Background: Melanoma is a highly immunogenic tumor which can activate immune responses capable of controlling its growth. Consequently, there have been concerns about the use of methotrexate (MTX) and/or tumor necrosis factor alpha inhibitors (TNFi) in patients with rheumatoid arthritis (RA) and concomitant melanoma, because of potential suppression of tumoral responses.

Objectives: To evaluate the association between use of these drugs and survival in patients with RA and early-stage concomitant melanoma in a population-based cohort of elderly patients.

Methods: We identified patients with RA and early-stage melanoma (in situ, localized, regional) from the Surveillance, Epidemiology, and End Results (SEER) linked to Medicare database. SEER is a cancer registry covering approximately 48% of the US population, and Medicare is a public health insurance plan covering 97% of the population 65 years and older. We included patients diagnosed with incident melanoma from January 1, 2008 to December 31, 2017 and follow-up with Medicare claims until 2019. We grouped patients according to the disease modifying antirheumatic treatment drugs (DMARD) received in the first year after melanoma diagnosis as follows: Group 1 - No DMARD received, or conventional DMARD other than MTX, or MTX < 6 months; Group 2 - Methotrexate ≥6 months without a biologic DMARD; and Group 3 - TNFi with or without conventional DMARD. We initially examined patients receiving TNFi alone, with MTX, or with other conventional DMARD, but as no differences were observed, TNFi use was analyzed as a single category. We excluded from the cohort patients receiving other biologics or targeted therapies as numbers were too small to analyze. Primary outcome was overall survival (OS). Analyses included Kaplan-Meier methods with log-rank tests and landmark analysis at year 1 with multivariable Cox proportional hazard models including propensity score adjustment. We estimated propensity scores for use of the drug of interest on the basis of patient demographics, year of diagnosis, comorbidity score, frailty, and cancer stage. Other variables in the model included cancer therapies in the year after melanoma diagnosis.

Results: We identified 455 patients with RA and early melanoma: 259 (57%) were female, mean age was 76±6 years, 217 (48%), 215 (47%) and 23 (5%) had in situ, localized and regional melanoma respectively. In the first year, 154 (34%) received MTX without a biologic DMARD (Group 2), and 99 (22%) received TNFi (Group 3). Median follow-up was 4.7 years (range 1-12 years). No significant differences were observed in OS among RA treatment groups, with 3-year survival ranging from 85% for patients in Group 1 to 93% in Group 3, and 5-year survival from 71% in Group 1 to 84% in Group 3 (p=0.07). Multivariable analysis with Cox regression showed no significant differences in mortality across groups (Table 1). Mortality was significantly increased in patients who received glucocorticoids in the first year after melanoma diagnosis at a mean prednisone-equivalent dose of >7.5 mg/day. As the cohort only included patients with early-stage melanoma, very few patients (5%) had received checkpoint inhibitors. Melanoma-specific mortality could not be adequately evaluated, as disease-specific survival at 5 years was 95%.

Conclusion: Treatment with MTX or TNFi in elderly patients with RA during the first year after a diagnosis of early-stage melanoma was not associated with increased mortality. In contrast, use of glucocorticoids during the same period was associated with shorter survival. Additional research is needed in younger populations, and in patients with more advanced melanoma.

REFERENCES: NIL.

Acknowledgements: Supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR078484), the National Cancer Institute (P30CA016672, K08CA263298) and the Cancer Prevention and Research Institute of Texas (RR190078).

Disclosure of Interests: Maria Suarez-Almazor SetPoint Medical Syneos Health, Novartis, Xiudong Lei: None declared, Juan Ruiz: None declared, Jennifer McQuade Merck, Bristol Myers Squibb Roche, Hui Zhao: None declared, Sharon Giordano: None declared, Isaac Weber: None declared, Mackenzie Wehner: 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.