TOPLINE:

A meta-analysis showed no significant differences between JAK inhibitor use and TNF antagonist use in terms of the risk for serious infections or malignant neoplasms in patients with immune-mediated inflammatory diseases (IMIDs). However, JAK inhibitor use was associated with a slightly higher risk for venous thromboembolism (VTE) than TNF antagonist use.

METHODOLOGY:

• Researchers conducted a systematic review and meta-analysis of 42 head-to-head comparative effectiveness studies (41 published and one unpublished) of JAK inhibitors and TNF antagonists in treating IMIDs, covering studies published up to June 25, 2025.
• They included studies of adults with IMIDs such as rheumatoid arthritis, inflammatory bowel disease, psoriasis, psoriatic arthritis, or spondyloarthropathy who were treated with JAK inhibitors or TNF antagonists.
• A total of 813,881 patients with IMIDs (76.5% women) were included, with 128,705 treated with JAK inhibitors (median age, 55.7 years) and 685,176 treated with TNF antagonists (median age, 51.5 years).
• The primary outcomes were risks for serious infections, malignant neoplasms, major adverse cardiovascular events (MACEs), and VTE.

TAKEAWAY:

• No significant difference was found in the risk for serious infections between patients treated with JAK inhibitors and those treated with TNF antagonists in a meta-analysis of 18 cohorts, with incidence rates of 3.79 and 3.03 per 100 person-years, respectively.
• The risks for malignant neoplasms and MACEs did not differ significantly between the two treatment groups (based on the analysis of 17 and 29 cohorts, respectively).
• JAK inhibitor use was associated with a slightly higher risk for VTE than TNF antagonist use in a meta-analysis of 16 cohorts (pooled hazard ratio, 1.26; 95% CI, 1.03-1.54; moderate heterogeneity).
• In patients with rheumatoid arthritis, JAK inhibitor use was linked to a 31% higher risk for VTE than TNF antagonist use (hazard ratio, 1.31; 95% CI, 1.07-1.60), whereas in patients with inflammatory bowel disease, no significant difference in the risk for VTE was found between the two treatment groups.

IN PRACTICE:

“[The study] findings support JAK inhibitor use with appropriate patient selection, monitoring, and strategies to optimize disease control,” the authors of the study wrote.

SOURCE:

The study was led by Virginia Solitano, MD, IRCCS Ospedale San Raffaele, Università Vita-Salute San Raffaele in Milan, Italy. It was published online on September 10, 2025, in JAMA Network Open.

LIMITATIONS:

The absence of randomization and limited patient data may affect causal inference. Despite subgroup analyses and meta-regression, heterogeneity was not fully accounted for. The median follow-up duration of less than 2 years limited the ability to assess long-term safety, particularly for malignant neoplasms.

DISCLOSURES:

The study was supported by the Crohn’s and Colitis Foundation. One author was supported by awards from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the National Institute on Aging. Another author was supported by the National Institute of Diabetes and Digestive and Kidney Diseases. Some authors disclosed receiving personal fees, consulting fees, speaker fees, royalties, advisory board fees, and/or research support/grants from various sources, including AbbVie, Janssen, and Pfizer.

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