stroke separately.

DISCLOSURES:

The study was funded by Yuhan Corporation as part of its “2023 Investigator Initiated Translation Research Program.” 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:

Tumor necrosis factor (TNF) inhibitors are associated with a reduced risk for recurrent cardiovascular events in patients with radiographic axial spondyloarthritis (axSpA) and a history of cardiovascular events.

METHODOLOGY:

• The researchers conducted a nationwide cohort study using data from the Korean National Claims Database, including 413 patients diagnosed with cardiovascular events following a radiographic axSpA diagnosis.
• Of all patients, 75 received TNF inhibitors (mean age, 51.9 years; 92% men) and 338 did not receive TNF inhibitors (mean age, 60.7 years; 74.9% men).
• Patients were followed from the date of the first cardiovascular event to the date of recurrence, the last date with claims data, or up to December 2021.
• The study outcome was recurrent cardiovascular events that occurred within 28 days of the first incidence and included myocardial infarction and stroke.
• The effect of TNF inhibitor exposure on the risk for recurrent cardiovascular events was assessed using an inverse probability weighted Cox regression analysis.

TAKEAWAY:

• The incidence of recurrent cardiovascular events in patients with radiographic axSpA was 32 per 1000 person-years.
• The incidence was 19 per 1000 person-years in the patients exposed to TNF inhibitors, whereas it was 36 per 1000 person-years in those not exposed to TNF inhibitors.
• Exposure to TNF inhibitors was associated with a 67% lower risk for recurrent cardiovascular events than non-exposure (P = .038).

IN PRACTICE:

“Our data add to previous knowledge by providing more direct evidence that TNFi [tumor necrosis factor inhibitors] could reduce the risk of recurrent cardiovascular events,” the authors wrote.
 

SOURCE:

The study was led by Oh Chan Kwon, MD, PhD, and Hye Sun Lee, PhD, Yonsei University College of Medicine, Seoul, South Korea. It was published online on October 4, 2024, in Arthritis Research & Therapy.

LIMITATIONS:

The lack of data on certain cardiovascular risk factors such as obesity, smoking, and lifestyle may have led to residual confounding. The patient count in the TNF inhibitor exposure group was not adequate to analyze each TNF inhibitor medication separately. The study included only Korean patients, limiting the generalizability to other ethnic populations. The number of recurrent stroke events was relatively small, making it infeasible to analyze myocardial infarction and stroke separately.

DISCLOSURES:

The study was funded by Yuhan Corporation as part of its “2023 Investigator Initiated Translation Research Program.” 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:

Tumor necrosis factor (TNF) inhibitors are associated with a reduced risk for recurrent cardiovascular events in patients with radiographic axial spondyloarthritis (axSpA) and a history of cardiovascular events.

METHODOLOGY:

• The researchers conducted a nationwide cohort study using data from the Korean National Claims Database, including 413 patients diagnosed with cardiovascular events following a radiographic axSpA diagnosis.
• Of all patients, 75 received TNF inhibitors (mean age, 51.9 years; 92% men) and 338 did not receive TNF inhibitors (mean age, 60.7 years; 74.9% men).
• Patients were followed from the date of the first cardiovascular event to the date of recurrence, the last date with claims data, or up to December 2021.
• The study outcome was recurrent cardiovascular events that occurred within 28 days of the first incidence and included myocardial infarction and stroke.
• The effect of TNF inhibitor exposure on the risk for recurrent cardiovascular events was assessed using an inverse probability weighted Cox regression analysis.

TAKEAWAY:

• The incidence of recurrent cardiovascular events in patients with radiographic axSpA was 32 per 1000 person-years.
• The incidence was 19 per 1000 person-years in the patients exposed to TNF inhibitors, whereas it was 36 per 1000 person-years in those not exposed to TNF inhibitors.
• Exposure to TNF inhibitors was associated with a 67% lower risk for recurrent cardiovascular events than non-exposure (P = .038).

IN PRACTICE:

“Our data add to previous knowledge by providing more direct evidence that TNFi [tumor necrosis factor inhibitors] could reduce the risk of recurrent cardiovascular events,” the authors wrote.
 

SOURCE:

The study was led by Oh Chan Kwon, MD, PhD, and Hye Sun Lee, PhD, Yonsei University College of Medicine, Seoul, South Korea. It was published online on October 4, 2024, in Arthritis Research & Therapy.

LIMITATIONS:

The lack of data on certain cardiovascular risk factors such as obesity, smoking, and lifestyle may have led to residual confounding. The patient count in the TNF inhibitor exposure group was not adequate to analyze each TNF inhibitor medication separately. The study included only Korean patients, limiting the generalizability to other ethnic populations. The number of recurrent stroke events was relatively small, making it infeasible to analyze myocardial infarction and stroke separately.

DISCLOSURES:

The study was funded by Yuhan Corporation as part of its “2023 Investigator Initiated Translation Research Program.” 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.

When Jennifer Welsh, a 40-year-old from New Britain, Connecticut, visited her doctor about pain in her joints and neck, her doctor sent her to the emergency department (ED) to rule out meningitis. The ED did rule that out, as well as strep, so Ms. Welsh went to her follow-up appointment a few days later, hoping for answers or at least more tests to get those answers.

Instead, the doctor — a different one from the same practice as her primary care physician (PCP) — wouldn’t even talk to Ms. Welsh about her symptoms because she couldn’t see the ED’s results and refused to view the results that Ms. Welsh could pull up online.

“She just completely shut me down,” Ms. Welsh recalled. “It was a really awful appointment, and I left in tears. I was in physical pain, I had just been to the ER, nothing is really resolved, I’m stressed out about it, and this woman is completely dismissing me.”

She had been able to schedule an appointment with her regular PCP later that week, but after the harrowing experience with this doctor, she wondered if her PCP would order the rheumatoid arthritis (RA) test that Ms. Welsh suspected she needed. So, she took matters into her own hands.

“I was searching for what test to ask for from my doctor,” she said, and she found that she could order it on her own from a major lab company she was already familiar with. For around $100, “I could get it done and see what it says on my own,” she said.

But that’s not how it worked out. Her regular PCP apologized for the other doctor’s behavior and ordered the RA test as well as additional tests — and got results while Ms. Welsh still waited for the one she ordered to arrive over a week later.

At first, Ms. Welsh was grateful she could order the RA test without her doctor’s referral. “I felt it gave me a sense of control over the situation that I felt really not in control of, until the system failed me, and I didn’t get the results,” she said. But then, “not having someone I could call and get an answer about why my tests were delayed, why I wasn’t able to access them, why it was taking so long — it was definitely anxiety-inducing.”
 

A Growing Market

Ms. Welsh is one of a growing number of patients who are ordering direct-to-consumer (DTC) lab tests without the recommendation or guidance of a doctor. They’re offered online by labs ranging from well-established giants like Quest and Labcorp to smaller, potentially less vetted companies, although some smaller companies contract with larger companies like Quest. Combined, the DTC market is projected to be worth $2 billion by 2025.

Yet the burgeoning industry has also drawn critiques from both bioethicists and privacy experts. A research letter in JAMA in 2023, for example, found that less than half of the 21 companies identified in an online search declared Health Insurance Portability and Accountability Act compliance, while more than half “indicated the potential use of consumer data for research purposes either internally or through third-party sharing.” That study found the most commonly offered tests were related to diabetes, the thyroid, and vitamin levels, and hormone tests for men and women, such as testosterone or estradiol.

But a number of companies also offer tests related to rheumatologic conditions. A handful of tests offered by Labcorp, for example, could be used in rheumatology, such as tests for celiac antibodies or high-sensitivity C-reactive protein. Quest similarly offers a handful of autoimmune-related tests. But other companies offer a long slate of autoimmune or antibody tests.

The antinuclear antibody (ANA) test and RA panel offered by Quest are the same tests, run and analyzed in the same labs, as those ordered by physicians and hospitals, according to James Faix, MD, the medical director of immunology at Quest Diagnostics. Their RA panel includes rheumatoid factor and anti-cyclic citrullinated peptide as well as antibody to mutated citrullinated vimentin, “which may detect approximately 10%-15%” of patients who test negative to the first two.

Quest’s ANA test with reflex costs $112, and its RA panel costs $110, price points that are similar across other companies’ offerings. Labcorp declined to respond to questions about its DTC tests, and several smaller companies did not respond to queries about their offerings. It can therefore be hard to assess what’s included or what the quality is of many DTC tests, particularly from smaller, less established companies.
 

Oversight and Quality Control

Anthony Killeen, MD, PhD, president of the Association for Diagnostics & Laboratory Medicine (ADLM) and director of Clinical Laboratories at the University of Minnesota Medical Center in Minneapolis, said via email that the ADLM supports “expanding consumer access to direct-to-consumer laboratory testing services that have demonstrated analytical and clinical validity and clinical utility,” given the importance of individuals learning about their health status and becoming more involved in health decisions. But the ADLM also recommends “that only CLIA-certified laboratories perform direct-to-consumer testing,” he said.

Association for Diagnostics &amp; Laboratory Medicine

“There are direct-to-consumer tests on the market that are not medical-grade laboratory tests and that may be performed in nonaccredited laboratories,” Dr. Killeen said. “We advise consumers to steer clear of such tests.” The ADLM also encourages consumers to “work with qualified healthcare providers when making decisions based off the results they receive from any direct-to-consumer tests” and recommends that DTC test companies “provide consumers with sufficient information and/or access to expert help to assist them in ordering tests and interpreting the results.”

Yet it’s unclear how much support, if any, consumers can receive in terms of understanding what their tests mean. Most of the companies in the 2023 study offered optional follow-up with a healthcare professional, but these professionals ranged from physicians to “health coaches,” and all the companies had disclaimers that “test results did not constitute medical advice.”

At Quest, the only company to respond to this news organization’s request for comment, consumer-initiated tests ordered online are first reviewed by a physician at PWNHealth, an independent, third-party physician network, to determine that it’s appropriate before the lab order is actually placed.

“Once results are available, individuals have the option to discuss their results with an independent physician at no extra cost,” Dr. Faix said. ANA or RA results outside the normal ranges may trigger a “call from a PWNHealth healthcare coordinator, who can help provide information, suggestions on next steps, and set up time for the individual to speak with an independent physician to discuss questions or concerns regarding the results,” he said.

“Our goal is not to replace the role of a healthcare provider,” Dr. Faix said. “We are providing an alternate way for people to engage with the healthcare system that offers convenience, gives people more control over their own healthcare journeys, and meets them where they are, supporting both consumers and their care teams.” The company has expanded its offerings from an initial 30 tests made available in 2018 to over 130 today, deciding which to offer “based on consumer research and expertise of clinical experts.” The company has also “seen steady interest in our two consumer rheumatology offerings,” Dr. Faix said.
 

The DTC Landscape in Rheumatology

Within rheumatology, among the most popular tests is for ANA, based on the experience of Alfred Kim, MD, PhD, associate professor of medicine at Washington University School of Medicine in St Louis, Missouri.

Dr. Kim

“For a lot of people, losing control over their health is maybe the most frightening experience they can have, so I think a lot of patients use this as a way to kind of have ownership over their health,” Dr. Kim said. “Let’s say they’ve been to four doctors. No one can explain what’s going on. They’re getting frustrated, and so they just turn to solutions where they feel like they have ownership over the situation.”

Though the market is undoubtedly growing, the growth appears uneven across geography and institution types. Kim has seen a “fair number of referrals,” with patients coming in with results from a DTC test. Michael Putman, MD, MSci, assistant professor of medicine at the Medical College of Wisconsin in Milwaukee, hasn’t seen it much. “I know that patients can get testing done themselves independently, but I don’t have people routinely coming in with tests they’ve ordered in advance of our appointment,” Dr. Putman said, but, like Dr. Kim, he recognizes why patients might seek them out.

