Biologic treatment of rheumatoid arthritis and the risk of malignancy: Analyses from a large US observational study


  • During the period of data collection, the National Data Bank for Rheumatic Diseases received research support from Abbott, Amgen, Bristol-Myers Squibb, Centocor, Merck, Pfizer, and Wyeth-Australia.



Induction of malignancy is a major concern when rheumatoid arthritis (RA) is treated with biologic therapy. A meta-analysis of RA biologic clinical trials found a general increased risk of malignancy, but this risk was not found in a large observational study. We undertook this study to assess the risk of malignancy among biologic-treated patients in a large US observational database.


We studied incident cases of cancer among 13,001 patients during ∼49,000 patient-years of observation in the years 1998–2005. Cancer rates were compared with population rates using the US National Cancer Institute SEER (Surveillance, Epidemiology, and End-Results) database. Assessment of the risk of biologic therapy utilized conditional logistic regression to calculate odds ratios (ORs) as estimates of the relative risk, further adjusted for 6 confounders: age, sex, education level, smoking history, RA severity, and prednisone use.


Biologic exposure was 49%. There were 623 incident cases of nonmelanotic skin cancer and 537 other cancers. The standardized incidence ratios and 95% confidence intervals (95% CIs) compared with SEER data were as follows: all cancers 1.0 (1.0–1.1), breast 0.8 (0.6–0.9), colon 0.5 (0.4–0.6), lung 1.2 (1.0–1.4), lymphoma 1.7 (1.3–2.2). Biologics were associated with an increased risk of nonmelanotic skin cancer (OR 1.5, 95% CI 1.2–1.8) and melanoma (OR 2.3, 95% CI 0.9–5.4). No other malignancy was associated with biologic use; the OR (overall risk) of any cancer was 1.0 (95% CI 0.8–1.2).


Biologic therapy is associated with increased risk for skin cancers, but not for solid tumors or lymphoproliferative malignancies. These associations were consistent across different biologic therapies.