Home›Allergy & Immunology› Interleukin inhibitors in rheumatoid arthritis are associated with increased risk of serious infections and discontinuations
Interleukin inhibitors in rheumatoid arthritis are associated with increased risk of serious infections and discontinuationsAnalysis shows safety risks for rheumatoid arthritis interleukin inhibitors
Frontiers in MedicinePublished September 23, 2026DOI ↗Editorial oversight: Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease
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Key Takeaway
Note that interleukin inhibitors are associated with increased risks of serious infections and treatment discontinuation.
This systematic review and network meta-analysis evaluated the safety profile of interleukin inhibitors in patients with rheumatoid arthritis, incorporating data from 12,915 patients. The analysis identified several significant associations regarding safety outcomes. Specifically, patients receiving interleukin inhibitors showed increased odds of adverse events (OR 1.15), serious adverse events (OR 1.22), and infections (OR 1.10). Notably, serious infections were associated with an OR of 1.35, and adverse events leading to treatment discontinuation were associated with an OR of 1.65.
Additional findings included increased odds for gastrointestinal adverse events (OR 1.38), neurological adverse events (OR 1.32), skin and subcutaneous tissue adverse events (OR 1.86), and abnormal laboratory investigations (OR 1.99). Conversely, musculoskeletal and connective tissue adverse events were associated with a decrease (OR 0.77).
The authors note several limitations, including sparse networks, short trial durations, and uncertainty regarding rare events. There was also significant heterogeneity in background methotrexate and DMARD use, along with a lack of long-term safety data. Clinical application of these findings should be tempered by these limitations and tailored to individual patient circumstances.
How this fits prior evidence
This network meta-analysis addresses the safety profile of interleukin inhibitors in rheumatoid arthritis. While previous evidence has explored the cardiovascular risk of Janus kinase inhibitors and the potential of mesenchymal stromal cells for immune homeostasis, this study specifically quantifies the risks of infections (OR 1.35) and treatment discontinuations (OR 1.65) associated with interleukin inhibitors. It provides a broader safety overview of the interleukin inhibitor class despite noted limitations in trial duration and network density.
Living with rheumatoid arthritis means balancing the need for effective treatment against the risk of side effects. A large analysis of 12,915 patients looked closely at the safety of interleukin inhibitors, a type of medication used to manage this condition. The researchers found that while these drugs are used to treat the disease, they are associated with an increased risk of several types of complications.
The data showed higher rates of general adverse events, serious adverse events, and infections. Specifically, patients taking these medications saw more gastrointestinal issues, skin problems, and abnormal lab results. There was also a notable increase in cases where patients had to stop their treatment due to these side effects. Interestingly, the study did find a decrease in musculoskeletal and connective tissue issues.
It is important to keep these findings in perspective. The study notes that the data comes from relatively short trials and may not show the full picture of long-term safety. Because of factors like the variety of other medications patients were taking and the rarity of some events, these results should be discussed with a doctor. Every patient's situation is unique, and your medical team can help weigh these risks against the benefits for your specific case.
What this means for you:
Interleukin inhibitors for rheumatoid arthritis are linked to higher rates of infection and various side effects.
Common questions
Are there risks to taking interleukin inhibitors for rheumatoid arthritis?
Yes, the study of 12,915 patients found that these medications are associated with increased adverse events and serious adverse events. Specifically, there were higher rates of infections, gastrointestinal issues, and skin or subcutaneous tissue problems. Because of these risks, your doctor should help you weigh the benefits against the potential side effects.
What specific side effects were linked to these medications?
The analysis showed increased rates of several issues, including gastrointestinal problems, skin issues, and abnormal laboratory investigations. There was also a significant increase in cases where patients had to stop their treatment due to these side effects. However, the study did find a decrease in musculoskeletal and connective tissue issues.
How certain are these safety findings?
The results should be interpreted with caution. The study notes several limitations, including short trial durations, a lack of long-term safety data, and the fact that many patients were taking other medications at the same time. You should discuss these specific findings with your healthcare provider to understand how they apply to your treatment.
BackgroundThe safety of biological agents in the treatment of rheumatoid arthritis (RA) is an important factor affecting patient prognosis and treatment adherence. Among them, interleukin inhibitors are an important category. However, the safety of different types of interleukin inhibitors used to treat RA has not been adequately evaluated. The purpose of this study is to evaluate the safety of interleukin inhibitors for the treatment of RA.MethodsComputer-based searches were conducted in PubMed, the Cochrane Library, Embase, and CNKI to retrieve randomized controlled trials of interleukin inhibitors for the treatment of RA up to March 2026. Literature screening, data extraction, and risk of bias assessment were independently performed by two researchers, and the data were analyzed using Stata 13.1 and the R 4.5.3’s gemtc package. The network meta-analysis was performed using a Markov Chain Monte Carlo (MCMC) consistent model. Odds ratios (OR) were used as the measure of effect size.ResultsA total of 24 RCTs involving 12,915 patients with RA were included. The use of interleukin inhibitors was associated with the occurrence of adverse events (AE) (OR = 1.15, 95% CI [1.09, 1.21], p < 0.0001), serious adverse events (SAEs) (OR = 1.22, 95% CI [1.08, 1.38], p = 0.001), infections (OR = 1.10, 95% CI [1.02, 1.18], p = 0.007), serious infections (OR = 1.35, 95% CI [1.00, 1.83], p = 0.046), AEs leading to discontinuation (OR = 1.65, 95% CI [1.32, 2.06], p < 0.0001), general disorders and administration site conditions (OR = 1.85, 95% CI [1.49, 2.29], p < 0.0001), gastrointestinal AEs (OR = 1.38, 95% CI [1.04, 1.83], p = 0.002), neurological AEs (OR = 1.32, 95% CI [1.03, 1.68], p = 0.024), skin and subcutaneous tissues AEs (OR = 1.86, 95% CI [1.52, 2.28], p < 0.0001), abnormal laboratory investigations (OR = 1.99, 95% CI [1.59, 2.48], p < 0.0001), and increased ALT in laboratory investigations (OR = 1.88, 95% CI [1.36, 2.60], p < 0.0001). However, interleukin inhibitor use was associated with a decrease in musculoskeletal and connective tissue AEs (OR = 0.77, 95% CI [0.62, 0.95], p = 0.014). It is worth noting that characteristics of the included studies may have affected the results, such as sparse networks, short trial durations, rare-event uncertainty, heterogeneity in background MTX/DMARD use, and lack of long-term safety data.ConclusionsOverall, the AEs caused by different interleukin inhibitors vary. However, in clinical practice, our conclusion should be interpreted cautiously according to individual patient circumstances.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier 420261338669.
