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The Development of Disease-Modifying Therapies for Osteoarthritis (DMOADs): The Evidence to Date
Win Min Oo1,2, Christopher Little3, Vicky Duong1
1Rheumatology Department, Royal North Shore Hospital, and Institute of Bone and Joint Research, Kolling Institute, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.
Abstract:
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.
Insights
Developing disease-modifying osteoarthritis drugs (DMOADs) is crucial for managing osteoarthritis. This review explores OA endotypes, targeted drug trials, and strategies to overcome clinical trial failures for effective osteoarthritis treatment.
Area of Science:
- * Rheumatology and Orthopedics
- * Pharmacology and Drug Discovery
- * Biomedical Engineering
Background:
- * Osteoarthritis (OA) is a complex, heterogeneous joint disease impacting multiple tissues.
- * Currently, no approved disease-modifying osteoarthritis drugs (DMOADs) exist, highlighting a critical unmet medical need.
- * Existing OA management focuses on symptom relief rather than disease modification.
Purpose of the Study:
- * To review the rationale for developing DMOADs in osteoarthritis management.
- * To classify OA clinical phenotypes and molecular endotypes for targeted drug discovery.
- * To summarize the efficacy and safety of investigational drugs in clinical trials targeting distinct OA endotypes.
Main Methods:
- * Comprehensive literature review of preclinical and clinical OA research.
- * Analysis of OA endotype classifications relevant to drug development.
- * Synthesis of data from Phase 2 and 3 clinical trials of targeted OA therapies.
Main Results:
- * Identification of distinct OA endotypes (cartilage-driven, bone-driven, inflammation-driven) crucial for targeted therapy.
- * Summary of the efficacy and safety profiles of various DMOAD candidates in clinical development.
- * Analysis of common reasons for clinical trial failures in OA drug development.
Conclusions:
- * Targeted drug discovery based on OA endotypes offers a promising avenue for developing effective DMOADs.
- * Overcoming barriers in clinical trial design and execution is essential for advancing OA therapeutics.
- * Future research should focus on precision medicine approaches for osteoarthritis treatment.
