A new study published in Annals of the Rheumatic Diseases reports that patients with rheumatoid arthritis (RA) who receive Janus kinase inhibitors show a small but statistically significant increase in malignancy risk compared with those treated with biologic disease modifying antirheumatic drugs. The increased risk appeared particularly notable in certain patient groups and during longer periods of treatment.
The research drew on data from RABBIT, the German registry that tracks long term outcomes of biologic and targeted therapies in adults with RA. The analysis included treatment episodes that began between January 2017 and December 2020, with follow up extending to June 2024. Among 2285 treatment episodes involving Janus kinase inhibitors, mainly baricitinib and tofacitinib, there were 88 recorded malignancies. Among 4259 biologic therapy episodes, primarily involving tumor necrosis factor inhibitors, 135 malignancies were documented. Nonmelanoma skin cancer was excluded from the analysis.
The incidence rate reached 11.6 cases per 1000 patient years in the Janus kinase inhibitor group, compared with 8.9 cases per 1000 patient years in the biologic therapy group. After statistical adjustment using an inverse probability weighted Cox model, the hazard ratio for malignancy was 1.40 when comparing Janus kinase inhibitors with biologic drugs. The increase in cancer risk appeared only in treatment courses that extended beyond sixteen months. Higher risk was also seen in certain patient subgroups, including individuals aged sixty years and older, those who had previously received three or more conventional synthetic therapies, and those who started treatment with high disease activity.
The findings support earlier evidence, including a meta-analysis by Russell and colleagues, which found that Janus kinase inhibitors had malignancy rates similar to placebo and methotrexate but showed higher incidence when compared with tumor necrosis factor inhibitors. That analysis, which included data from sixty-two randomized trials and sixteen long term extension studies covering more than eighty-two thousand person years of drug exposure, reported malignancy rates ranging from 1.15 to 1.26 cases per 100 patient years. Across multiple comparisons, no increased cancer risk was detected relative to placebo or methotrexate, while a higher risk consistently appeared when compared with tumor necrosis factor inhibitors. These trends remained stable even when nonmelanoma skin cancers were assessed separately and when long term extension data were incorporated.
Investigators concluded that clinicians must weigh the observed cancer risk against the known dangers of poorly controlled RA, which itself contributes to elevated malignancy rates. They noted that treatment decisions should consider patient age, prior therapy history, and disease activity at the time of treatment initiation. The authors also emphasized that understanding the profiles of patients who may face increased risk can support more personalized treatment strategies and guide decisions about the appropriate intensity of cancer screening for individuals currently receiving, or who have previously received, Janus kinase inhibitor therapy.
References
- Schaefer M, Purschke A, Zietemann V, Rudi T, Meissner Y, Richter A, Berger S, Rockwitz K, Krüger K, Schneider KM, Regierer AC, Strangfeld A. Comparative risk of incident malignancies in rheumatoid arthritis patients treated with Janus kinase inhibitors or bDMARDs: observational data from the German RABBIT register. Ann Rheum Dis. 2025 Nov;84(11):1779-1790.
- Russell MD, Stovin C, Alveyn E, Adeyemi O, Chan CKD, Patel V, Adas MA, Atzeni F, Ng KKH, Rutherford AI, Norton S, Cope AP, Galloway JB. JAK inhibitors and the risk of malignancy: a meta-analysis across disease indications. Ann Rheum Dis. 2023 Aug;82(8):1059-1067.