Background Concerns regarding the risk of cancer with janus kinase inhibitor (JAKi) use in patients with rheumatoid arthritis (RA) escalated after the release of results from Pfizer’s clinical trial, ORAL Surveillance.^[1] The trial showed increased risks of major adverse cardiovascular events and cancer in tofacitinib compared with tumour necrosis factor inhibitor recipients. Precautionary considerations on JAKi use in high-risk subsets of patients with RA have since been issued by the European Medicines Agency.

Objectives We aimed to investigate the risk of first primary cancer in patients with RA treated JAKi (tofacitinib and baricitinib) compared with those who received biologic disease-modifying anti-rheumatic drugs (bDMARDs) in a real-world setting.

Methods We performed an observational cohort study using the nationwide registers in Denmark. Patients with RA aged 18+ years, without a previous cancer diagnosis, and who initiated treatment with JAKi or bDMARDs from 1 January 2017 to 31 December 2020 were identified in the Danish Rheumatology Quality Register (DANBIO) and followed for any cancer (except non-melanoma skin cancer). We applied inverse probability of treatment weighting (IPTW) to account for covariate differences between treatment groups. IPTW-generated weights were used with cause-specific Cox (CSC) models to calculate hazard ratios (HRs) for cancer incidence in JAKi-treated compared with bDMARD-treated patients with RA. Multiple subgroup and sensitivity analyses were performed.

Results We identified 875 and 4247 RA patients treated with JAKi and bDMARDs, respectively. The JAKi group contributed with 1315 person years (PYRS) and 19 cancers, while the bDMARD group contributed with 8597 PYRS and 111 cancers. The corresponding crude incidence rates per 1000 PYRS for cancer were 14.4 (JAKi) and 12.9 (bDMARD). Comparing the two groups using weighted CSC models, a HR of 1.41 (95%CI 0.76 to 2.37, 95% confidence intervals) was seen for JAKi- versus bDMARD-treated patients with RA.

Conclusion JAKi treatment in real-world patients with RA was not associated with a statistically significant increased risk of first primary cancer compared with those who received bDMARDs. However, risk estimates were elevated in many analyses, and an excess risk of cancer with JAKi treatment cannot be ruled out. More studies investigating JAKi and cancer risk in patients with RA are highly warranted.

Reference [1]Ytterberg SR, Bhatt DL, Mikuls TR, et al. Cardiovascular and Cancer Risk with Tofacitinib in Rheumatoid Arthritis. N Engl J Med 2022; 386: 316-326. 2022/01/27. DOI: 10.1056/NEJMoa2109927.

Acknowledgements The authors wish to extend our thanks to all Danish departments of rheumatology for reporting and contributing to the DANBIO register.

The study was financially supported by the Danish Rheumatism Association and the Danish Cancer Society. The funders were involved neither in the planning, performance, nor the submission of the abstract.

Disclosure of Interests Rasmus Westermann: None declared, René Lindholm Cordtz: None declared, Kirsten Duch: None declared, Lene Mellemkjær Shareholder of: Have an immediate family member who owns stocks in Novo Nordisk., Employee of: Have an immediate family member who is employed at Novo Nordisk., Merete Lund Hetland Speakers bureau: Pfizer, Medac, Sandoz.

No personal income. Paid to my institution., Grant/research support from: AbbVie, Biogen, BMS, Celtrion, Eli Lilly Denmark A/S, Janssen Biologics B.V, Lundbeck Fonden, MSD, Novartis, Pfizer, Roche, Samsung Biopis, Sandoz: No personal income. Paid to my institution.

MLH has chaired the steering committee of the Danish Rheumatology Quality Registry (DANBIO, DRQ), which receives public funding from the hospital owners and funding from pharmaceutical companies. MLH co-chairs EuroSpA, which generates real-world evidence of treatment of psoriatic arthritis and axial spondylorthritis based on secondary data and is partly funded by Novartis., Andrea Michelle Burden: None declared, Ole Hejlesen: None declared, Martin Bøgsted: None declared, Lene Dreyer Grant/research support from: BMS: Reports of safety. Grant to our institution.

Member of the Steering comity of the national DANBIO database for 6 years, which receives public funding from the hospital owners and funding from pharmaceutical companies.