Tumor necrosis factor α antagonist use and cancer in patients with rheumatoid arthritis

Abstract

Objective. Concerns persist about a possible association between tumor necrosis factor ␣ (TNF␣) antagonist treatment and development of cancers in patients with rheumatoid arthritis (RA). This study was undertaken to estimate the association between treatment with biologic disease-modifying antirheumatic drugs (DMARDs) and development of cancer in patients with RA.Methods. We conducted a cohort study pooling administrative databases from 2 US states and 1 Canadian province. A cohort of patients who had received a diagnosis of RA on >1 occasion and had been prescribed DMARDs was identified. We categorized patients with a prescription for a biologic DMARD as biologic DMARD users, and those with a prescription for methotrexate (MTX) but no biologic DMARD as MTX users. We used time-varying propensity scores to adjust for the large number of possible confounders and stratified proportional hazards regression to estimate the effects of biologic DMARDs on cancer. The primary end points were hematologic malignancies (lymphoma, multiple myeloma, and leukemia) and common solid tumors (colorectal, lung, stomach, breast, prostate, uterine, ovarian, urinary tract/bladder, and melanoma).

TNFα blockade in human diseases: An overview of efficacy and safety

“…Solid tumors-Studies of TNFα antagonist therapy in RA reveal no increased risk of solid tumors compared to the general population [99,102], corroborating results reported by the FDA. In contrast, a recent meta-analysis [82] reported higher rates of malignancies in RA patients treated with anti-TNF agents (29 of 3493 or 0.8%) compared to those on either placebo or active controls (3 of 1512 or 0.2%).…”

“…Several reports have evaluated the risk of lymphoma in patients treated with TNFα blockers [91,98,99]. Standardized incidence ratio (SIR) values vary from 2.6 to 11.5 in anti-TNF-treated groups compared to the general population.…”

“…One study that compared the rate of lymphoma in TNF-treated RA patients to a control RA group found no increased risk [100]. A recent cohort study of 1152 biologic users and 7306 MTX users from 2 US states and 1 Canadian province [99] demonstrated a propensity score-adjusted pooled hazard ratio was 1.37 (95% CI 0.71-2.65) for hematologic malignancies and 0.91 (95% CI 0.65-1.26) for solid tumors, which does not support the likelihood of increased risk of malignancies by the use of biologic agents compared to MTX.…”

Autoimmune Disorders and Lymphomas

“…The use of biologic drugs as antagonists of TNF has been extensively evaluated for safety profile both in randomized (Bongartz et al, 2006, Leombruno et al, 2009) and observational studies (Wolfe & Michaud, 2007, Setoguchi et al, 2006. TNF plays an important role in tumour growth control and host defence, and biologic therapy targeting TNF determines an important immunomodulation, raising thus the concern of a possible increased risk of malignancies in patients treated with anti-TNF antibodies.…”

“…A cohort study using patients with RA treated with methotrexate (MTX) as a control group did not show any significant increase in the risk of cancer in biologic DMARDS users. This particular control group has been chosen because of similar disease severity between patients treated with these two strategies, and investigators have concluded that it is unlikely that RA patients who have received biologic agents have a greater risk of lymphoproliferative disorders compared with those treated with MTX (Setoguchi et al, 2006). A single observational study has reported relative risk for cancer occurrence per single anti-TNF agent (infliximab, etanercept, adalimumab), finding a positive association between biologic therapy and skin cancers, but not with other malignancies, with a median time of exposure of 3.0 years, for any of the three agents separately.…”