Dr. Putman

Ron Hester Photography

Risks vs Benefits

DTC testing is not an answer to the national shortage of rheumatologists, however, especially given the risks that Dr. Niewold, Dr. Putman, and Dr. Kim worry outweigh potential benefits. On the one hand, getting online test results may help expedite a referral to a specialist, Dr. Niewold said. But a long wait for that appointment could then easily become a bigger source of anxiety than comfort, Dr. Putman said.

“It’s a trade-off where you are accepting a lot more people getting false-positive diagnoses and spending months thinking they have some disease where they might not, in exchange for a couple people who would have had a delayed diagnosis,” Dr. Putman said. “There’s an enormous amount of existential suffering,” that’s familiar to rheumatologists because some patients may dread the diagnosis of a rheumatic disease the way they might fear a cancer diagnosis, especially if they have lost a family member to a condition that they suspect they share, he said. “To put yourself into an existential catastrophe — that’s not a small harm.”

Dr. Niewold agreed, pointing out that patients with a positive ANA test may “get unnecessarily worried and stay up all night reading about lupus, getting scared for weeks on end before seeing a specialist.” And there are financial harms as well for patients who may order the same test multiple times, or a whole slate of tests, that they don’t need for hundreds or thousands of dollars. There’s also the lost time and effort of researching a condition or even seeking out support groups that patients may pursue, Dr. Niewold said.

The likely biggest risk to individuals, however, is the potential for overdiagnosis or misdiagnosis.

“If someone comes in and they’ve read the textbook on lupus and they have a positive ANA, it’s really hard as a rheumatologist to walk that back,” Dr. Putman said. “The human mind is a powerful thing,” he added, and people who get a positive test will likely start to notice things like joint pain or a rash on their cheeks and begin attributing it to a diagnosis they risk convincing themselves they have. “When people come into your clinic not knowing what a disease would look like and they just tell you how they’re feeling, it’s a much cleaner and more honest way to approach diagnosis.”

Most patients likely don’t realize, for example, that none of the tests rheumatologists usually order are diagnostic in and of themselves, Dr. Niewold said. “They’re all kind of like stars in the constellation of a diagnosis,” he said. “They’re helpful, but none of them is sufficient by itself.”

Dr. Killeen agreed, noting that “consumers might not understand the nuances of these tests well enough to know whether it is appropriate to order them or how to interpret the results correctly.” Given the long-term implications of a diagnosis for a rheumatologic disease, “I would have concerns about consumers ordering and interpreting rheumatologic tests without working closely with their physicians,” Dr. Killeen said. “The main concern that lab experts have about direct-to-consumer tests is the potential for people to get misleading results and/or to misinterpret their results, which in turn could lead to people not getting the treatment they need or getting treatment when they don’t need any at all.”

It’s one thing for patients to come in asking for a particular treatment they may not need but which a doctor may be able to dissuade them from seeking. But Dr. Kim also pointed out the risk that patients may decide to treat themselves with therapies that haven’t undergone rigorous testing or haven’t been recommended by a physician.

“We tend to have people who come in with a pretty clear idea of what they want done, but the problem is, we don’t know if their reasoning is correct from a clinical perspective,” Dr. Kim said. Companies offer these tests with the belief that they’re “providing patients a choice, an option to take ownership,” he said, “but the potential harm can be realized very quickly because there are going to be people who are misdiagnosing themselves and, worse yet, may then pursue their own treatment plan that’s going in the opposite direction of where we think it needs to go.”

Or, on the flip side, if a patient erroneously believes they have the answer to what ails them, it may delay diagnosis of a more serious condition that’s rarer or harder to detect. Kim pointed to, for example, intravascular lymphoma, which is notoriously as difficult to identify as it is rare and aggressive. If a patient’s confirmation bias has led them to believe they have an autoimmune condition, they may not receive the more serious diagnosis until it’s advanced too far to treat.
 

Patient-Provider Relationship Friction

Another concern is how these tests may lead to confusion and frustration that can erode the patient-provider relationship, particularly because most patients don’t know how to interpret the results or understand the bigger context in which the results have to be interpreted. Many patients may think a test can come back with a binary answer, a positive or negative, and that means they do or don’t have a condition. That’s generally true for pregnancy tests, COVID tests, and sexually transmitted infection tests — the kinds of tests that have long been available to consumers and which have fairly straightforward answers.

But physicians know that’s not the case for many conditions, particularly those in rheumatology.

“In rheumatic diseases, because the tests have such marginal value in terms of diagnosis, almost always we develop a suspicion before we even think about ordering the tests, and then that dictates whether or not we cross that threshold,” Dr. Kim said. “A negative test doesn’t exclude the fact that you may have disease X, but a positive test also doesn’t mean you have disease X. All they provide is an idea of the risk.”

But some patients who come in with DTC test results have “already made the decision in their mind that they have a certain condition,” Dr. Kim said. “This is obviously dangerous because the majority of these patients do not have the condition they think they have, and it leaves a very uncomfortable feeling after the visit because they feel like they’ve been either betrayed by me or by the test, and they leave more confused.”

Patients may also come in with tests that a doctor isn’t familiar with or isn’t sure how to interpret on its own, at least for that particular patient.

“For ANA testing, we have a pretty good idea of its positive and negative predictive value because it’s ordered so much, but for many of these tests being offered, there are specific autoantibodies, and we tend to only get them in people where there’s a clinical suspicion,” Dr. Kim said. “Within that very specific context, we kind of understand what that value means, but if you give it to the general public, then those numbers aren’t as applicable and most likely overestimate the risk of disease.”

Even if providers consider the results of a DTC test in their differential, they may want to be sure it’s from a trustworthy source. “If a provider is uncertain about whether a direct-to-consumer testing company is reputable or about whether a direct-to-consumer test result is reliable, I would encourage them to consult with their laboratory medicine colleagues,” Dr. Killeen said.
 

Responding to Patients

Like any other patient coming to a clinical visit, the most common reason patients are likely ordering these tests is that they’re seeking answers. Kim doesn’t typically see patients doing their own monitoring for diagnosed conditions between visits — the expense would add up too quickly — or testing for genetic markers, which likely wouldn’t be very helpful either.

“Even though most of our diseases probably have a genetic underpinning, how much it contributes is always unclear,” Dr. Kim said. Even conditions with clear genetic variants, such as familial Mediterranean fever, spondyloarthritis, and Behçet disease, can only support a diagnosis, not diagnose it on its own, Dr. Killeen said. And these are not among the tests currently available on most DTC company sites.

While there are also tests that can offer information about genetic risks for certain medications, such as a thiopurine methyltransferase test to find out if a patient lacks the enzyme needed to break down the immunosuppressant drug azathioprine, Kim hasn’t seen patients seeking these out either.

“The more global and more compassionate way to think about this is that we have a lot of people who are struggling to understand what’s going on with their bodies, and most physicians really don’t know what the next steps are for these people,” Dr. Kim said. “They’re desperate, and their quality of life is so poor that they’re going to take extreme steps to try to manage their own frustration with this condition.”

That means clinicians’ most powerful tools when patients come in with DTC test results are their listening skills.

“Empathy is the most important thing, just being able to share the patient’s frustration to the point where they had to take matters into their own hands,” Dr. Kim said. “I think a lot of rheumatologists are actually pretty comfortable being in this position.”

Additionally, doctors should know that some patients may be engaging in attempts to self-diagnose, self-treat, or otherwise self-manage their symptoms or perceived condition. “They just need to be aware and try to make sure there’s no harm being done,” Dr. Kim said.

Ms. Welsh didn’t seek treatment or diagnosis on her own, but getting her test also did not give her the control she was seeking. “Looking back, it was kind of a waste of money, but it felt good in the moment,” Ms. Welsh said. “I was so upset, and I wanted that control, and in the end, it didn’t get me results any sooner, and it didn’t give me peace of mind.”

It was Ms. Welsh’s primary care doctor listening to her concerns, ordering the same test she had ordered with several others, and working with her to seek answers that reassured her that her provider cared about her well-being.

“A lot of what I do in my business is reassure people that you know what they have is treatable or not going to end their life as they know it,” Dr. Putman said. “And you certainly can’t reassure them if they’re not in your clinic yet.”

Dr. Putman has participated in clinical trials with AbbVie, consulting with Novartis and GSK, and clinical trials and consulting with Amgen and AstraZeneca. Dr. Niewold reported receiving research grants from EMD Serono and Zenas BioPharma and consulting for Thermo Fisher Scientific, Progentec Diagnostics, Roivant Sciences, AstraZeneca, S3 Connected Health, Flagship Pioneering, and Guidepoint. Dr. Kim reported sponsored research agreements with AstraZeneca, Bristol-Myers Squibb, Novartis, and CRISPR Therapeutics; royalties from Kypha; and consulting/speaking for Amgen, ANI Pharmaceuticals, Atara Biotherapeutics, Aurinia Pharmaceuticals, CARGO Therapeutics, Exagen Diagnostics, GSK, Hinge Bio, Kypha, Progentec Diagnostics, Synthekine, and UpToDate. Dr. Killeen had no relevant financial relationships to disclose.
 

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

When Jennifer Welsh, a 40-year-old from New Britain, Connecticut, visited her doctor about pain in her joints and neck, her doctor sent her to the emergency department (ED) to rule out meningitis. The ED did rule that out, as well as strep, so Ms. Welsh went to her follow-up appointment a few days later, hoping for answers or at least more tests to get those answers.

Instead, the doctor — a different one from the same practice as her primary care physician (PCP) — wouldn’t even talk to Ms. Welsh about her symptoms because she couldn’t see the ED’s results and refused to view the results that Ms. Welsh could pull up online.

“She just completely shut me down,” Ms. Welsh recalled. “It was a really awful appointment, and I left in tears. I was in physical pain, I had just been to the ER, nothing is really resolved, I’m stressed out about it, and this woman is completely dismissing me.”

She had been able to schedule an appointment with her regular PCP later that week, but after the harrowing experience with this doctor, she wondered if her PCP would order the rheumatoid arthritis (RA) test that Ms. Welsh suspected she needed. So, she took matters into her own hands.

“I was searching for what test to ask for from my doctor,” she said, and she found that she could order it on her own from a major lab company she was already familiar with. For around $100, “I could get it done and see what it says on my own,” she said.

But that’s not how it worked out. Her regular PCP apologized for the other doctor’s behavior and ordered the RA test as well as additional tests — and got results while Ms. Welsh still waited for the one she ordered to arrive over a week later.

At first, Ms. Welsh was grateful she could order the RA test without her doctor’s referral. “I felt it gave me a sense of control over the situation that I felt really not in control of, until the system failed me, and I didn’t get the results,” she said. But then, “not having someone I could call and get an answer about why my tests were delayed, why I wasn’t able to access them, why it was taking so long — it was definitely anxiety-inducing.”
 

A Growing Market

Ms. Welsh is one of a growing number of patients who are ordering direct-to-consumer (DTC) lab tests without the recommendation or guidance of a doctor. They’re offered online by labs ranging from well-established giants like Quest and Labcorp to smaller, potentially less vetted companies, although some smaller companies contract with larger companies like Quest. Combined, the DTC market is projected to be worth $2 billion by 2025.

Yet the burgeoning industry has also drawn critiques from both bioethicists and privacy experts. A research letter in JAMA in 2023, for example, found that less than half of the 21 companies identified in an online search declared Health Insurance Portability and Accountability Act compliance, while more than half “indicated the potential use of consumer data for research purposes either internally or through third-party sharing.” That study found the most commonly offered tests were related to diabetes, the thyroid, and vitamin levels, and hormone tests for men and women, such as testosterone or estradiol.

But a number of companies also offer tests related to rheumatologic conditions. A handful of tests offered by Labcorp, for example, could be used in rheumatology, such as tests for celiac antibodies or high-sensitivity C-reactive protein. Quest similarly offers a handful of autoimmune-related tests. But other companies offer a long slate of autoimmune or antibody tests.

