The Development of Disease-Modifying Therapies for Osteoarthritis (DMOADs): The Evidence to Date

Osteoarthritis (OA) is a complex heterogeneous articular disease with multiple joint tissue involvement of varying severity and no regulatory-agency-approved disease modifying drugs (DMOADs). In this review, we discuss the reasons necessitating the development of DMOADs for OA management, the classifications of clinical phenotypes or molecular/mechanistic endotypes from the viewpoint of targeted drug discovery, and then summarize the efficacy and safety profile of a range of targeted drugs in Phase 2 and 3 clinical trials directed to cartilage-driven, bone-driven, and inflammation-driven endotypes. Finally, we briefly put forward the reasons for failures in OA clinical trials and possible steps to overcome these barriers.

Automated summary

This review discusses the need for disease modifying drugs (DMOADs) for the management of osteoarthritis (OA), the classification of clinical phenotypes or molecular/mechanistic endotypes for targeted drug discovery, and summarizes the efficacy and safety of targeted drugs in Phase 2 and 3 clinical trials targeting cartilage-driven, bone-driven, and inflammation-driven endotypes. The reasons for failures in OA clinical trials and possible steps to overcome these barriers are also briefly presented.