BOSTON, Mass–Clinicians concerned that patients with rheumatoid arthritis (RA) treated with tumor necrosis factor (TNF) inhibitors might have an increased cancer risk may be reassured by data from Soko Setoguchi, MD, and colleagues showing that patients treated with these agents have about the same cancer risk as those treated with methotrexate (MTX), once the severity of the underlying RA is accounted for. The cohort study of 1152 patients treated with biologics and 7306 treated with MTX is published in the September issue of Arthritis & Rheumatism.¹

"Our study indicated that users of TNF-α antagonists have similar risks for cancers as do users of MTX after adjusting for those factors [that] appeared to be associated with RA severity. However, small increase or decrease in risk cannot be excluded," Dr. Setoguchi told CIAOMed.

Differences in RA Severity Change Cancer Risk

Several previous studies had raised the issue of increased cancer risk, most prominently a review by Wolfe and Michaud that found a 2- to 4-times increased lymphoma incidence in RA patients treated with TNF inhibitors compared with the general population.²

"The increased risk in biologics users in that study could be explained by the difference in the underlying characteristics and risk among their study patients (treated exclusively by rheumatologists) compared with our study patients (many of whom were not treated by rheumatologists). Wolfe et al did not adjust for patient characteristics other than age and gender, whereas our models adjusted for a broader range of variables," Dr. Setoguchi said.

Dr. Soko and colleagues at Harvard Medical School (Boston) and at the University of British Columbia (Vancouver) pooled administrative databases from two US states and one Canadian province to identify a cohort of patients who had received a diagnosis of RA on one or more occasions and had been prescribed disease-modifying antirheumatic drugs (DMARDs). They compared patients who had been prescribed a "biologic DMARD" with those prescribed only MTX (n = 7306). The biologic DMARD group (n = 1152) included patients who had taken etanercept (Enbrel®, n = 743), infliximab (Remicade®, n = 381), adalimumab (Humira®, n = 0), or anakinra (Kineret®, n = 28). The primary study endpoints were hematologic malignancies (lymphoma, multiple myeloma, or leukemia) and common solid tumors (colorectal, lung, stomach, breast, prostate, uterine, ovarian, urinary tract/bladder, or melanoma).

The patients prescribed biologic DMARDs tended to have more severe manifestations of RA (Table). To control for confounding by indication due to RA severity, researchers developed a propensity score that varied with time. They also used a Cox proportional hazards model to adjust hazard ratios for a number of possible confounders.

Table. Rheumatoid Arthritis Severity-Related Variables in Biologic DMARD vs MTX Treatment Groups