The antinuclear antibody (ANA) test and RA panel offered by Quest are the same tests, run and analyzed in the same labs, as those ordered by physicians and hospitals, according to James Faix, MD, the medical director of immunology at Quest Diagnostics. Their RA panel includes rheumatoid factor and anti-cyclic citrullinated peptide as well as antibody to mutated citrullinated vimentin, “which may detect approximately 10%-15%” of patients who test negative to the first two.

Quest’s ANA test with reflex costs $112, and its RA panel costs $110, price points that are similar across other companies’ offerings. Labcorp declined to respond to questions about its DTC tests, and several smaller companies did not respond to queries about their offerings. It can therefore be hard to assess what’s included or what the quality is of many DTC tests, particularly from smaller, less established companies.
 

Oversight and Quality Control

Anthony Killeen, MD, PhD, president of the Association for Diagnostics & Laboratory Medicine (ADLM) and director of Clinical Laboratories at the University of Minnesota Medical Center in Minneapolis, said via email that the ADLM supports “expanding consumer access to direct-to-consumer laboratory testing services that have demonstrated analytical and clinical validity and clinical utility,” given the importance of individuals learning about their health status and becoming more involved in health decisions. But the ADLM also recommends “that only CLIA-certified laboratories perform direct-to-consumer testing,” he said.

Association for Diagnostics &amp; Laboratory Medicine

“There are direct-to-consumer tests on the market that are not medical-grade laboratory tests and that may be performed in nonaccredited laboratories,” Dr. Killeen said. “We advise consumers to steer clear of such tests.” The ADLM also encourages consumers to “work with qualified healthcare providers when making decisions based off the results they receive from any direct-to-consumer tests” and recommends that DTC test companies “provide consumers with sufficient information and/or access to expert help to assist them in ordering tests and interpreting the results.”

Yet it’s unclear how much support, if any, consumers can receive in terms of understanding what their tests mean. Most of the companies in the 2023 study offered optional follow-up with a healthcare professional, but these professionals ranged from physicians to “health coaches,” and all the companies had disclaimers that “test results did not constitute medical advice.”

At Quest, the only company to respond to this news organization’s request for comment, consumer-initiated tests ordered online are first reviewed by a physician at PWNHealth, an independent, third-party physician network, to determine that it’s appropriate before the lab order is actually placed.

“Once results are available, individuals have the option to discuss their results with an independent physician at no extra cost,” Dr. Faix said. ANA or RA results outside the normal ranges may trigger a “call from a PWNHealth healthcare coordinator, who can help provide information, suggestions on next steps, and set up time for the individual to speak with an independent physician to discuss questions or concerns regarding the results,” he said.

“Our goal is not to replace the role of a healthcare provider,” Dr. Faix said. “We are providing an alternate way for people to engage with the healthcare system that offers convenience, gives people more control over their own healthcare journeys, and meets them where they are, supporting both consumers and their care teams.” The company has expanded its offerings from an initial 30 tests made available in 2018 to over 130 today, deciding which to offer “based on consumer research and expertise of clinical experts.” The company has also “seen steady interest in our two consumer rheumatology offerings,” Dr. Faix said.
 

The DTC Landscape in Rheumatology

Within rheumatology, among the most popular tests is for ANA, based on the experience of Alfred Kim, MD, PhD, associate professor of medicine at Washington University School of Medicine in St Louis, Missouri.

Dr. Kim

“For a lot of people, losing control over their health is maybe the most frightening experience they can have, so I think a lot of patients use this as a way to kind of have ownership over their health,” Dr. Kim said. “Let’s say they’ve been to four doctors. No one can explain what’s going on. They’re getting frustrated, and so they just turn to solutions where they feel like they have ownership over the situation.”

Though the market is undoubtedly growing, the growth appears uneven across geography and institution types. Kim has seen a “fair number of referrals,” with patients coming in with results from a DTC test. Michael Putman, MD, MSci, assistant professor of medicine at the Medical College of Wisconsin in Milwaukee, hasn’t seen it much. “I know that patients can get testing done themselves independently, but I don’t have people routinely coming in with tests they’ve ordered in advance of our appointment,” Dr. Putman said, but, like Dr. Kim, he recognizes why patients might seek them out.

Dr. Putman

Ron Hester Photography

Risks vs Benefits

DTC testing is not an answer to the national shortage of rheumatologists, however, especially given the risks that Dr. Niewold, Dr. Putman, and Dr. Kim worry outweigh potential benefits. On the one hand, getting online test results may help expedite a referral to a specialist, Dr. Niewold said. But a long wait for that appointment could then easily become a bigger source of anxiety than comfort, Dr. Putman said.

“It’s a trade-off where you are accepting a lot more people getting false-positive diagnoses and spending months thinking they have some disease where they might not, in exchange for a couple people who would have had a delayed diagnosis,” Dr. Putman said. “There’s an enormous amount of existential suffering,” that’s familiar to rheumatologists because some patients may dread the diagnosis of a rheumatic disease the way they might fear a cancer diagnosis, especially if they have lost a family member to a condition that they suspect they share, he said. “To put yourself into an existential catastrophe — that’s not a small harm.”

Dr. Niewold agreed, pointing out that patients with a positive ANA test may “get unnecessarily worried and stay up all night reading about lupus, getting scared for weeks on end before seeing a specialist.” And there are financial harms as well for patients who may order the same test multiple times, or a whole slate of tests, that they don’t need for hundreds or thousands of dollars. There’s also the lost time and effort of researching a condition or even seeking out support groups that patients may pursue, Dr. Niewold said.

The likely biggest risk to individuals, however, is the potential for overdiagnosis or misdiagnosis.

“If someone comes in and they’ve read the textbook on lupus and they have a positive ANA, it’s really hard as a rheumatologist to walk that back,” Dr. Putman said. “The human mind is a powerful thing,” he added, and people who get a positive test will likely start to notice things like joint pain or a rash on their cheeks and begin attributing it to a diagnosis they risk convincing themselves they have. “When people come into your clinic not knowing what a disease would look like and they just tell you how they’re feeling, it’s a much cleaner and more honest way to approach diagnosis.”

Most patients likely don’t realize, for example, that none of the tests rheumatologists usually order are diagnostic in and of themselves, Dr. Niewold said. “They’re all kind of like stars in the constellation of a diagnosis,” he said. “They’re helpful, but none of them is sufficient by itself.”

Dr. Killeen agreed, noting that “consumers might not understand the nuances of these tests well enough to know whether it is appropriate to order them or how to interpret the results correctly.” Given the long-term implications of a diagnosis for a rheumatologic disease, “I would have concerns about consumers ordering and interpreting rheumatologic tests without working closely with their physicians,” Dr. Killeen said. “The main concern that lab experts have about direct-to-consumer tests is the potential for people to get misleading results and/or to misinterpret their results, which in turn could lead to people not getting the treatment they need or getting treatment when they don’t need any at all.”

It’s one thing for patients to come in asking for a particular treatment they may not need but which a doctor may be able to dissuade them from seeking. But Dr. Kim also pointed out the risk that patients may decide to treat themselves with therapies that haven’t undergone rigorous testing or haven’t been recommended by a physician.

“We tend to have people who come in with a pretty clear idea of what they want done, but the problem is, we don’t know if their reasoning is correct from a clinical perspective,” Dr. Kim said. Companies offer these tests with the belief that they’re “providing patients a choice, an option to take ownership,” he said, “but the potential harm can be realized very quickly because there are going to be people who are misdiagnosing themselves and, worse yet, may then pursue their own treatment plan that’s going in the opposite direction of where we think it needs to go.”

Or, on the flip side, if a patient erroneously believes they have the answer to what ails them, it may delay diagnosis of a more serious condition that’s rarer or harder to detect. Kim pointed to, for example, intravascular lymphoma, which is notoriously as difficult to identify as it is rare and aggressive. If a patient’s confirmation bias has led them to believe they have an autoimmune condition, they may not receive the more serious diagnosis until it’s advanced too far to treat.
 

Patient-Provider Relationship Friction

Another concern is how these tests may lead to confusion and frustration that can erode the patient-provider relationship, particularly because most patients don’t know how to interpret the results or understand the bigger context in which the results have to be interpreted. Many patients may think a test can come back with a binary answer, a positive or negative, and that means they do or don’t have a condition. That’s generally true for pregnancy tests, COVID tests, and sexually transmitted infection tests — the kinds of tests that have long been available to consumers and which have fairly straightforward answers.

But physicians know that’s not the case for many conditions, particularly those in rheumatology.

“In rheumatic diseases, because the tests have such marginal value in terms of diagnosis, almost always we develop a suspicion before we even think about ordering the tests, and then that dictates whether or not we cross that threshold,” Dr. Kim said. “A negative test doesn’t exclude the fact that you may have disease X, but a positive test also doesn’t mean you have disease X. All they provide is an idea of the risk.”

But some patients who come in with DTC test results have “already made the decision in their mind that they have a certain condition,” Dr. Kim said. “This is obviously dangerous because the majority of these patients do not have the condition they think they have, and it leaves a very uncomfortable feeling after the visit because they feel like they’ve been either betrayed by me or by the test, and they leave more confused.”

Patients may also come in with tests that a doctor isn’t familiar with or isn’t sure how to interpret on its own, at least for that particular patient.

“For ANA testing, we have a pretty good idea of its positive and negative predictive value because it’s ordered so much, but for many of these tests being offered, there are specific autoantibodies, and we tend to only get them in people where there’s a clinical suspicion,” Dr. Kim said. “Within that very specific context, we kind of understand what that value means, but if you give it to the general public, then those numbers aren’t as applicable and most likely overestimate the risk of disease.”

Even if providers consider the results of a DTC test in their differential, they may want to be sure it’s from a trustworthy source. “If a provider is uncertain about whether a direct-to-consumer testing company is reputable or about whether a direct-to-consumer test result is reliable, I would encourage them to consult with their laboratory medicine colleagues,” Dr. Killeen said.
 

Responding to Patients

Like any other patient coming to a clinical visit, the most common reason patients are likely ordering these tests is that they’re seeking answers. Kim doesn’t typically see patients doing their own monitoring for diagnosed conditions between visits — the expense would add up too quickly — or testing for genetic markers, which likely wouldn’t be very helpful either.

“Even though most of our diseases probably have a genetic underpinning, how much it contributes is always unclear,” Dr. Kim said. Even conditions with clear genetic variants, such as familial Mediterranean fever, spondyloarthritis, and Behçet disease, can only support a diagnosis, not diagnose it on its own, Dr. Killeen said. And these are not among the tests currently available on most DTC company sites.

While there are also tests that can offer information about genetic risks for certain medications, such as a thiopurine methyltransferase test to find out if a patient lacks the enzyme needed to break down the immunosuppressant drug azathioprine, Kim hasn’t seen patients seeking these out either.

“The more global and more compassionate way to think about this is that we have a lot of people who are struggling to understand what’s going on with their bodies, and most physicians really don’t know what the next steps are for these people,” Dr. Kim said. “They’re desperate, and their quality of life is so poor that they’re going to take extreme steps to try to manage their own frustration with this condition.”

That means clinicians’ most powerful tools when patients come in with DTC test results are their listening skills.

“Empathy is the most important thing, just being able to share the patient’s frustration to the point where they had to take matters into their own hands,” Dr. Kim said. “I think a lot of rheumatologists are actually pretty comfortable being in this position.”

Additionally, doctors should know that some patients may be engaging in attempts to self-diagnose, self-treat, or otherwise self-manage their symptoms or perceived condition. “They just need to be aware and try to make sure there’s no harm being done,” Dr. Kim said.

Ms. Welsh didn’t seek treatment or diagnosis on her own, but getting her test also did not give her the control she was seeking. “Looking back, it was kind of a waste of money, but it felt good in the moment,” Ms. Welsh said. “I was so upset, and I wanted that control, and in the end, it didn’t get me results any sooner, and it didn’t give me peace of mind.”

It was Ms. Welsh’s primary care doctor listening to her concerns, ordering the same test she had ordered with several others, and working with her to seek answers that reassured her that her provider cared about her well-being.

