Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Jul 6:15:2921-2945.
doi: 10.2147/DDDT.S295224. eCollection 2021.

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

Win Min Oo  1   2 , Christopher Little  3 , Vicky Duong  1 , David J Hunter  1
Affiliations
Review

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

Win Min Oo et al. Drug Des Devel Ther. .

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.

Keywords: DMOADs; disease-modifying drugs; endotype; intra-articular therapy; osteoarthritis; phenotype.

PubMed Disclaimer

Conflict of interest statement

DJH provides consulting advice on scientific advisory boards for Pfizer, Lilly, TLCBio, Novartis, Tissuegene, Biobone. CL has provided consulting advice for Merck Serono and Galapagos Pharmaceuticals, and receives research funding from numerous pharmaceutical companies (Fidia Farmaceutici, Inter-K Peptide Therapeutics Ltd, Taisho Pharmaceutical Co. Ltd, Concentric Analgesics Inc, Cynata Therapeutics, CEVA Animal Health, Regeneus) through specific services/testing contract research agreements between and managed by The University of Sydney or the NSLHD. The authors report no other conflicts of interest in this work.

Figures

Figure 1
Figure 1
Active drugs related to the three main molecular or mechanistic OA endotypes (phase 2 and 3).
Figure 2
Figure 2
Reasons for DMOAD trial failures.
See this image and copyright information in PMC

References

    1. Hawker GA. Osteoarthritis is a serious disease. Clin Exp Rheumatol. 2019;37 Suppl 120(5):3–6. - PubMed
    1. OARSI TP-cCfOPo. OARSI White Paper- OA as a Serious Disease; 2016.
    1. Safiri S, Kolahi AA, Smith E, et al. Global, regional and national burden of osteoarthritis 1990–2017: a systematic analysis of the Global Burden of Disease Study 2017. Ann Rheum Dis. 2020;79(6):819–828. doi:10.1136/annrheumdis-2019-216515 - DOI - PubMed
    1. Neogi T. The epidemiology and impact of pain in osteoarthritis. Osteoarthritis Cartilage. 2013;21(9):1145–1153. doi:10.1016/j.joca.2013.03.018 - DOI - PMC - PubMed
    1. Murphy L, Schwartz TA, Helmick CG, et al. Lifetime risk of symptomatic knee osteoarthritis. Arthritis Rheum. 2008;59(9):1207–1213. doi:10.1002/art.24021 - DOI - PMC - PubMed

Substances