Biologic Therapy for Rheumatoid Arthritis Linked to Skin Cancer Risk

August 29, 2007 — Biologic therapy for rheumatoid arthritis (RA) was associated with an increased risk for skin cancer but not for other types of cancers, according to an observational study published in the August 29 Online First issue and in the September print issue of Arthritis & Rheumatism.
"Induction of malignancy is a major concern when rheumatoid arthritis (RA) is treated with biologic therapy," write Frederick Wolfe, MD, and Kaleb Michaud, PhD, from the University of Kansas School of Medicine in Wichita. "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."
From 1998 to 2005, the authors studied incident cases of cancer in 13,001 patients who were observed for approximately 49,000 patient-years. Using the US National Cancer Institute Surveillance, Epidemiology, and End-Results (SEER) database, the investigators compared rates of cancer in the observational cohort vs those in the general population.
The risks for biologic therapy were evaluated with conditional logistic regression to calculate odds ratios (ORs) as estimates of the relative risk. Additional adjustments were made for 6 confounders: age, sex, educational level, smoking history, severity of RA, and use of prednisone.
Exposure to biologic therapy occurred in 49% of the study group. Incident cases of cancer included 623 cases of nonmelanotic skin cancer and 537 cases of other cancers.
Compared with the SEER data, the standardized incidence ratios were 1.0 for all cancers (95% confidence interval [CI], 1.0 - 1.1), 0.8 for breast cancer (95% CI, 0.6 - 0.9), 0.5 for colon cancer (95% CI, 0.4 - 0.6), 1.2 for lung cancer (95% CI, 1.0 - 1.4), and 1.7 for lymphoma (95% CI 1.3 - 2.2).
Although biologics were associated with an increased risk for nonmelanotic skin cancer (OR, 1.5; 95% CI, 1.2 - 1.8) and for melanoma (OR, 2.3; 95% CI, 0.9 - 5.4), no other cancer was associated with the use of biologic therapy. The overall risk for any cancer was 1.0 (95% CI, 0.8 - 1.2).
Limitations of the study include limited duration of biologic exposure; observational design; confounding by indication; and use of the National Death Index, which could have introduced possible bias.
"Biologic therapy is associated with increased risk for skin cancers, but not for solid tumors or lymphoproliferative malignancies," the study authors write. "These associations were consistent across different biologic therapies."
Abbott, Amgen, Bristol-Myers Squibb, Centocor, Merck, Pfizer, and Wyeth-Australia supported this study.
Arthr Rheum. Published online August 29, 2007.2007;56:2886-2895.