“A lot of what I do in my business is reassure people that you know what they have is treatable or not going to end their life as they know it,” Dr. Putman said. “And you certainly can’t reassure them if they’re not in your clinic yet.”

Dr. Putman has participated in clinical trials with AbbVie, consulting with Novartis and GSK, and clinical trials and consulting with Amgen and AstraZeneca. Dr. Niewold reported receiving research grants from EMD Serono and Zenas BioPharma and consulting for Thermo Fisher Scientific, Progentec Diagnostics, Roivant Sciences, AstraZeneca, S3 Connected Health, Flagship Pioneering, and Guidepoint. Dr. Kim reported sponsored research agreements with AstraZeneca, Bristol-Myers Squibb, Novartis, and CRISPR Therapeutics; royalties from Kypha; and consulting/speaking for Amgen, ANI Pharmaceuticals, Atara Biotherapeutics, Aurinia Pharmaceuticals, CARGO Therapeutics, Exagen Diagnostics, GSK, Hinge Bio, Kypha, Progentec Diagnostics, Synthekine, and UpToDate. Dr. Killeen had no relevant financial relationships to disclose.
 

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

When Jennifer Welsh, a 40-year-old from New Britain, Connecticut, visited her doctor about pain in her joints and neck, her doctor sent her to the emergency department (ED) to rule out meningitis. The ED did rule that out, as well as strep, so Ms. Welsh went to her follow-up appointment a few days later, hoping for answers or at least more tests to get those answers.

Instead, the doctor — a different one from the same practice as her primary care physician (PCP) — wouldn’t even talk to Ms. Welsh about her symptoms because she couldn’t see the ED’s results and refused to view the results that Ms. Welsh could pull up online.

“She just completely shut me down,” Ms. Welsh recalled. “It was a really awful appointment, and I left in tears. I was in physical pain, I had just been to the ER, nothing is really resolved, I’m stressed out about it, and this woman is completely dismissing me.”

She had been able to schedule an appointment with her regular PCP later that week, but after the harrowing experience with this doctor, she wondered if her PCP would order the rheumatoid arthritis (RA) test that Ms. Welsh suspected she needed. So, she took matters into her own hands.

“I was searching for what test to ask for from my doctor,” she said, and she found that she could order it on her own from a major lab company she was already familiar with. For around $100, “I could get it done and see what it says on my own,” she said.

But that’s not how it worked out. Her regular PCP apologized for the other doctor’s behavior and ordered the RA test as well as additional tests — and got results while Ms. Welsh still waited for the one she ordered to arrive over a week later.

At first, Ms. Welsh was grateful she could order the RA test without her doctor’s referral. “I felt it gave me a sense of control over the situation that I felt really not in control of, until the system failed me, and I didn’t get the results,” she said. But then, “not having someone I could call and get an answer about why my tests were delayed, why I wasn’t able to access them, why it was taking so long — it was definitely anxiety-inducing.”
 

A Growing Market

Ms. Welsh is one of a growing number of patients who are ordering direct-to-consumer (DTC) lab tests without the recommendation or guidance of a doctor. They’re offered online by labs ranging from well-established giants like Quest and Labcorp to smaller, potentially less vetted companies, although some smaller companies contract with larger companies like Quest. Combined, the DTC market is projected to be worth $2 billion by 2025.

Yet the burgeoning industry has also drawn critiques from both bioethicists and privacy experts. A research letter in JAMA in 2023, for example, found that less than half of the 21 companies identified in an online search declared Health Insurance Portability and Accountability Act compliance, while more than half “indicated the potential use of consumer data for research purposes either internally or through third-party sharing.” That study found the most commonly offered tests were related to diabetes, the thyroid, and vitamin levels, and hormone tests for men and women, such as testosterone or estradiol.

But a number of companies also offer tests related to rheumatologic conditions. A handful of tests offered by Labcorp, for example, could be used in rheumatology, such as tests for celiac antibodies or high-sensitivity C-reactive protein. Quest similarly offers a handful of autoimmune-related tests. But other companies offer a long slate of autoimmune or antibody tests.

The antinuclear antibody (ANA) test and RA panel offered by Quest are the same tests, run and analyzed in the same labs, as those ordered by physicians and hospitals, according to James Faix, MD, the medical director of immunology at Quest Diagnostics. Their RA panel includes rheumatoid factor and anti-cyclic citrullinated peptide as well as antibody to mutated citrullinated vimentin, “which may detect approximately 10%-15%” of patients who test negative to the first two.

Quest’s ANA test with reflex costs $112, and its RA panel costs $110, price points that are similar across other companies’ offerings. Labcorp declined to respond to questions about its DTC tests, and several smaller companies did not respond to queries about their offerings. It can therefore be hard to assess what’s included or what the quality is of many DTC tests, particularly from smaller, less established companies.
 

Oversight and Quality Control

Anthony Killeen, MD, PhD, president of the Association for Diagnostics & Laboratory Medicine (ADLM) and director of Clinical Laboratories at the University of Minnesota Medical Center in Minneapolis, said via email that the ADLM supports “expanding consumer access to direct-to-consumer laboratory testing services that have demonstrated analytical and clinical validity and clinical utility,” given the importance of individuals learning about their health status and becoming more involved in health decisions. But the ADLM also recommends “that only CLIA-certified laboratories perform direct-to-consumer testing,” he said.

Association for Diagnostics &amp; Laboratory Medicine

“There are direct-to-consumer tests on the market that are not medical-grade laboratory tests and that may be performed in nonaccredited laboratories,” Dr. Killeen said. “We advise consumers to steer clear of such tests.” The ADLM also encourages consumers to “work with qualified healthcare providers when making decisions based off the results they receive from any direct-to-consumer tests” and recommends that DTC test companies “provide consumers with sufficient information and/or access to expert help to assist them in ordering tests and interpreting the results.”

Yet it’s unclear how much support, if any, consumers can receive in terms of understanding what their tests mean. Most of the companies in the 2023 study offered optional follow-up with a healthcare professional, but these professionals ranged from physicians to “health coaches,” and all the companies had disclaimers that “test results did not constitute medical advice.”

At Quest, the only company to respond to this news organization’s request for comment, consumer-initiated tests ordered online are first reviewed by a physician at PWNHealth, an independent, third-party physician network, to determine that it’s appropriate before the lab order is actually placed.

“Once results are available, individuals have the option to discuss their results with an independent physician at no extra cost,” Dr. Faix said. ANA or RA results outside the normal ranges may trigger a “call from a PWNHealth healthcare coordinator, who can help provide information, suggestions on next steps, and set up time for the individual to speak with an independent physician to discuss questions or concerns regarding the results,” he said.

“Our goal is not to replace the role of a healthcare provider,” Dr. Faix said. “We are providing an alternate way for people to engage with the healthcare system that offers convenience, gives people more control over their own healthcare journeys, and meets them where they are, supporting both consumers and their care teams.” The company has expanded its offerings from an initial 30 tests made available in 2018 to over 130 today, deciding which to offer “based on consumer research and expertise of clinical experts.” The company has also “seen steady interest in our two consumer rheumatology offerings,” Dr. Faix said.
 

The DTC Landscape in Rheumatology

Within rheumatology, among the most popular tests is for ANA, based on the experience of Alfred Kim, MD, PhD, associate professor of medicine at Washington University School of Medicine in St Louis, Missouri.

Dr. Kim

“For a lot of people, losing control over their health is maybe the most frightening experience they can have, so I think a lot of patients use this as a way to kind of have ownership over their health,” Dr. Kim said. “Let’s say they’ve been to four doctors. No one can explain what’s going on. They’re getting frustrated, and so they just turn to solutions where they feel like they have ownership over the situation.”

Though the market is undoubtedly growing, the growth appears uneven across geography and institution types. Kim has seen a “fair number of referrals,” with patients coming in with results from a DTC test. Michael Putman, MD, MSci, assistant professor of medicine at the Medical College of Wisconsin in Milwaukee, hasn’t seen it much. “I know that patients can get testing done themselves independently, but I don’t have people routinely coming in with tests they’ve ordered in advance of our appointment,” Dr. Putman said, but, like Dr. Kim, he recognizes why patients might seek them out.

Dr. Putman

Ron Hester Photography

Risks vs Benefits

DTC testing is not an answer to the national shortage of rheumatologists, however, especially given the risks that Dr. Niewold, Dr. Putman, and Dr. Kim worry outweigh potential benefits. On the one hand, getting online test results may help expedite a referral to a specialist, Dr. Niewold said. But a long wait for that appointment could then easily become a bigger source of anxiety than comfort, Dr. Putman said.

“It’s a trade-off where you are accepting a lot more people getting false-positive diagnoses and spending months thinking they have some disease where they might not, in exchange for a couple people who would have had a delayed diagnosis,” Dr. Putman said. “There’s an enormous amount of existential suffering,” that’s familiar to rheumatologists because some patients may dread the diagnosis of a rheumatic disease the way they might fear a cancer diagnosis, especially if they have lost a family member to a condition that they suspect they share, he said. “To put yourself into an existential catastrophe — that’s not a small harm.”

Dr. Niewold agreed, pointing out that patients with a positive ANA test may “get unnecessarily worried and stay up all night reading about lupus, getting scared for weeks on end before seeing a specialist.” And there are financial harms as well for patients who may order the same test multiple times, or a whole slate of tests, that they don’t need for hundreds or thousands of dollars. There’s also the lost time and effort of researching a condition or even seeking out support groups that patients may pursue, Dr. Niewold said.

The likely biggest risk to individuals, however, is the potential for overdiagnosis or misdiagnosis.

“If someone comes in and they’ve read the textbook on lupus and they have a positive ANA, it’s really hard as a rheumatologist to walk that back,” Dr. Putman said. “The human mind is a powerful thing,” he added, and people who get a positive test will likely start to notice things like joint pain or a rash on their cheeks and begin attributing it to a diagnosis they risk convincing themselves they have. “When people come into your clinic not knowing what a disease would look like and they just tell you how they’re feeling, it’s a much cleaner and more honest way to approach diagnosis.”

Most patients likely don’t realize, for example, that none of the tests rheumatologists usually order are diagnostic in and of themselves, Dr. Niewold said. “They’re all kind of like stars in the constellation of a diagnosis,” he said. “They’re helpful, but none of them is sufficient by itself.”

Dr. Killeen agreed, noting that “consumers might not understand the nuances of these tests well enough to know whether it is appropriate to order them or how to interpret the results correctly.” Given the long-term implications of a diagnosis for a rheumatologic disease, “I would have concerns about consumers ordering and interpreting rheumatologic tests without working closely with their physicians,” Dr. Killeen said. “The main concern that lab experts have about direct-to-consumer tests is the potential for people to get misleading results and/or to misinterpret their results, which in turn could lead to people not getting the treatment they need or getting treatment when they don’t need any at all.”

It’s one thing for patients to come in asking for a particular treatment they may not need but which a doctor may be able to dissuade them from seeking. But Dr. Kim also pointed out the risk that patients may decide to treat themselves with therapies that haven’t undergone rigorous testing or haven’t been recommended by a physician.

“We tend to have people who come in with a pretty clear idea of what they want done, but the problem is, we don’t know if their reasoning is correct from a clinical perspective,” Dr. Kim said. Companies offer these tests with the belief that they’re “providing patients a choice, an option to take ownership,” he said, “but the potential harm can be realized very quickly because there are going to be people who are misdiagnosing themselves and, worse yet, may then pursue their own treatment plan that’s going in the opposite direction of where we think it needs to go.”

Or, on the flip side, if a patient erroneously believes they have the answer to what ails them, it may delay diagnosis of a more serious condition that’s rarer or harder to detect. Kim pointed to, for example, intravascular lymphoma, which is notoriously as difficult to identify as it is rare and aggressive. If a patient’s confirmation bias has led them to believe they have an autoimmune condition, they may not receive the more serious diagnosis until it’s advanced too far to treat.
 

