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Nonmelanoma Skin Cancer Risk With JAK Inhibitors Compared to Interleukin-6 Receptor Inhibitors in Rheumatoid

Zixing Tian1,2, Lianne Kearsley-Fleet1,2, Sizheng Steven Zhao1,2

  • 1Centre for Musculoskeletal Research, Division of Musculoskeletal and Dermatological Sciences, School of Biological Sciences, Faculty of Biology Medicine and Health, University of Manchester, Manchester, United Kingdom.

Arthritis & Rheumatology (Hoboken, N.J.)
|July 9, 2026
PubMed
Abstract

Insights

Janus kinase inhibitors (JAKi) may slightly increase non-melanoma skin cancer (NMSC) risk compared to interleukin-6 receptor inhibitors (IL-6Ri) in rheumatoid arthritis (RA) patients. This risk, though not statistically significant, warrants consideration alongside treatment benefits.

Area of Science:

  • Rheumatology
  • Oncology
  • Pharmacology

Background:

  • Non-melanoma skin cancer (NMSC) is a significant concern for rheumatoid arthritis (RA) patients.
  • Assessing the comparative risk of NMSC between Janus kinase inhibitors (JAKi) and interleukin-6 receptor inhibitors (IL-6Ri) is crucial for patient safety.

Purpose of the Study:

  • To compare the risk of developing NMSC in RA patients treated with JAK inhibitors versus IL-6 receptor inhibitors.
  • To inform clinical decision-making regarding the selection of biologic therapies in RA management.

Main Methods:

  • Utilized data from the British Society for Rheumatology Rheumatoid Arthritis Register (BSRBR-RA) linked to cancer registries.
  • Employed Cox proportional hazards models with inverse probability of treatment weighting (IPTW) for primary and secondary on-treatment analyses.
  • Included RA patients initiating their first JAKi or IL-6Ri, excluding the initial 90 days of treatment.

Main Results:

  • The primary analysis included 3,985 RA patients, with 116 NMSC events.
  • The IPTW hazard ratio for JAKi versus IL-6Ri was 1.64 (95% CI: 0.85, 3.17), indicating a potentially higher risk.
  • An absolute rate difference suggested approximately one additional NMSC event per 307 patients treated with JAKi versus IL-6Ri over one year.

Conclusions:

  • Initiation of JAKi was associated with a clinically small, possibly higher NMSC risk compared to IL-6Ri, though not statistically significant.
  • Rheumatologists and patients should balance the potential NMSC risk against the therapeutic benefits of JAKi and IL-6Ri.
  • Further long-term studies may be needed to definitively establish the comparative NMSC risk between these drug classes.

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