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  • Review Article
  • Published:

Emerging pharmaceutical therapies for osteoarthritis

Nature Reviews Rheumatology volume 16, pages 673–688 (2020)Cite this article

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Abstract

The prevalence of osteoarthritis (OA) and the burden associated with the disease are steadily increasing worldwide, representing a major public health challenge for the coming decades. The lack of specific treatments for OA has led to it being recognized as a serious disease that has an unmet medical need. Advances in the understanding of OA pathophysiology have enabled the identification of a variety of potential therapeutic targets involved in the structural progression of OA, some of which are promising and under clinical investigation in randomized controlled trials. Emerging therapies include those targeting matrix-degrading proteases or senescent chondrocytes, promoting cartilage repair or limiting bone remodelling, local low-grade inflammation or Wnt signalling. In addition to these potentially disease-modifying OA drugs (DMOADs), several targets are being explored for the treatment of OA-related pain, such as nerve growth factor inhibitors. The results of these studies are expected to considerably reshape the landscape of OA management over the next few years. This Review describes the pathophysiological processes targeted by emerging therapies for OA, along with relevant clinical data and discussion of the main challenges for the further development of these therapies, to provide context for the latest advances in the field of pharmaceutical therapies for OA.

Key points

  • Osteoarthritis (OA) is a very common and severely debilitating disease with an unmet medical need, and new drugs are needed to alleviate OA symptoms and/or prevent structural progression.

  • Several drugs, such as sprifermin and MIV-711, have been shown to prevent cartilage loss or protect subchondral bone in OA, and thus represent potential disease-modifying OA drugs (DMOADs).

  • The clinical benefits of the positive structural outcomes observed with DMOADs, as well as their long-term safety, remain unclear.

  • Nerve growth factor inhibitors (such as tanezumab and fasinumab) improve pain and function in severe knee or hip OA, but are associated with an increased risk of rapidly progressive OA.

  • Biologic drugs (including IL-1β and TNF inhibitors) and bisphosphonates have yielded disappointing results in OA.

  • The clinical heterogeneity of OA is one of the major challenges for the development of DMOADs, as different phenotypes could require specific therapeutics.

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Fig. 1: Drugs targeting cartilage breakdown or promoting cartilage repair in OA.
Fig. 2: Drugs targeting subchondral bone remodelling in OA.
Fig. 3: Drugs targeting synovial inflammation in OA.
Fig. 4: Drugs targeting pain in OA.

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Authors and Affiliations

  1. Rheumatology Department, Lariboisière Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France

    Augustin Latourte & Pascal Richette

  2. Inserm U1132, UFR de médecine, Université de Paris, Paris, France

    Augustin Latourte & Pascal Richette

  3. Department of Rheumatology Leiden University Medical Center, Leiden, Netherlands

    Margreet Kloppenburg

  4. Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, Netherlands

    Margreet Kloppenburg

Authors
  1. Augustin Latourte
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  2. Margreet Kloppenburg
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  3. Pascal Richette
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A.L. wrote the article. All authors researched data for the article, made a substantial contribution to discussion of content and reviewed or edited the manuscript before submission.

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Correspondence to Augustin Latourte.

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Competing interests

A.L. has received consultancy fees from Pfizer. M.K. has acted as a consultant for Abbvie, Flexion, GlaxoSmithKline, Kiniksa, Levicept, Merck Serono and Pfizer, with fees paid to her institution; she has received royalties from Wolters Kluwer for contributing to Up-to-Date and from Springer Verlag for contributing to “Reumatologie en klinische immunologie”; and she has received grant funding from the Dutch Arthritis Association, European League Against Rheumatism and IMI/APPROACH. P.R. has received consultancy fees from BioIberica, Expanscience, Genévrier, Labrha, Pierre Fabre and Pfizer.

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Nature Reviews Rheumatology thanks C. Ding and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Latourte, A., Kloppenburg, M. & Richette, P. Emerging pharmaceutical therapies for osteoarthritis. Nat Rev Rheumatol 16, 673–688 (2020). https://doi.org/10.1038/s41584-020-00518-6

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