Patient-Provider Relationship Friction

Another concern is how these tests may lead to confusion and frustration that can erode the patient-provider relationship, particularly because most patients don’t know how to interpret the results or understand the bigger context in which the results have to be interpreted. Many patients may think a test can come back with a binary answer, a positive or negative, and that means they do or don’t have a condition. That’s generally true for pregnancy tests, COVID tests, and sexually transmitted infection tests — the kinds of tests that have long been available to consumers and which have fairly straightforward answers.

But physicians know that’s not the case for many conditions, particularly those in rheumatology.

“In rheumatic diseases, because the tests have such marginal value in terms of diagnosis, almost always we develop a suspicion before we even think about ordering the tests, and then that dictates whether or not we cross that threshold,” Dr. Kim said. “A negative test doesn’t exclude the fact that you may have disease X, but a positive test also doesn’t mean you have disease X. All they provide is an idea of the risk.”

But some patients who come in with DTC test results have “already made the decision in their mind that they have a certain condition,” Dr. Kim said. “This is obviously dangerous because the majority of these patients do not have the condition they think they have, and it leaves a very uncomfortable feeling after the visit because they feel like they’ve been either betrayed by me or by the test, and they leave more confused.”

Patients may also come in with tests that a doctor isn’t familiar with or isn’t sure how to interpret on its own, at least for that particular patient.

“For ANA testing, we have a pretty good idea of its positive and negative predictive value because it’s ordered so much, but for many of these tests being offered, there are specific autoantibodies, and we tend to only get them in people where there’s a clinical suspicion,” Dr. Kim said. “Within that very specific context, we kind of understand what that value means, but if you give it to the general public, then those numbers aren’t as applicable and most likely overestimate the risk of disease.”

Even if providers consider the results of a DTC test in their differential, they may want to be sure it’s from a trustworthy source. “If a provider is uncertain about whether a direct-to-consumer testing company is reputable or about whether a direct-to-consumer test result is reliable, I would encourage them to consult with their laboratory medicine colleagues,” Dr. Killeen said.
 

Responding to Patients

Like any other patient coming to a clinical visit, the most common reason patients are likely ordering these tests is that they’re seeking answers. Kim doesn’t typically see patients doing their own monitoring for diagnosed conditions between visits — the expense would add up too quickly — or testing for genetic markers, which likely wouldn’t be very helpful either.

“Even though most of our diseases probably have a genetic underpinning, how much it contributes is always unclear,” Dr. Kim said. Even conditions with clear genetic variants, such as familial Mediterranean fever, spondyloarthritis, and Behçet disease, can only support a diagnosis, not diagnose it on its own, Dr. Killeen said. And these are not among the tests currently available on most DTC company sites.

While there are also tests that can offer information about genetic risks for certain medications, such as a thiopurine methyltransferase test to find out if a patient lacks the enzyme needed to break down the immunosuppressant drug azathioprine, Kim hasn’t seen patients seeking these out either.

“The more global and more compassionate way to think about this is that we have a lot of people who are struggling to understand what’s going on with their bodies, and most physicians really don’t know what the next steps are for these people,” Dr. Kim said. “They’re desperate, and their quality of life is so poor that they’re going to take extreme steps to try to manage their own frustration with this condition.”

That means clinicians’ most powerful tools when patients come in with DTC test results are their listening skills.

“Empathy is the most important thing, just being able to share the patient’s frustration to the point where they had to take matters into their own hands,” Dr. Kim said. “I think a lot of rheumatologists are actually pretty comfortable being in this position.”

Additionally, doctors should know that some patients may be engaging in attempts to self-diagnose, self-treat, or otherwise self-manage their symptoms or perceived condition. “They just need to be aware and try to make sure there’s no harm being done,” Dr. Kim said.

Ms. Welsh didn’t seek treatment or diagnosis on her own, but getting her test also did not give her the control she was seeking. “Looking back, it was kind of a waste of money, but it felt good in the moment,” Ms. Welsh said. “I was so upset, and I wanted that control, and in the end, it didn’t get me results any sooner, and it didn’t give me peace of mind.”

It was Ms. Welsh’s primary care doctor listening to her concerns, ordering the same test she had ordered with several others, and working with her to seek answers that reassured her that her provider cared about her well-being.

“A lot of what I do in my business is reassure people that you know what they have is treatable or not going to end their life as they know it,” Dr. Putman said. “And you certainly can’t reassure them if they’re not in your clinic yet.”

Dr. Putman has participated in clinical trials with AbbVie, consulting with Novartis and GSK, and clinical trials and consulting with Amgen and AstraZeneca. Dr. Niewold reported receiving research grants from EMD Serono and Zenas BioPharma and consulting for Thermo Fisher Scientific, Progentec Diagnostics, Roivant Sciences, AstraZeneca, S3 Connected Health, Flagship Pioneering, and Guidepoint. Dr. Kim reported sponsored research agreements with AstraZeneca, Bristol-Myers Squibb, Novartis, and CRISPR Therapeutics; royalties from Kypha; and consulting/speaking for Amgen, ANI Pharmaceuticals, Atara Biotherapeutics, Aurinia Pharmaceuticals, CARGO Therapeutics, Exagen Diagnostics, GSK, Hinge Bio, Kypha, Progentec Diagnostics, Synthekine, and UpToDate. Dr. Killeen had no relevant financial relationships to disclose.
 

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

Two relatively simple interventions — addressing high blood pressure (BP) and smoking cessation — could make a huge difference for patients with rheumatic disease. Patients with autoimmune disease are up to three times more likely to develop cardiovascular disease (CVD) than the general population. In addition to compounding CVD, smoking is tied to the development of certain autoimmune conditions, as well as worse outcomes. Christie Bartels, MD, chief of the Division of Rheumatology at the University of Wisconsin School of Medicine and Public Health, Madison, has focused her research on improving cardiac health in inflammatory diseases. This news organization spoke with Bartels about two short interventions she developed that tackle hypertension and smoking cessation during regular visits, each taking less than 3 minutes.

How Do These Programs Address Cardiac Disease Prevention?

The BP and Quit Connect programs help clinics systematically address the two most modifiable risk factors for CVD: high BP and smoking. There’s also evidence that addressing these two risk factors improves outcomes in rheumatic diseases. Hypertension predicts an increase in lupus damage. Particularly in lupus nephritis, hypertension will increase the risk for CVD and kidney failure. People who use tobacco have worse outcomes in diseases like rheumatoid arthritis, psoriatic arthritis, and lupus, as well as more CVD, and antirheumatic drugs may not work as well.

University of Wisconsin School of Medicine and Public Health

In 90 seconds to 3 minutes, staff can do protocol-based care, which we’ve done across 20,000-plus visits. We showed we can improve population level rates of high BP and BP control, as well as increase smoking quitting rates across different patient settings.
 

What Is the Quit Connect Program?

The Quit Connect program is a 10- to 90-second point of care intervention. During rooming, staff (medical assistants and nurses) ask patients: “A) Do you smoke? and B) Have you thought about cutting back or quitting in the next 30 days?”

It turns out, when you ask the question that way, between a third and a half of people say that they’ve thought about cutting back or quitting. Then, we can get patients connected directly to Quitline, a free public service across all 50 states that smokers can use to get cessation support.

If patients are ready, we ask if we can arrange for them to receive a call from a Quitline coach about setting a quit date or receiving free nicotine replacement therapy. The beautiful thing is when that all happens, A) it’s free to the patient, and B) the results from the Quitline can be recorded right back to the electronic health record.

In our most recent publication in Arthritis Care & Research, we documented bringing Quit Connect to Grady Hospital in downtown Atlanta. It’s a safety net hospital, where 80% patients are Black and 70%-80% patients are on public insurance or uninsured. Using this protocol, we improved Quitline referrals 20-fold.
 

What Is the BP Connect Program?

At least half of the encounters in United States happen in specialty clinics. Unfortunately, when patients get their BP measured in a specialty clinic that’s not a cardiology or a vascular clinic, often, even if the pressure is high, the clinic doesn’t give patients feedback on that. The problem is because we haven’t said anything, that gives people the false reassurance that their BP is okay.

We’ve developed a 3-minute protocol to ask, advise, and connect. The idea is that if we measure a high BP, then we remeasure and confirm that it’s high. Then, we advise why it matters in rheumatic disease: Patients with rheumatic diseases are already at an increased risk for heart disease, and controlling BP can make a big difference. Then, we connect patients with high BP back to primary care.

Specifically, a SmartSet — an electronic medical record feature — prompts different actions based on confirmed high BP readings:

• If systolic BP ≥ 140-159, the SmartSet directs scheduling a visit to a nurse or primary care provider.
• If systolic BP ≥ 160-179, the next primary care visit anticipates the need to see a prescriber.
• If systolic BP ≥ 180, then the medical assistant or nurse at the visit is instructed to notify the provider who can arrange a provider-to-provider handoff for safety to exclude a hypertensive emergency.

That order goes to the scheduler to call primary care to coordinate follow-up. BP Connect doubled the likelihood of a guideline-recommended follow-up in primary care within 30 days. All patients benefited, and disparities decreased. BP Connect has had 1100 downloads, and both BP and Quit Connect programs are endorsed by the Centers for Disease Control and Prevention and Million Hearts.
 

How Do These Programs Affect Clinical Practice?

We developed these interventions with a health system engineer, and we time stamped everything. Part of the sustainability of this model is that it fits within a regular workflow. As a practicing rheumatologist, I understand that time is a precious commodity.

The interventions are in partnership with frontline staff. We’ve received feedback that they feel pride participating in these initiatives. They can say, because of me, 30 patients followed up last month for high BP, or 10 patients took a referral to the Quitline last year. We celebrate these accomplishments with the staff.
 

What Are the Next Steps for These Programs?

Public-facing toolkits for both BP and Quit Connect programs are available online. We have implemented [these programs] in a rural setting, in an urban setting, in Milwaukee and in Atlanta, and we are looking in the future to do a larger, multistate implementation study. If folks are interested, we’d love to partner with them to look at disseminating this further.

A version of this article appeared on Medscape.com.

Two relatively simple interventions — addressing high blood pressure (BP) and smoking cessation — could make a huge difference for patients with rheumatic disease. Patients with autoimmune disease are up to three times more likely to develop cardiovascular disease (CVD) than the general population. In addition to compounding CVD, smoking is tied to the development of certain autoimmune conditions, as well as worse outcomes. Christie Bartels, MD, chief of the Division of Rheumatology at the University of Wisconsin School of Medicine and Public Health, Madison, has focused her research on improving cardiac health in inflammatory diseases. This news organization spoke with Bartels about two short interventions she developed that tackle hypertension and smoking cessation during regular visits, each taking less than 3 minutes.

How Do These Programs Address Cardiac Disease Prevention?

The BP and Quit Connect programs help clinics systematically address the two most modifiable risk factors for CVD: high BP and smoking. There’s also evidence that addressing these two risk factors improves outcomes in rheumatic diseases. Hypertension predicts an increase in lupus damage. Particularly in lupus nephritis, hypertension will increase the risk for CVD and kidney failure. People who use tobacco have worse outcomes in diseases like rheumatoid arthritis, psoriatic arthritis, and lupus, as well as more CVD, and antirheumatic drugs may not work as well.

University of Wisconsin School of Medicine and Public Health

In 90 seconds to 3 minutes, staff can do protocol-based care, which we’ve done across 20,000-plus visits. We showed we can improve population level rates of high BP and BP control, as well as increase smoking quitting rates across different patient settings.
 

What Is the Quit Connect Program?

The Quit Connect program is a 10- to 90-second point of care intervention. During rooming, staff (medical assistants and nurses) ask patients: “A) Do you smoke? and B) Have you thought about cutting back or quitting in the next 30 days?”

It turns out, when you ask the question that way, between a third and a half of people say that they’ve thought about cutting back or quitting. Then, we can get patients connected directly to Quitline, a free public service across all 50 states that smokers can use to get cessation support.

