Abstract
New treatment options are needed for osteoarthritis (OA) to slow down the structural progression of the disease; current therapies mostly target pain and function with minimal effectiveness. OA results from an imbalance between catabolic and anabolic factors, and biologic agents either target specific catabolic proinflammatory mediators, such as cytokines, nitric oxide synthesis, or affect anabolism more generally. Biologic agents have dramatic effects in other rheumatic inflammatory diseases such as rheumatoid arthritis; they were hoped to have similar effects in the treatment of OA. In this Review, we will discuss the three main types of cytokine blockers used in knee and hand OA, which target β-nerve growth factor (β-NGF), IL-1β or TNF. We will also discuss inhibitors of nitrogen oxide production and the use of growth factors to treat OA. Among the targeted agents, anti-β-NGF therapy has shown promising results, although cases of rapid destructive arthropathy caution against its widespread use. The future of therapies targeting cytokines, nitrogen oxide synthesis and growth factors in OA is questionable, as results from clinical trials have been repeatedly negative. Strategies in OA therapy need to be reconsidered. New molecules emerging from preclinical data should focus on treating the early phase of the disease where damage may be reversible, and treatment should be modified to fit each patient.
Key Points
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Targeted therapy against β-nerve growth factor (β-NGF) in knee osteoarthritis (OA) has resulted in dramatic improvements in symptoms but reports of unexpected, rapid, destructive arthropathies suggest major safety concerns
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Anti-IL-1β therapy using either intra-articular injection or systemic administration failed to demonstrate any clinical improvement in patients with knee OA
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Systemic and subcutaneous injections have been used to deliver anti-TNF therapy in patients with polyarticular hand OA and knee OA, respectively; neither strategy has resulted in structural effects or clinical improvement
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Therapies targeting nitrogen oxide synthesis (administered orally) or local delivery of growth factors in patients with knee OA did not show clinical or structural improvements
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Future strategies should differentiate between those agents aiming to reduce pain, such as anti-β-NGF treatments, and those targeting structural evolution, which have had disappointing results
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Emerging therapies should fit the natural progression of OA, focus on early disease where changes might be reversible, and take into account the location and heterogeneity of the disease
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X. Chevalier researched data for the article and wrote the article. All authors contributed substantially to discussion of content, and reviewing and editing the manuscript before submission.
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Supplementary information
Supplementary Figure 1
MRI of a knee with OA. (PDF 421 kb)
Supplementary Figure 2
MRI showing a reduction in the extent of bone marrow oedema 6 months after repeated subcutaneous adalimumab injections in a patient with knee OA. (PDF 457 kb)
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Chevalier, X., Eymard, F. & Richette, P. Biologic agents in osteoarthritis: hopes and disappointments. Nat Rev Rheumatol 9, 400–410 (2013). https://doi.org/10.1038/nrrheum.2013.44
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DOI: https://doi.org/10.1038/nrrheum.2013.44
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