Tumor necrosis factor inhibitors and the risk of cancer among older Americans with rheumatoid arthritis

Background: TNF inhibitors (TNFi) effectively treat rheumatoid arthritis but may increase patient risk of some malignancies, particularly lymphomas or skin cancers. Methods: We used Surveillance, Epidemiology, and End Results (SEER)-Medicare data to conduct a case-control study in patients with rheumatoid arthritis (2007-2015). Cases were individuals with a first cancer diagnosed in SEER registries (ages 66-99, 22 cancer sites, N ¼ 10,263). Skin cancer cases [nonmelanoma skin cancer (NMSC, N ¼ 501), basal cell carcinoma (BCC, N ¼ 161), squamous cell carcinoma (SCC, N ¼ 150)] and cancer-free controls (N ¼ 30,475) were selected from Medicare beneficiaries residing in SEER areas. Cases and controls had prior Medicare claims-based evidence for rheumatoid arthritis, and TNFi exposure was ascertained from part B and part D claims. Logistic regression was used to estimate adjusted odds ratios (aOR). Results: TNFi exposure was present in 16.2% of controls and 12.8% to 33.7% of cancer cases, varying by site. TNFi use was associated with increased risk of NMSC overall (aOR 1.32, 95% confidence interval 1.06-1.63), non-Hodgkin lymphoma (NHL) overall (1.28, 1.06-1.56) and, specifically, follicular lymphoma (2.63, 1.63-4.24). TNFi exposure was not associated with other SEER cancer sites, BCC or SCC specifically, or other common NHL subtypes. Conclusions: Among older adults with rheumatoid arthritis, TNFi exposure was associated with elevated risk of NMSC and NHL, driven specifically by follicular lymphoma. Exposure was not associated with increased risk for other cancer sites. Impact: Our results support a role for TNF in lymphomagenesis. Given the association with NMSC, patients initiating TNFi therapy may benefit from skin cancer screening and sun protection measures.