If patients are ready, we ask if we can arrange for them to receive a call from a Quitline coach about setting a quit date or receiving free nicotine replacement therapy. The beautiful thing is when that all happens, A) it’s free to the patient, and B) the results from the Quitline can be recorded right back to the electronic health record.

In our most recent publication in Arthritis Care & Research, we documented bringing Quit Connect to Grady Hospital in downtown Atlanta. It’s a safety net hospital, where 80% patients are Black and 70%-80% patients are on public insurance or uninsured. Using this protocol, we improved Quitline referrals 20-fold.
 

What Is the BP Connect Program?

At least half of the encounters in United States happen in specialty clinics. Unfortunately, when patients get their BP measured in a specialty clinic that’s not a cardiology or a vascular clinic, often, even if the pressure is high, the clinic doesn’t give patients feedback on that. The problem is because we haven’t said anything, that gives people the false reassurance that their BP is okay.

We’ve developed a 3-minute protocol to ask, advise, and connect. The idea is that if we measure a high BP, then we remeasure and confirm that it’s high. Then, we advise why it matters in rheumatic disease: Patients with rheumatic diseases are already at an increased risk for heart disease, and controlling BP can make a big difference. Then, we connect patients with high BP back to primary care.

Specifically, a SmartSet — an electronic medical record feature — prompts different actions based on confirmed high BP readings:

• If systolic BP ≥ 140-159, the SmartSet directs scheduling a visit to a nurse or primary care provider.
• If systolic BP ≥ 160-179, the next primary care visit anticipates the need to see a prescriber.
• If systolic BP ≥ 180, then the medical assistant or nurse at the visit is instructed to notify the provider who can arrange a provider-to-provider handoff for safety to exclude a hypertensive emergency.

That order goes to the scheduler to call primary care to coordinate follow-up. BP Connect doubled the likelihood of a guideline-recommended follow-up in primary care within 30 days. All patients benefited, and disparities decreased. BP Connect has had 1100 downloads, and both BP and Quit Connect programs are endorsed by the Centers for Disease Control and Prevention and Million Hearts.
 

How Do These Programs Affect Clinical Practice?

We developed these interventions with a health system engineer, and we time stamped everything. Part of the sustainability of this model is that it fits within a regular workflow. As a practicing rheumatologist, I understand that time is a precious commodity.

The interventions are in partnership with frontline staff. We’ve received feedback that they feel pride participating in these initiatives. They can say, because of me, 30 patients followed up last month for high BP, or 10 patients took a referral to the Quitline last year. We celebrate these accomplishments with the staff.
 

What Are the Next Steps for These Programs?

Public-facing toolkits for both BP and Quit Connect programs are available online. We have implemented [these programs] in a rural setting, in an urban setting, in Milwaukee and in Atlanta, and we are looking in the future to do a larger, multistate implementation study. If folks are interested, we’d love to partner with them to look at disseminating this further.

A version of this article appeared on Medscape.com.

Two relatively simple interventions — addressing high blood pressure (BP) and smoking cessation — could make a huge difference for patients with rheumatic disease. Patients with autoimmune disease are up to three times more likely to develop cardiovascular disease (CVD) than the general population. In addition to compounding CVD, smoking is tied to the development of certain autoimmune conditions, as well as worse outcomes. Christie Bartels, MD, chief of the Division of Rheumatology at the University of Wisconsin School of Medicine and Public Health, Madison, has focused her research on improving cardiac health in inflammatory diseases. This news organization spoke with Bartels about two short interventions she developed that tackle hypertension and smoking cessation during regular visits, each taking less than 3 minutes.

How Do These Programs Address Cardiac Disease Prevention?

The BP and Quit Connect programs help clinics systematically address the two most modifiable risk factors for CVD: high BP and smoking. There’s also evidence that addressing these two risk factors improves outcomes in rheumatic diseases. Hypertension predicts an increase in lupus damage. Particularly in lupus nephritis, hypertension will increase the risk for CVD and kidney failure. People who use tobacco have worse outcomes in diseases like rheumatoid arthritis, psoriatic arthritis, and lupus, as well as more CVD, and antirheumatic drugs may not work as well.

University of Wisconsin School of Medicine and Public Health

In 90 seconds to 3 minutes, staff can do protocol-based care, which we’ve done across 20,000-plus visits. We showed we can improve population level rates of high BP and BP control, as well as increase smoking quitting rates across different patient settings.
 

What Is the Quit Connect Program?

The Quit Connect program is a 10- to 90-second point of care intervention. During rooming, staff (medical assistants and nurses) ask patients: “A) Do you smoke? and B) Have you thought about cutting back or quitting in the next 30 days?”

It turns out, when you ask the question that way, between a third and a half of people say that they’ve thought about cutting back or quitting. Then, we can get patients connected directly to Quitline, a free public service across all 50 states that smokers can use to get cessation support.

If patients are ready, we ask if we can arrange for them to receive a call from a Quitline coach about setting a quit date or receiving free nicotine replacement therapy. The beautiful thing is when that all happens, A) it’s free to the patient, and B) the results from the Quitline can be recorded right back to the electronic health record.

In our most recent publication in Arthritis Care & Research, we documented bringing Quit Connect to Grady Hospital in downtown Atlanta. It’s a safety net hospital, where 80% patients are Black and 70%-80% patients are on public insurance or uninsured. Using this protocol, we improved Quitline referrals 20-fold.
 

What Is the BP Connect Program?

At least half of the encounters in United States happen in specialty clinics. Unfortunately, when patients get their BP measured in a specialty clinic that’s not a cardiology or a vascular clinic, often, even if the pressure is high, the clinic doesn’t give patients feedback on that. The problem is because we haven’t said anything, that gives people the false reassurance that their BP is okay.

We’ve developed a 3-minute protocol to ask, advise, and connect. The idea is that if we measure a high BP, then we remeasure and confirm that it’s high. Then, we advise why it matters in rheumatic disease: Patients with rheumatic diseases are already at an increased risk for heart disease, and controlling BP can make a big difference. Then, we connect patients with high BP back to primary care.

Specifically, a SmartSet — an electronic medical record feature — prompts different actions based on confirmed high BP readings:

• If systolic BP ≥ 140-159, the SmartSet directs scheduling a visit to a nurse or primary care provider.
• If systolic BP ≥ 160-179, the next primary care visit anticipates the need to see a prescriber.
• If systolic BP ≥ 180, then the medical assistant or nurse at the visit is instructed to notify the provider who can arrange a provider-to-provider handoff for safety to exclude a hypertensive emergency.

That order goes to the scheduler to call primary care to coordinate follow-up. BP Connect doubled the likelihood of a guideline-recommended follow-up in primary care within 30 days. All patients benefited, and disparities decreased. BP Connect has had 1100 downloads, and both BP and Quit Connect programs are endorsed by the Centers for Disease Control and Prevention and Million Hearts.
 

How Do These Programs Affect Clinical Practice?

We developed these interventions with a health system engineer, and we time stamped everything. Part of the sustainability of this model is that it fits within a regular workflow. As a practicing rheumatologist, I understand that time is a precious commodity.

The interventions are in partnership with frontline staff. We’ve received feedback that they feel pride participating in these initiatives. They can say, because of me, 30 patients followed up last month for high BP, or 10 patients took a referral to the Quitline last year. We celebrate these accomplishments with the staff.
 

What Are the Next Steps for These Programs?

Public-facing toolkits for both BP and Quit Connect programs are available online. We have implemented [these programs] in a rural setting, in an urban setting, in Milwaukee and in Atlanta, and we are looking in the future to do a larger, multistate implementation study. If folks are interested, we’d love to partner with them to look at disseminating this further.

A version of this article appeared on Medscape.com.

TOPLINE:

Patients with axial spondyloarthritis (axSpA) treated with bimekizumab had a lower incidence of uveitis than those receiving placebo in pooled clinical trial data.

METHODOLOGY:

• Researchers pooled data from two phase 3 trials, one phase 2b trial, and their open-label extensions to evaluate the incidence of uveitis in patients with radiographic and nonradiographic axSpA who were treated with bimekizumab.
• Patients received either bimekizumab 160 mg (n = 349) or placebo (n = 237) every 4 weeks in the pooled phase 3 data during a 16-week, double-blind treatment period, while 848 patients (mean age, 40.3 years; 71.5% men) received at least one dose of 160 mg bimekizumab in the overall phase 2b/3 pool.
• Outcomes included the incidence of uveitis events reported as exposure-adjusted incidence rates (EAIRs) and exposure-adjusted event rates reported per 100 patient-years.

TAKEAWAY:

• The proportion of patients experiencing uveitis was lower in those treated with bimekizumab than in those receiving placebo over 16 weeks (0.6% vs 4.6%; nominal P = .001).
• In patients with a history of uveitis, incidence was lower with bimekizumab than with placebo (6.2 vs 70.4 per 100 patient-years).
• Among patients receiving bimekizumab, the EAIR of uveitis was lower among those without a history of uveitis than in those with a history of the condition (0.6 vs 4.6 per 100 patient-years).
• A higher proportion of patients who experienced uveitis had a history of uveitis, compared with those who did not (56.0% vs 14.1%).

IN PRACTICE:

“These data suggest that [bimekizumab], a dual IL [interleukin]-17A/F inhibitor, may confer protective effects for uveitis in patients with axSpA,” the authors wrote.

SOURCE:

The study, led by Matthew A. Brown, Genomics England, London, England, and Martin Rudwaleit, Klinikum Bielefeld, University of Bielefeld, Germany, was published online in Annals of the Rheumatic Diseases.

LIMITATIONS:

The reporting of uveitis in the trials relied on the spontaneous reporting of adverse events, and not all events were evaluated by an ophthalmologist. The duration of the double-blind treatment period was relatively short, and the total number of patients with acute anterior uveitis was limited. Moreover, long-term placebo comparisons extending beyond 16 weeks were lacking.

DISCLOSURES:

The studies included in the pooled data were supported by UCB Pharma. Some authors reported financial ties with UCB and other pharmaceutical companies. Some authors reported being employees and shareholders of UCB Pharma.

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 axial spondyloarthritis (axSpA) treated with bimekizumab had a lower incidence of uveitis than those receiving placebo in pooled clinical trial data.

METHODOLOGY:

• Researchers pooled data from two phase 3 trials, one phase 2b trial, and their open-label extensions to evaluate the incidence of uveitis in patients with radiographic and nonradiographic axSpA who were treated with bimekizumab.
• Patients received either bimekizumab 160 mg (n = 349) or placebo (n = 237) every 4 weeks in the pooled phase 3 data during a 16-week, double-blind treatment period, while 848 patients (mean age, 40.3 years; 71.5% men) received at least one dose of 160 mg bimekizumab in the overall phase 2b/3 pool.
• Outcomes included the incidence of uveitis events reported as exposure-adjusted incidence rates (EAIRs) and exposure-adjusted event rates reported per 100 patient-years.

TAKEAWAY:

• The proportion of patients experiencing uveitis was lower in those treated with bimekizumab than in those receiving placebo over 16 weeks (0.6% vs 4.6%; nominal P = .001).
• In patients with a history of uveitis, incidence was lower with bimekizumab than with placebo (6.2 vs 70.4 per 100 patient-years).
• Among patients receiving bimekizumab, the EAIR of uveitis was lower among those without a history of uveitis than in those with a history of the condition (0.6 vs 4.6 per 100 patient-years).
• A higher proportion of patients who experienced uveitis had a history of uveitis, compared with those who did not (56.0% vs 14.1%).

IN PRACTICE:

“These data suggest that [bimekizumab], a dual IL [interleukin]-17A/F inhibitor, may confer protective effects for uveitis in patients with axSpA,” the authors wrote.

SOURCE:

The study, led by Matthew A. Brown, Genomics England, London, England, and Martin Rudwaleit, Klinikum Bielefeld, University of Bielefeld, Germany, was published online in Annals of the Rheumatic Diseases.

