Biologic agents in rheumatology: unmet issues after 200 trials and $200 billion sales

Key PointsThe market for biologic therapies for rheumatic diseases is large, with sales totalling over $200 billion to date; however, their popularity is not justified by the available evidenceThe clinical trial evidence relating to biologic agents used to treat rheumatic diseases has several shortcomings that prevent optimal implementation of these agents in clinical practice and complicate regulatory decision makingA paucity of head-to-head comparisons, limited follow-up times, variations in outcome definitions and nomenclature, and non-publication of trials and outcomes limit our understanding of biologic agentsMost trials are pharmaceutical-industry-sponsored, and have short follow-up periods and small sample sizes, which restrict our interpretation of the clinical relevance of the findings with regard to long-term disease outcomesThe lack of long-term randomized trials of biologic agents has limited our understanding of the association of these drugs with adverse events, particularly the risk of malignancies and serious infectionsLarger study populations, longer follow-up times, better reporting and head-to-head comparisons of biologic agents would increase knowledge of the benefits and risks associated with the different treatments available