001) were significantly and independently associated with drug withdrawal in patients treated with IFX, ETN or ADA. Regarding individual rheumatic diseases, a diagnosis of RA had the highest HR for drug withdrawal (HR

1.49 [1.24–1.78]; P = 0.001), whereas a diagnosis of SpA was most favorable for drug retention (HR 0.67 [0.53–0.85]; P < 0.001), after adjustment for age, sex, disease duration and the choice of the anti-TNFα agent (Table 5). Worldwide registries on the use of biologics in the treatment of rheumatic diseases have provided valuable data on their long-term efficacy and safety.[11-17] Such information cannot be provided by randomized controlled SCH 900776 cost trials (RCTs) of the biological agents because of the following reasons.[18] First, the duration of RCTs is generally limited and not long enough to study the long-term efficacy or safety end points of the biological agents, particularly complications that

take a long time to develop, such as malignancies, cardiovascular complications and mortality. This limitation cannot be resolved by meta-analyses of the RCTs because of the short duration of follow-up. Even if an extended observation phase is available in some studies, the open-label nature is limited by bias for patient selection and the lack of a comparison group. Second, as head-to-head comparison of the biological agents is seldom the focus of RCTs, information Thymidylate synthase on the relative efficacy and safety of the biological agents is often GW572016 unclear. Third, RCTs typically exclude patients with active co-morbidities who may be at higher risk of development of toxicities related to the use of the biological agents. Thus, information on the

toxicities of these agents on high-risk patients cannot be reflected by these studies. Post-marketing surveillance reports, case series on uncommon toxic effects and mandatory information submitted to regulatory agents can be a useful source of information on specific safety signals but rarely provide accurate data on the true incidence of a certain adverse event. This is because the denominator of patients treated is usually unclear and reporting is purely on a voluntary basis.[18] As a result, the most useful data are derived from large national registries, such as the UK’s British Society for Rheumatology Biologics Registry (BSRBR), Sweden’s Anti-rheumatic Therapies in Sweden (ARTIS), Germany’s Rheumatoid Arthritis Observation of Biologic Therapy (RABBIT), Denmark’s DANBIO registry, France’s Research Axed on Tolerance of Biotherapies (RATIO) registry, Spain’s BIOBADASER and North America’s Consortium of Rheumatology Researchers of North America (CORONNA) registry.[11-17] These registries are able to include a large cohort of real-world patients for a long period of time so that risk related to individual diagnosis and biological agent can be estimated.