LIMITATIONS:

The reporting of uveitis in the trials relied on the spontaneous reporting of adverse events, and not all events were evaluated by an ophthalmologist. The duration of the double-blind treatment period was relatively short, and the total number of patients with acute anterior uveitis was limited. Moreover, long-term placebo comparisons extending beyond 16 weeks were lacking.

DISCLOSURES:

The studies included in the pooled data were supported by UCB Pharma. Some authors reported financial ties with UCB and other pharmaceutical companies. Some authors reported being employees and shareholders of UCB Pharma.

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 axial spondyloarthritis (axSpA) treated with bimekizumab had a lower incidence of uveitis than those receiving placebo in pooled clinical trial data.

METHODOLOGY:

• Researchers pooled data from two phase 3 trials, one phase 2b trial, and their open-label extensions to evaluate the incidence of uveitis in patients with radiographic and nonradiographic axSpA who were treated with bimekizumab.
• Patients received either bimekizumab 160 mg (n = 349) or placebo (n = 237) every 4 weeks in the pooled phase 3 data during a 16-week, double-blind treatment period, while 848 patients (mean age, 40.3 years; 71.5% men) received at least one dose of 160 mg bimekizumab in the overall phase 2b/3 pool.
• Outcomes included the incidence of uveitis events reported as exposure-adjusted incidence rates (EAIRs) and exposure-adjusted event rates reported per 100 patient-years.

TAKEAWAY:

• The proportion of patients experiencing uveitis was lower in those treated with bimekizumab than in those receiving placebo over 16 weeks (0.6% vs 4.6%; nominal P = .001).
• In patients with a history of uveitis, incidence was lower with bimekizumab than with placebo (6.2 vs 70.4 per 100 patient-years).
• Among patients receiving bimekizumab, the EAIR of uveitis was lower among those without a history of uveitis than in those with a history of the condition (0.6 vs 4.6 per 100 patient-years).
• A higher proportion of patients who experienced uveitis had a history of uveitis, compared with those who did not (56.0% vs 14.1%).

IN PRACTICE:

“These data suggest that [bimekizumab], a dual IL [interleukin]-17A/F inhibitor, may confer protective effects for uveitis in patients with axSpA,” the authors wrote.

SOURCE:

The study, led by Matthew A. Brown, Genomics England, London, England, and Martin Rudwaleit, Klinikum Bielefeld, University of Bielefeld, Germany, was published online in Annals of the Rheumatic Diseases.

LIMITATIONS:

The reporting of uveitis in the trials relied on the spontaneous reporting of adverse events, and not all events were evaluated by an ophthalmologist. The duration of the double-blind treatment period was relatively short, and the total number of patients with acute anterior uveitis was limited. Moreover, long-term placebo comparisons extending beyond 16 weeks were lacking.

DISCLOSURES:

The studies included in the pooled data were supported by UCB Pharma. Some authors reported financial ties with UCB and other pharmaceutical companies. Some authors reported being employees and shareholders of UCB Pharma.

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.

Certain extraintestinal manifestations (EIMs) in inflammatory bowel disease (IBD) have distinct clinical, serologic, and genetic associations that reveal underlying mechanisms and indicate targets for new or existing drugs, according to a recent study.

For instance, antinuclear cytoplastic antibody is associated with primary sclerosing cholangitis (PSC) in Crohn’s disease, and CPEB4 genetic variation is associated with skin manifestations.

“Up to 40% of people with IBD suffer with symptoms from inflammation that occurs outside the gut, particularly affecting the liver, skin, and joints. These symptoms can often have a bigger impact on quality of life than the gut inflammation itself and can actually be life-threatening,” said senior author Dermot McGovern, MD, PhD, AGAF, director of translational medicine at the F. Widjaja Foundation Inflammatory Bowel Disease and Immunobiology Research Institute at Cedars-Sinai Medical Center, Los Angeles.

Cedars-Sinai Medical Center

“With the advances in therapies for IBD, including availability of gut-selective agents, treatment choices often incorporate whether a patient has one of these manifestations or not,” he said. “We need to understand who is at increased risk of these and why.”

The study was published in Gastroenterology .
 

Analyzing Associations

Dr. McGovern and colleagues analyzed data for 12,083 unrelated European ancestry IBD cases with presence or absence of EIMs across four cohorts in the Cedars-Sinai Medical Center IBD Research Repository, National Institute for Diabetes and Digestive and Kidney Diseases IBD Genetics Consortium, Sinai Helmsley Alliance for Research Excellence Consortium, and Risk Stratification and Identification of Immunogenetic and Microbial Markers of Rapid Disease Progression in Children with Crohn’s Disease.

In particular, the researchers looked at EIM phenotypes such as ankylosing spondylitis and sacroiliitis, PSC, peripheral arthritis, and skin and ocular manifestations. They analyzed clinical and serologic parameters through regression analyses using a mixed-effects model, as well as within-case logistic regression for genetic associations.

Overall, 14% of patients had at least one EIM. Contrary to previous reports, only 2% had multiple EIMs, and most co-occurrences were negatively correlated. Nearly all EIMs were more common in Crohn’s disease, except for PSC, which was more common in ulcerative colitis.

In general, EIMs occurred more often in women, particularly with Crohn’s disease and colonic disease location, and in patients who required surgery. Jewish ancestry was associated with psoriasis and overall skin manifestations.

Smoking increased the risk for multiple EIMs, except for PSC, where there appeared to be a “protective” effect. Older age at diagnosis and a family history of IBD were associated with increased risk for certain EIMs as well.

In addition, the research team noted multiple serologic associations, such as immunoglobulin (Ig) G and IgA, perinuclear antinuclear cytoplastic antibodies, and anti–Pseudomonas fluorescens–associated sequences with any EIM, as well as particular associations with PSC, such as anti-Saccharomyces cerevisiae antibodies and anti-flagellin.

There were also genome-wide significant associations within the major histocompatibility complex and CPEB4. Genetic associations implicated tumor necrosis factor, Janus kinase-signal transducer and activator of transcription, and interleukin 6 as potential targets for EIMs.

“We are working with colleagues across the world to increase the sample size, as we believe there is more to find,” Dr. McGovern said. “Importantly, this includes non-European ancestry subjects, as there is an urgent need to increase the diversity of populations we study so advances in clinical care are available to all communities.”
 

Considering Target Therapies

As medicine becomes more specialized, physicians should remember to consider the whole patient while choosing treatment strategies.

“Sometimes doctors wear blinders to the whole person, and it’s important to be aware of a holistic approach, where a gastroenterologist also asks about potential joint inflammation or a rheumatologist asks about bowel inflammation,” said David Rubin, MD, AGAF, chief of the Section of Gastroenterology, Hepatology and Nutrition at the University of Chicago Medicine, Chicago.

Dr. Rubin, who wasn’t involved with this study, has researched and published on EIMs in IBD. He and colleagues analyzed the prevalence, pathophysiology, and clinical presentation of EIMs to better understand possibilities for disease management.

A version of this article appeared on Medscape.com.

Certain extraintestinal manifestations (EIMs) in inflammatory bowel disease (IBD) have distinct clinical, serologic, and genetic associations that reveal underlying mechanisms and indicate targets for new or existing drugs, according to a recent study.

For instance, antinuclear cytoplastic antibody is associated with primary sclerosing cholangitis (PSC) in Crohn’s disease, and CPEB4 genetic variation is associated with skin manifestations.

“Up to 40% of people with IBD suffer with symptoms from inflammation that occurs outside the gut, particularly affecting the liver, skin, and joints. These symptoms can often have a bigger impact on quality of life than the gut inflammation itself and can actually be life-threatening,” said senior author Dermot McGovern, MD, PhD, AGAF, director of translational medicine at the F. Widjaja Foundation Inflammatory Bowel Disease and Immunobiology Research Institute at Cedars-Sinai Medical Center, Los Angeles.

Cedars-Sinai Medical Center

“With the advances in therapies for IBD, including availability of gut-selective agents, treatment choices often incorporate whether a patient has one of these manifestations or not,” he said. “We need to understand who is at increased risk of these and why.”

The study was published in Gastroenterology .
 

Analyzing Associations

Dr. McGovern and colleagues analyzed data for 12,083 unrelated European ancestry IBD cases with presence or absence of EIMs across four cohorts in the Cedars-Sinai Medical Center IBD Research Repository, National Institute for Diabetes and Digestive and Kidney Diseases IBD Genetics Consortium, Sinai Helmsley Alliance for Research Excellence Consortium, and Risk Stratification and Identification of Immunogenetic and Microbial Markers of Rapid Disease Progression in Children with Crohn’s Disease.

In particular, the researchers looked at EIM phenotypes such as ankylosing spondylitis and sacroiliitis, PSC, peripheral arthritis, and skin and ocular manifestations. They analyzed clinical and serologic parameters through regression analyses using a mixed-effects model, as well as within-case logistic regression for genetic associations.

Overall, 14% of patients had at least one EIM. Contrary to previous reports, only 2% had multiple EIMs, and most co-occurrences were negatively correlated. Nearly all EIMs were more common in Crohn’s disease, except for PSC, which was more common in ulcerative colitis.

In general, EIMs occurred more often in women, particularly with Crohn’s disease and colonic disease location, and in patients who required surgery. Jewish ancestry was associated with psoriasis and overall skin manifestations.

Smoking increased the risk for multiple EIMs, except for PSC, where there appeared to be a “protective” effect. Older age at diagnosis and a family history of IBD were associated with increased risk for certain EIMs as well.

In addition, the research team noted multiple serologic associations, such as immunoglobulin (Ig) G and IgA, perinuclear antinuclear cytoplastic antibodies, and anti–Pseudomonas fluorescens–associated sequences with any EIM, as well as particular associations with PSC, such as anti-Saccharomyces cerevisiae antibodies and anti-flagellin.

There were also genome-wide significant associations within the major histocompatibility complex and CPEB4. Genetic associations implicated tumor necrosis factor, Janus kinase-signal transducer and activator of transcription, and interleukin 6 as potential targets for EIMs.

“We are working with colleagues across the world to increase the sample size, as we believe there is more to find,” Dr. McGovern said. “Importantly, this includes non-European ancestry subjects, as there is an urgent need to increase the diversity of populations we study so advances in clinical care are available to all communities.”
 

Considering Target Therapies

As medicine becomes more specialized, physicians should remember to consider the whole patient while choosing treatment strategies.

“Sometimes doctors wear blinders to the whole person, and it’s important to be aware of a holistic approach, where a gastroenterologist also asks about potential joint inflammation or a rheumatologist asks about bowel inflammation,” said David Rubin, MD, AGAF, chief of the Section of Gastroenterology, Hepatology and Nutrition at the University of Chicago Medicine, Chicago.

Dr. Rubin, who wasn’t involved with this study, has researched and published on EIMs in IBD. He and colleagues analyzed the prevalence, pathophysiology, and clinical presentation of EIMs to better understand possibilities for disease management.

A version of this article appeared on Medscape.com.

Certain extraintestinal manifestations (EIMs) in inflammatory bowel disease (IBD) have distinct clinical, serologic, and genetic associations that reveal underlying mechanisms and indicate targets for new or existing drugs, according to a recent study.

For instance, antinuclear cytoplastic antibody is associated with primary sclerosing cholangitis (PSC) in Crohn’s disease, and CPEB4 genetic variation is associated with skin manifestations.

“Up to 40% of people with IBD suffer with symptoms from inflammation that occurs outside the gut, particularly affecting the liver, skin, and joints. These symptoms can often have a bigger impact on quality of life than the gut inflammation itself and can actually be life-threatening,” said senior author Dermot McGovern, MD, PhD, AGAF, director of translational medicine at the F. Widjaja Foundation Inflammatory Bowel Disease and Immunobiology Research Institute at Cedars-Sinai Medical Center, Los Angeles.

