Anti-TNF Therapy and Solid Cancer Risk

Chicago—Patients treated with anti–tumor necrosis factor (TNF) therapy for rheumatoid arthritis (RA) are not at increased risk of solid cancers compared with patients receiving nonbiologic disease-modifying antirheumatic drugs (DMARDs), investigators reported in a study presented in an oral abstract session and at a news conference at the ACR meeting. “Anti-TNF therapy does not appear to increase the risk of cancer in solid organs above that seen with traditional DMARD therapy over the first 5 years of therapy,” said lead author of the study, Kimme L. Hyrich, Arthritis Research UK Epidemiology Unit, University of Manchester, Manchester, United Kingdom, who presented the results. Despite the current published evidence that shows a lack of association between an increased risk of solid cancers and anti-TNF therapy, investigators from the Arthritis Research UK Epidemiology Unit at the University of Manchester further examined a possible association because of the short duration and strict criteria of the current published evidence that could have missed latent events such as cancer. The investigators used data from the British Society for Rheumatology Biologics Register, a registry that tracks the progress of patients with severe RA and other rheumatic diseases who are taking anti-TNF therapy, to determine whether anti-TNF therapy influences the risk of cancer when used in routine UK practice. The study included 2 cohorts of patients receiving therapy for RA between 2001 and 2009. One cohort included patients receiving anti-TNF therapy (n=11,719) with etanercept (n=4072), infliximab (n=3429), or adalimumab (n=4218). The second cohort included those who never received anti-TNF therapy and were on DMARDs (n=3543). The analysis excluded the first 6 years of follow-up for each patient. Patients with a history of a solid cancer prior to registration were excluded. Patients from both cohorts were followed for 5 years, until December 2009 or death. Incident cancers were identified by lifelong flagging with the UK’s National Health Service-Information Center, 6 monthly patient and physician questionnaires for 3 years, and annual physician questionnaires thereafter. Analysis only included the first solid cancer per patient, excluding nonmelanoma skin cancer. Cancers that occurred after ending anti-TNF therapy were attributed to the most recent anti-TNF agent used. To compare the rates of solid cancer in the anti-TNF cohort and DMARD cohort, multivariate Cox proportional hazards models were used and adjusted for age, sex, comorbidity, disease duration, use of nonsteroidal anti-inflammatory drugs, smoking, and year of registration. In each cohort, site-specific analyses were performed for sites (colorectal, lung/bronchus, and female breast) with ≥10 cancers. The study found 386 solid cancers, 295 in patients treated with anti-TNF therapy and 91 in those treated with DMARDs. Multivariate analysis found no difference between the cohorts in the risk of solid cancer, with a hazard ratio (HR) for anti-TNF therapy of 0.88. The HRs for the individual anti-TNF agents were 0.94 for etanercept, 0.87 for infliximab, and 0.81 for adalimumab. Site-specific analysis also did not find any differences between the cohorts in the risk of colorectal, lung/bronchus, or female breast cancer, and no variation in the risk was found with duration of follow-up. These results show no difference in solid cancer risk between patients treated with anti-TNF and DMARDs therapy for RA. However, the authors reiterated the need for longer follow-up. “As cancer can be a latent effect, continued observation of these patients will be very important,” Dr. Hyrich said.