Disease-modifying treatments for osteoarthritis (DMOADs) of the knee and hip: lessons learned from failures and opportunities for the future

Summary Osteoarthritis (OA) is the biggest unmet medical need among the many musculoskeletal conditions and the most common form of arthritis. It is a major cause of disability and impaired quality of life in the elderly. We review several ambitious but failed attempts to develop joint structure-mod...

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Bibliographic Details
Published in:Osteoarthritis and cartilage 2016-12, Vol.24 (12), p.2013-2021
Main Authors: Karsdal, M.A, Michaelis, M, Ladel, C, Siebuhr, A.S, Bihlet, A.R, Andersen, J.R, Guehring, H, Christiansen, C, Bay-Jensen, A.C, Kraus, V.B
Format: Article
Language:English
Subjects:
Humans
Knee
Knee Joint
Osteoarthritis
Osteoarthritis, Hip
Osteoarthritis, Knee
Phase III
Phenotypes
Quality of Life
Rheumatology
Treatment
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Summary:Summary Osteoarthritis (OA) is the biggest unmet medical need among the many musculoskeletal conditions and the most common form of arthritis. It is a major cause of disability and impaired quality of life in the elderly. We review several ambitious but failed attempts to develop joint structure-modifying treatments for OA. Insights gleaned from these attempts suggest that these failures arose from unrealistic hypotheses, sub-optimal selection of patient populations or drug dose, and/or inadequate sensitivity of the trial endpoints. The long list of failures has prompted a paradigm shift in OA drug development with redirection of attention to: (1) consideration of the benefits of localized vs systemic pharmacological agents, as indicated by the increasing number of intra-articularly administered compounds entering clinical development; (2) recognition of OA as a complex disease with multiple phenotypes, that may each require somewhat different approaches for optimizing treatment; and (3) trial enhancements based on guidance regarding biomarkers provided by regulatory agencies, such as the Food and Drug Administration (FDA), that could be harnessed to help turn failures into successes.
ISSN:1063-4584
1522-9653
DOI:10.1016/j.joca.2016.07.017