Background: Janus kinase inhibitors (JAKi) have demonstrated significant efficacy in the treatment of rheumatoid arthritis (RA). Tofacitinib, a first-generation JAKi targeting JAK1 and JAK3, has been reported to carry a higher malignancy risk compared to TNF-α inhibitors (TNFi) in RA patients aged 50 and older with at least one cardiovascular risk factor [1]. However, its effect on malignancy risk in Asian patients with high disease activity remains unclear.

Objectives: This study aimed to assess the incidence of malignancies and identify associated risk factors in Asian RA patients receiving JAKi, conventional synthetic DMARDs (csDMARDs), biological DMARDs (bDMARDs).

Methods: We retrospectively evaluated 3,804 patients with RA between 2001 and 2023. Patients with missing data or a history of prior cancer diagnosis were excluded. JAKi included tofacitinib, baricitinib, and upadacitinib. bDMARDs included TNFi, anti-IL-6 receptor monoclonal antibody (tocilizumab), cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4)-immunoglobulin (Ig) fusion protein (abatacept), and B-cell-depleting agents (anti-CD20 monoclonal antibody, rituximab). A time-dependent model was used to assess medication changes. JAKi and bDMARDs were only prescribed to subjects who were refractory to csDMARD therapy for over 6 months, as defined by Taiwan National Health Insurance.

Results: During the 20,759 patient-years (PYs) of follow-up, a total of 161 of 2,904 patients (5.54 %) developed cancer, resulting in a crude incidence of malignancy of 7.76 events per 1000 PYs. Among the 161 patients with malignancy events, breast cancer was the most common (N = 29), followed by gastrointestinal tract cancer (N = 24), hematopoietic malignancies (N = 23), lung cancer (N = 21), colorectal cancer (N = 15) and renal/urinary tract cancer (N = 13). Among patients treated with tofacitinib, 14 malignancies occurred over 1,807 PYs, with an incidence rate of 7.75 per 1,000 PYs, which was lower than the incidence observed with TNFi (10.13 per 1,000 PYs), where 27 new cancer cases were reported over 2,665 PYs. Notably, older patients (aged over 65 years) receiving tofacitinib appeared to have a higher hazard of overall malignancies compared to those treated with TNFi; however, this difference did not reach statistical significance (adjusted HR: 2.56, 95% CI: 0.57–11.47, p = 0.218). In the multivariable model, a higher baseline erythrocyte sedimentation rate was a significant risk factor for malignancy (aHR: 1.67. 95% CI: 1.02–2.75, p = 0.042).

Conclusion: The results indicate no statistically significant difference in malignancy risk between Asian RA patients treated with tofacitinib and those receiving TNFi. Nonetheless, regular cancer screenings remain essential for patients undergoing JAKi or biologic therapy to ensure early detection and management.

REFERENCES: [1] Ytterberg SR, Bhatt DL, Mikuls TR, Koch GG, Fleischmann R, Rivas JL, Germino R, Menon S, Sun Y, Wang C, Shapiro AB, Kanik KS, Connell CA; ORAL Surveillance Investigators. N Engl J Med. 2022 Jan 27;386(4):316-326.

Acknowledgements: NIL.

Disclosure of Interests: None declared.

© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.