Background: Regulatory authorities issued precautionary recommendations on the use of Janus kinase inhibitors (JAKi) following the ORAL Surveillance trial [1], which demonstrated an elevated risk of cancer with tofacitinib, compared to TNF inhibitors (TNFi). While these findings have influenced clinical guidance, there is still limited real-world evidence on malignancy risks associated with JAKi treatment.

Objectives: To assess the incidence of cancer in rheumatoid arthritis (RA) patients treated with JAKi, compared to other biologic disease modifying anti-rheumatic drugs (bDMARDs), using data from a large, multi-country, real-world population.

Methods: We studied patients from 13 RA registers across Europe and Québec, starting JAKi, TNFi -inhibitors (TNFi) or bDMARDs with other modes of action (OMA). Outcomes of interest were categorized into cancer excluding non-melanoma skin cancer (NMSC); and NMSC cases. Cancers were linked to treatments within 5 years of cessation or until follow-up loss, death, or study end, whichever came first. Incidence rates (IR) per 100 patient-years (PY) with 95% confidence intervals (CI) were computed. Poisson regression, with propensity score weighting (including country, disease-, and patient-characteristics, and comorbidities, see Figure 1), was used to obtain adjusted incidence rate ratios (aIRR), with 95% CI. A sub-analysis was performed on patients aged ≥ 50 years and ≥ 1 cardiovascular risk factor, mimicking the “ORAL Surveillance” trial inclusion criteria (high risk cohort).

Results: Over the 53’169 treatment initiations considered in 33’127 patients, 638 cancers excluding NMSC and 219 NMSC were reported. Crude incidence of cancer excluding NMSC was lower for TNFi (2.2/1000 PY) than for JAKi (2.9/1000 PY) and OMA (3.1/1000 PY). The adjusted Poisson regression found no significant difference in the incidence of cancer excluding NMSC (aIRR = 1.10; 95% CI [0.89; 1.37]) or NMSC (aIRR = 1.12; 95% CI [0.78; 1.60]) between JAKi and TNFi, nor between JAKi and OMA (aIRR = 1.07; 95% CI [0.86; 1.32] and aIRR = 0.79; 95% CI [0.54; 1.15] respectively). The high risk cohort accounted for 39.4% of treatment courses and had a higher incidence of cancer in each treatment group (OMA: 4.1/1000 PY, JAKi: 4.2/1000 PY, TNFi: 3.2/1000 PY). Similarly to the overall population, no significant difference in the incidence of cancer excluding NMSC (aIRR = 1.16; 95% CI [0.86; 1.57]) and NMSC (aIRR = 1.15; 95% CI [0.71; 1.84]) was observed between JAKi and TNFi, nor between JAKi and OMA (aIRR = 1.09; 95% CI [0.81; 1.47] and aIRR = 0.92; 95% CI [0.58; 1.46] respectively).

Conclusion: In this real-world study, including 13 RA registers and all currently available JAKi, we did not find a significantly higher risk of cancer excluding NMSC or of NMSC in RA patients treated with JAKi compared to bDMARDs (TNFi or OMA). Further analyses are planned, including the inclusion of additional registries to enhance statistical power and the evaluation of incidence across different exposure periods.

REFERENCES: [1] DOI:10.1056/NEJMoa2109927

Figure 1.

Acknowledgements: This study is investigator initiated. The JAK-pot collaboration is supported by unconditional/unrestricted research grants from AbbVie Inc., Eli Lilly and Co., and Alfasigma S.p.A. and was previously supported by Pfizer Inc and Galapagos NV.

Disclosure of Interests: Romain Aymon: None declared, Denis Mongin: None declared, Benoit Gilbert: None declared, Romain Guemara: None declared, Denis Choquette: None declared, Catalin Codreanu: None declared, Louis Coupal: None declared, Irini Flouri: None declared, Ruth Fritsch-Stork: None declared, Roberto Giacomelli: None declared, Doreen Huschek: None declared, Florenzo Iannone Abbvie, Galapagos, Eli-Lilly, Pfizer, UCB, Abbvie, Janssen, UCB, Galapagos, Tore K. Kvien Grünenthal, Janssen, Sandoz, AbbVie, Gilead, Janssen, Novartis, Pfizer, Sandoz, UCB, AbbVie,BMS, Galapagos, Novartis, Pfizer, UCB, Lucía Otero-Varela: None declared, Dan Nordström MSD, Novartis, Pfizer, UCB, Karel Pavelka AbbVie, Eli Lilly, Sandoz, UCB, Medac, Pfizer, Manuel Pombo-Suarez: None declared, Sella Aarrestad Provan: None declared, Ziga Rotar Abbvie, Amgen, AstraZeneca, Boehringer, Biogen, Eli Lilly, Janssen, Medis, MSD, Novartis, Pfizer, Sandoz Lek, Stada, SOBI, Abbvie, AstraZeneca, Boehringer, Eli Lilly, Janssen, Medis, MSD, Novartis, Pfizer, Sandoz Lek, SOBI, Prodromos Sidiropoulos: None declared, Elsa Vieira-Sousa: None declared, Anja Strangfeld AbbVie, Galapagos, Lilly, Pfizer, Takeda, UCB, Unconditional grant to my institution for the RABBIT register with equal parts from AbbVie, Amgen, BMS, Celltrion, Fresenius Kabi, Galapagos, Hexal, Lilly, MSD, Viatris, Pfizer, Roche, Samsung Bioepis, Sanofi-Aventis, and UCB, Jakub Závada Abbvie, Elli-Lilly, Sandoz, Novartis, Egis, UCB, Sanofi, AstraZeneca, Sobi, Abbvie, Novartis, AstraZeneca, Glaxo, Delphine Sophie Courvoisier: None declared, Axel Finckh AbbVie, Astra Zeneca, Eli-Lilly, Pfizer, UCB, AbbVie, Alfasigma, Eli-Lilly, Galapagos, Pfizer, Kim Lauper Pfizer.

© 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.