Cedars-Sinai Medical Center

“With the advances in therapies for IBD, including availability of gut-selective agents, treatment choices often incorporate whether a patient has one of these manifestations or not,” he said. “We need to understand who is at increased risk of these and why.”

The study was published in Gastroenterology .
 

Analyzing Associations

Dr. McGovern and colleagues analyzed data for 12,083 unrelated European ancestry IBD cases with presence or absence of EIMs across four cohorts in the Cedars-Sinai Medical Center IBD Research Repository, National Institute for Diabetes and Digestive and Kidney Diseases IBD Genetics Consortium, Sinai Helmsley Alliance for Research Excellence Consortium, and Risk Stratification and Identification of Immunogenetic and Microbial Markers of Rapid Disease Progression in Children with Crohn’s Disease.

In particular, the researchers looked at EIM phenotypes such as ankylosing spondylitis and sacroiliitis, PSC, peripheral arthritis, and skin and ocular manifestations. They analyzed clinical and serologic parameters through regression analyses using a mixed-effects model, as well as within-case logistic regression for genetic associations.

Overall, 14% of patients had at least one EIM. Contrary to previous reports, only 2% had multiple EIMs, and most co-occurrences were negatively correlated. Nearly all EIMs were more common in Crohn’s disease, except for PSC, which was more common in ulcerative colitis.

In general, EIMs occurred more often in women, particularly with Crohn’s disease and colonic disease location, and in patients who required surgery. Jewish ancestry was associated with psoriasis and overall skin manifestations.

Smoking increased the risk for multiple EIMs, except for PSC, where there appeared to be a “protective” effect. Older age at diagnosis and a family history of IBD were associated with increased risk for certain EIMs as well.

In addition, the research team noted multiple serologic associations, such as immunoglobulin (Ig) G and IgA, perinuclear antinuclear cytoplastic antibodies, and anti–Pseudomonas fluorescens–associated sequences with any EIM, as well as particular associations with PSC, such as anti-Saccharomyces cerevisiae antibodies and anti-flagellin.

There were also genome-wide significant associations within the major histocompatibility complex and CPEB4. Genetic associations implicated tumor necrosis factor, Janus kinase-signal transducer and activator of transcription, and interleukin 6 as potential targets for EIMs.

“We are working with colleagues across the world to increase the sample size, as we believe there is more to find,” Dr. McGovern said. “Importantly, this includes non-European ancestry subjects, as there is an urgent need to increase the diversity of populations we study so advances in clinical care are available to all communities.”
 

Considering Target Therapies

As medicine becomes more specialized, physicians should remember to consider the whole patient while choosing treatment strategies.

“Sometimes doctors wear blinders to the whole person, and it’s important to be aware of a holistic approach, where a gastroenterologist also asks about potential joint inflammation or a rheumatologist asks about bowel inflammation,” said David Rubin, MD, AGAF, chief of the Section of Gastroenterology, Hepatology and Nutrition at the University of Chicago Medicine, Chicago.

Dr. Rubin, who wasn’t involved with this study, has researched and published on EIMs in IBD. He and colleagues analyzed the prevalence, pathophysiology, and clinical presentation of EIMs to better understand possibilities for disease management.

A version of this article appeared on Medscape.com.

TOPLINE:

Compared with dipeptidyl peptidase 4 (DPP-4) inhibitors, glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are associated with a lower risk for all-cause mortality and major adverse cardiovascular events (MACE) in patients with immune-mediated inflammatory diseases (IMIDs) and type 2 diabetes (T2D).

METHODOLOGY:

• GLP-1 RAs reduce the risk for all-cause mortality, cardiovascular mortality, and stroke in patients with diabetes. However, previous trials have excluded those with IMIDs, leaving a gap in understanding the cardioprotective effects of GLP-1 RAs in this population.
• Researchers conducted a population-based cohort study to assess if patients with an IMID derive greater benefits from GLP-1 RAs than DPP-4 inhibitors.
• They used administrative health data from British Columbia, Canada, to include 10,855 patients with IMIDs (rheumatoid arthritis, psoriatic disease, ankylosing spondylitis, inflammatory bowel disease, or systemic autoimmune rheumatic disease) and T2D who initiated either GLP-1 RA (n = 3570) or DPP-4 inhibitor (n = 7285).
• The mean follow-up was 1.46 and 1.88 years in the GLP-1 RA and DPP-4 inhibitor cohorts, respectively.
• The primary outcome was all-cause mortality, and the secondary outcome was MACE, including cardiovascular death, myocardial infarction, and ischemic stroke.

TAKEAWAY:

• The risk for all-cause mortality was 52% lower in patients who initiated GLP-1 RAs than in those who initiated DPP-4 inhibitors (weighted hazard ratio [HR], 0.48; 95% CI, 0.31-0.75).
• Additionally, patients initiating DPP-4 inhibitors.
• In the subgroup of patients with GLP-1 RAs had a significantly lower risk for MACE (weighted HR, 0.66; 95% CI, 0.50-0.88), particularly myocardial infarction (weighted HR, 0.62; 95% CI, 0.40-0.96), than those initiating rheumatoid arthritis and T2D, those who initiated GLP-1 RAs had a 55% lower risk for all-cause mortality and 61% lower risk for MACE than those who initiated DPP-4 inhibitors.

IN PRACTICE:

“This corresponds to nine fewer deaths and 11 fewer MACE per 1000 person-years, respectively, supporting the hypothesis that these agents have a cardioprotective effect in this high-risk population,” the authors wrote.

SOURCE:

This study was led by Derin Karacabeyli, MD, Division of Rheumatology, Department of Medicine, University of British Columbia, Vancouver, Canada, and was published online on August 8, 2024, in PLOS ONE.

LIMITATIONS:

The study’s dependence on administrative health data might have resulted in incomplete capture of comorbidities, particularly obesity. The mean follow-up period was relatively short, which might have limited the long-term applicability of these findings. The accuracy of the case definitions for IMIDs and T2D, according to International Classification of Diseases codes, could not be fully ascertained.

DISCLOSURES:

The study was supported by grants from the Canadian Institutes of Health Research. Two authors declared receiving research support, consulting fees, or participating in advisory boards outside 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:

Compared with dipeptidyl peptidase 4 (DPP-4) inhibitors, glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are associated with a lower risk for all-cause mortality and major adverse cardiovascular events (MACE) in patients with immune-mediated inflammatory diseases (IMIDs) and type 2 diabetes (T2D).

METHODOLOGY:

• GLP-1 RAs reduce the risk for all-cause mortality, cardiovascular mortality, and stroke in patients with diabetes. However, previous trials have excluded those with IMIDs, leaving a gap in understanding the cardioprotective effects of GLP-1 RAs in this population.
• Researchers conducted a population-based cohort study to assess if patients with an IMID derive greater benefits from GLP-1 RAs than DPP-4 inhibitors.
• They used administrative health data from British Columbia, Canada, to include 10,855 patients with IMIDs (rheumatoid arthritis, psoriatic disease, ankylosing spondylitis, inflammatory bowel disease, or systemic autoimmune rheumatic disease) and T2D who initiated either GLP-1 RA (n = 3570) or DPP-4 inhibitor (n = 7285).
• The mean follow-up was 1.46 and 1.88 years in the GLP-1 RA and DPP-4 inhibitor cohorts, respectively.
• The primary outcome was all-cause mortality, and the secondary outcome was MACE, including cardiovascular death, myocardial infarction, and ischemic stroke.

TAKEAWAY:

• The risk for all-cause mortality was 52% lower in patients who initiated GLP-1 RAs than in those who initiated DPP-4 inhibitors (weighted hazard ratio [HR], 0.48; 95% CI, 0.31-0.75).
• Additionally, patients initiating DPP-4 inhibitors.
• In the subgroup of patients with GLP-1 RAs had a significantly lower risk for MACE (weighted HR, 0.66; 95% CI, 0.50-0.88), particularly myocardial infarction (weighted HR, 0.62; 95% CI, 0.40-0.96), than those initiating rheumatoid arthritis and T2D, those who initiated GLP-1 RAs had a 55% lower risk for all-cause mortality and 61% lower risk for MACE than those who initiated DPP-4 inhibitors.

IN PRACTICE:

“This corresponds to nine fewer deaths and 11 fewer MACE per 1000 person-years, respectively, supporting the hypothesis that these agents have a cardioprotective effect in this high-risk population,” the authors wrote.

SOURCE:

This study was led by Derin Karacabeyli, MD, Division of Rheumatology, Department of Medicine, University of British Columbia, Vancouver, Canada, and was published online on August 8, 2024, in PLOS ONE.

LIMITATIONS:

The study’s dependence on administrative health data might have resulted in incomplete capture of comorbidities, particularly obesity. The mean follow-up period was relatively short, which might have limited the long-term applicability of these findings. The accuracy of the case definitions for IMIDs and T2D, according to International Classification of Diseases codes, could not be fully ascertained.

DISCLOSURES:

The study was supported by grants from the Canadian Institutes of Health Research. Two authors declared receiving research support, consulting fees, or participating in advisory boards outside 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:

Compared with dipeptidyl peptidase 4 (DPP-4) inhibitors, glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are associated with a lower risk for all-cause mortality and major adverse cardiovascular events (MACE) in patients with immune-mediated inflammatory diseases (IMIDs) and type 2 diabetes (T2D).

METHODOLOGY:

• GLP-1 RAs reduce the risk for all-cause mortality, cardiovascular mortality, and stroke in patients with diabetes. However, previous trials have excluded those with IMIDs, leaving a gap in understanding the cardioprotective effects of GLP-1 RAs in this population.
• Researchers conducted a population-based cohort study to assess if patients with an IMID derive greater benefits from GLP-1 RAs than DPP-4 inhibitors.
• They used administrative health data from British Columbia, Canada, to include 10,855 patients with IMIDs (rheumatoid arthritis, psoriatic disease, ankylosing spondylitis, inflammatory bowel disease, or systemic autoimmune rheumatic disease) and T2D who initiated either GLP-1 RA (n = 3570) or DPP-4 inhibitor (n = 7285).
• The mean follow-up was 1.46 and 1.88 years in the GLP-1 RA and DPP-4 inhibitor cohorts, respectively.
• The primary outcome was all-cause mortality, and the secondary outcome was MACE, including cardiovascular death, myocardial infarction, and ischemic stroke.

TAKEAWAY:

• The risk for all-cause mortality was 52% lower in patients who initiated GLP-1 RAs than in those who initiated DPP-4 inhibitors (weighted hazard ratio [HR], 0.48; 95% CI, 0.31-0.75).
• Additionally, patients initiating DPP-4 inhibitors.
• In the subgroup of patients with GLP-1 RAs had a significantly lower risk for MACE (weighted HR, 0.66; 95% CI, 0.50-0.88), particularly myocardial infarction (weighted HR, 0.62; 95% CI, 0.40-0.96), than those initiating rheumatoid arthritis and T2D, those who initiated GLP-1 RAs had a 55% lower risk for all-cause mortality and 61% lower risk for MACE than those who initiated DPP-4 inhibitors.

IN PRACTICE:

“This corresponds to nine fewer deaths and 11 fewer MACE per 1000 person-years, respectively, supporting the hypothesis that these agents have a cardioprotective effect in this high-risk population,” the authors wrote.

SOURCE:

This study was led by Derin Karacabeyli, MD, Division of Rheumatology, Department of Medicine, University of British Columbia, Vancouver, Canada, and was published online on August 8, 2024, in PLOS ONE.

LIMITATIONS:

The study’s dependence on administrative health data might have resulted in incomplete capture of comorbidities, particularly obesity. The mean follow-up period was relatively short, which might have limited the long-term applicability of these findings. The accuracy of the case definitions for IMIDs and T2D, according to International Classification of Diseases codes, could not be fully ascertained.

DISCLOSURES:

The study was supported by grants from the Canadian Institutes of Health Research. Two authors declared receiving research support, consulting fees, or participating in advisory boards outside 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.