Background: The incidence of keratinocyte cancer (KC, largely comprised of basal cell carcinoma [BCC] and squamous cell carcinoma [SCC]) in the general population is increasing. Besides exposure to UV light, states of immune alteration have been linked to increased KC risk. Several studies from the pre-biologic era have linked rheumatoid arthritis (RA) with elevated risks of KC. The extent to which biologic or targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) modifies this increased risk of KC in RA remains uncertain. Besides the poorly characterized risk of KC overall in RA and with b/tsDMARDs, few studies have examined KC risk by subtype or assessed the risk of a second primary KC among patients with a prior KC who start b/tsDMARDs.

Objectives: To assess the risk of KC, overall and by subtype, in patients with RA initiating treatment with b/tsDMARDs, and to estimate the risk of a second KC in RA patients with history of KC who start a b/tsDMARD.

Methods: Nationwide cohort study of patients with RA who initiated a tumour necrosis factor inhibitor (TNFi), a non-TNFi bDMARD, or a janus kinase inhibitor (JAKi) between January 1 ^st 2012 and December 31 ^st 2021. Patients and treatments were assembled from the Swedish Rheumatology Quality Register (SRQ). Incident KC (and history of KC) were identified from linkage to the Cancer Register. Data of comorbid conditions were collected from the National Patient and Prescribed Drug Registers. We estimated adjusted hazard ratios (HRs) using Cox regression for the association between treatment group and the following outcomes: (1) KC overall, (2) SCC overall, (3) in-situ SCC, (4) invasive SCC, and (5) BCC, among patients without a history of KC at their b/tsDMARD treatment start, as well as (6) second KC among patients with a history of any KC at their b/tsDMARD treatment start. The treatment groups under study were; i) JAKi (baricitinib, filgotinib, tofacitinib, upadacitinib), ii) non-TNFi bDMARD (abatacept, rituximab, sarilumab, tocilizumab), and iii) TNFi (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab). We used TNFi as reference. The HRs were adjusted for age, sex, number of previously initiated b/tsDMARDs, comorbidities (diabetes, heart failure, ischemic heart disease, hospitalized infections, lung disease, kidney failure, joint surgery, organ transplantation, benign skin disorders), educational level, use of concomitant medications (csDMARD, oral steroids and topical steroids), RA disease-related factors (DAS28CRP, disease duration, seropositivity) and smoking status. We applied an ever-treated approach in which each individual was followed until any occurrence of the outcome, death, emigration from Sweden, or end of the study period (December 31 ^st 2021). Thus, one outcome (along with the person-time of follow-up during which it was diagnosed) could be attributed to more than one treatment.

Results: A total of 21,121 RA patients were identified. Of these, 2,300 initiated a JAKi, 6,316 a non-TNFi bDMARDs, and 12,502 a TNFi. Median (IQR) follow-up times were 2.5 (1.2 to 3.5) years for JAKi, 5.1 (2.8 to 7.3) years for non-TNFi bDMARD and 4.7 (2.5 to 7.2) years for TNFi. We identified 94 incident KCs with JAKi, 407 with non-TNFi, and 628 with TNFi b/tsDMARDs. Compared to TNFi, the HR for KC with JAKi was 1.72 (95% CI 1.02–2.87) and 0.81 (95% CI 0.60–1.07) for non-TNFi, Table 1. Among RA patients with a history of KC, the HR for a second KC was 2.76 (1.02–7.44) for JAKi vs TNFi and 1.54 (0.79–3.02) for non-TNFi vs TNF, Table 2.

Conclusion: This study suggests that patients with RA treated with JAKi have a higher incidence of a first ever KC, primarily driven by the BCC subtype. Additionally, although based on a limited number of events, we observed a higher incidence of a second KC in patients treated with JAKi compared to those treated with TNFi. Our findings support the notion that skin examination may benefit this population, and that skin cancer risks with JAKi treatment should be further monitored.

REFERENCES: NIL.

Acknowledgements: NIL.

Disclosure of Interests: Viking Huss: None declared, Hannah Bower: None declared, Karin Hellgren: None declared, Thomas Frisell: None declared, Johan Askling Abbvie, BMS, Eli Lilly, Galapagos, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi. Karolinska Institutet has entered into agreements with the following entities, with JA as PI, regarding the ARTIS national safety monitoring of rheumatology immunomodulators.

© 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.