Ann Rheum Dis

Slightly elevated cancer risk seen with JAK inhibitors in RA patients

July 2, 2025

Study details: This observational cohort study analyzed 6,544 treatment episodes from the German RABBIT register between 2017 and 2024, comparing incident malignancy risk (excluding nonmelanoma skin cancer) in rheumatoid arthritis patients initiating Janus kinase inhibitors (JAKis, mainly baricitinib and tofacitinib) vs. biologic DMARDs (bDMARDs, predominantly tumor necrosis factor inhibitors). Incidence rates (IRs) per 1,000 patient-years and hazard ratios (HRs) were estimated using inverse probability weighted Cox models adjusted for confounders.

Findings:

• Among 2,285 JAKi and 4,259 bDMARD episodes, 88 and 135 malignancies occurred, respectively.
• IR was 11.6 (95% CI, 9.3–14.3) for JAKis vs. 8.9 (95% CI, 7.4–10.5) for bDMARDs.
• The adjusted HR for malignancy with JAKis vs. bDMARDs was 1.40 (95% CI, 1.09–1.80), indicating a modestly increased risk. Risk elevation was observed only after treatment duration exceeded 16 months and was more pronounced in patients aged ≥60 years, those with ≥3 prior conventional synthetic DMARDs, and those with high disease activity.

Clinical impact: A small but statistically significant increase in malignancy risk was observed with JAK inhibitors compared with bDMARDs in rheumatoid arthritis, particularly with longer treatment duration and in higher-risk subgroups. Clinicians should weigh this risk against the benefits of disease control, as inadequate control itself is associated with malignancy risk. Careful patient selection and monitoring for malignancy are warranted when prescribing JAKis.

Source:

Schaefer M, et al. (2025, June 25). Ann Rheum Dis. Comparative risk of incident malignancies in rheumatoid arthritis patients treated with Janus kinase inhibitors or bDMARDs: observational data from the German RABBIT register. https://pubmed.ncbi.nlm.nih.gov/40571478/