TY - JOUR T1 - Evaluating the Real-world Benefits and Risks of Anti-Tumor Necrosis Factor Therapies JF - The Journal of Rheumatology JO - J Rheumatol SP - 4 LP - 6 DO - 10.3899/jrheum.121260 VL - 40 IS - 1 AU - AUDREY LOW AU - KIMME HYRICH Y1 - 2013/01/01 UR - http://www.jrheum.org/content/40/1/4.abstract N2 - The discovery of tumor necrosis factor-α (TNF-α) as the pivotal cytokine in the inflammatory pathway and the development of drugs specifically targeted at this molecule has revolutionized our treatment of patients with rheumatoid arthritis (RA) and other inflammatory arthritides over the past decade. Trial after trial, investigators have consistently demonstrated efficacy in reducing disease activity, inflammation, and radiographic progression with anti-TNF therapy1. However, questions remain regarding the longterm safety of anti-TNF therapy because of the pleiotropic effects of TNF-α in immune system regulation. Such questions cannot always be answered in the context of a randomized controlled trial (RCT). By its very nature, an RCT is an experiment, an attempt to replicate a controlled laboratory environment using a homogeneous population of study subjects, with preset questions. This limits the generalizability of the results to the wider population of patients we see in routine clinical practice2. Also, some questions, especially about longterm safety, cannot always be answered because the duration of an RCT is relatively short. Observational studies can go some way toward answering these pertinent questions.Over the past decade, a number of biologic registers and other observational studies of “real-world” anti-TNF use have been established and have started to address important questions regarding treatment benefits3,4, longterm treatment persistence5, and safety, with a focus on serious infections6,7,8 and malignancy9,10,11. Many of these studies have been based in large healthcare claims databases, which gather details about patient interactions with the healthcare system12. These studies have the advantage of large sample sizes but can be limited in the detail … Address correspondence to Dr. Hyrich; E-mail: kimme.hyrich{at}manchester.ac.uk ER -