Hurdles in new drug development in rheumatic diseases

•Disease control is not achieved by a proportion of rheumatic disease patients.•Diversity in underlying disease processes may be the reason for the treatment gap.•Trial designs with appropriate outcomes and diverse patient populations are needed.•Continued focus on innovation can overcome these challenges. Rheumatic diseases are heterogenous conditions with multifactorial underlying physiologic pathogeneses. Despite recent progress in the identification and development of advanced therapies primarily focusing on disrupting the immunological abnormalities that cause these conditions, rheumatic disease management remains challenging in a notable proportion of patients, with many exhibiting uncontrolled or refractory disease activity. New and improved therapies are needed to respond to this treatment gap. However, there are important hurdles that can affect the expedited identification and assessment of new treatments. We present a review of key hurdles in the development of antirheumatic agents, as well as possible solutions to these obstacles. We highlight the challenges presented by incomplete understanding of the complexity of rheumatic disease pathophysiology and the resultant difficulties in the identification, development, and evaluation of new therapies. We further explore the diversity of the underlying disease processes leading to heterogeneity in patient response to treatment, necessitating the re-design of clinical trials of antirheumatic agents to detect efficacy signals and better inform clinical disease management. Finally, emergent strategies and methodologies with potential to improve upon these hurdles are presented. New and modified study designs and research tools that leverage ongoing advancements in the elucidation of rheumatic disease pathogenesis coupled with progress in methods to mine available data will be instrumental in overcoming current hurdles in antirheumatic drug development.