Comparative cancer risk associated with methotrexate, other non-biologic and biologic disease-modifying anti-rheumatic drugs
Department of Orthopedics and Physical Rehabilitation; Department of Medicine, Division of Preventive and Behavioral Medicine
Clinical Epidemiology | Epidemiology | Musculoskeletal Diseases | Neoplasms | Rheumatology
OBJECTIVE: There is little information comparing the potential risk of cancer across conventional and biologic disease-modifying anti-rheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA). Methotrexate has not been the focus of most contemporary pharmacoepidemiologic studies of cancer.
METHODS: We conducted a comparative effectiveness study with cancer as the outcome. A large observational cohort of RA was followed up from 2001 to 2010. Reports of any cancer prompted a confirmation process that included adjudication of the primary cancer records. We used a propensity score (PS) with relevant covariates and cohort trimming to improve the balance between DMARD cohorts. Cox proportional hazard regression models were constructed to estimate the risk of cancer with various DMARDs, all compared with methotrexate.
RESULTS: We identified 6806 DMARD courses for analysis (1566 methotrexate; 904 nbDMARDs; 3761 TNF antagonists; 408 abatacept; and 167 rituximab). Non-biologic DMARDs (HR 0.17, 95% CI 0.05-0.65) and TNF antagonists (HR 0.29, 95% CI 0.05-0.65) were associated with a reduced adjusted risk of cancer compared with methotrexate. Abatacept (HR 1.55, 95% CI 0.40-5.97) and rituximab (HR 0.42, 95% CI 0.07-2.60) were similar in risk of cancer with methotrexate. These results were robust to sensitivity analyses. After controlling for DMARD exposures, risk factors for cancer included male gender, age, and alcohol consumption.
CONCLUSIONS: Cancer risk was elevated for methotrexate users compared with nbDMARDs and TNF antagonists.
Cancer, DMARDs, Epidemiology, Methotrexate, Rheumatoid arthritis
DOI of Published Version
Solomon DH, Kremer JM, Fisher M, Curtis JR, Furer V, Harrold LR, Hochberg MC, Reed G, Tsao P, Greenberg JD. Comparative cancer risk associated with methotrexate, other non-biologic and biologic disease-modifying anti-rheumatic drugs. Semin Arthritis Rheum. 2014 Feb;43(4):489-97. doi:10.1016/j.semarthrit.2013.08.003. Link to article on publisher's site
Seminars in arthritis and rheumatism
Solomon, Daniel H.; Kremer, Joel M.; Fisher, Mark; Curtis, Jeffrey R.; Furer, Victoria; Harrold, Leslie R.; Hochberg, Marc C.; Reed, George W.; Tsao, Peter; and Greenberg, Jeffrey D., "Comparative cancer risk associated with methotrexate, other non-biologic and biologic disease-modifying anti-rheumatic drugs" (2014). Orthopedics and Physical Rehabilitation Publications and Presentations. 159.