Study Finds No Overall Cancer Risk With JAK Inhibitors in RA, But Lung Cancer Risk Elevated in Older Adults
A large population-based case–control study using SEER-Medicare data found that Janus kinase inhibitors (JAKis) are not associated with an increased overall cancer risk in older adults with rheumatoid arthritis (RA). However, JAKi use was linked to a significantly elevated risk of lung cancer, particularly in men and in those with longer exposure durations. These findings provide important safety data for clinicians managing RA in older populations.
The study included 12,463 patients with RA aged 65 years or older with a first cancer diagnosis between 2014 and 2019, and 38,345 cancer-free controls. All participants were drawn from the SEER-Medicare database. Drug exposure was determined from prescription claims for JAKis, tumor necrosis factor inhibitors (TNFis), and other biologic DMARDs (bDMARDs).
Overall cancer risk was not significantly associated with any of the therapeutic classes studied. The adjusted odds ratio (OR) for cancer among JAKi users was 1.04 (95% CI 0.87–1.26), while TNFis and other bDMARDs had ORs of 0.98 (95% CI 0.92–1.05) and 0.98 (95% CI 0.90–1.07), respectively.
“Among older adults with RA, JAKi exposure over a median of 1.8 years was not associated with an overall increase in cancer risk,” the authors wrote.
Despite the reassuring overall cancer risk profile, the study identified a notable signal for lung cancer. JAKi exposure was associated with a significantly increased risk of lung cancer, with an OR of 1.40 (95% CI 1.06–1.87). The risk was more pronounced in males (OR 2.12, 95% CI 1.14–3.94) and in patients with more than two years of documented JAKi exposure (OR 1.52, 95% CI 1.01–2.28).
“These findings support clinical caution in prescribing this medication class to smokers,” the authors concluded, referencing the well-established link between smoking and lung cancer risk.
Interestingly, the study also found a reduced risk of breast cancer among female JAKi users. The adjusted OR for breast cancer in this subgroup was 0.62 (95% CI 0.39–0.97), though the clinical significance of this observation requires further investigation.
For practicing rheumatologists, the key takeaway is that JAKis appear to have a neutral effect on overall cancer risk in older patients with RA but may increase lung cancer risk in select populations. This information is particularly relevant for long-term treatment planning in patients with risk factors such as smoking history or chronic pulmonary disease.
Clinicians should continue to evaluate cancer risk on an individual basis and consider patient-specific factors such as age, sex, smoking status, and cumulative drug exposure. The study emphasizes the need for further research into the JAK/STAT signaling pathway and its potential mechanistic links to carcinogenesis.
These findings offer additional context for shared decision-making around JAKi initiation, especially in older patients with RA where safety concerns may guide therapy selection.
Reference
Ahmed S, Pfeiffer RM, Jackson SS, et al. Cancer risk of Janus kinase inhibitors and biological disease-modifying antirheumatic drugs among older Americans with rheumatoid arthritis. Lara D Veeken. February 2025. doi:10.1093/rheumatology/keaf092
