[Comment] New hope for neurotrophin targeting in osteoarthritis pain?

New hope for neurotrophin targeting in osteoarthritis pain? Affiliations & Notes Kennedy Institute of Rheumatology, University of Oxford, Oxford OX3 7FY, UK Article Info Publication History: Published March 28, 2026 DOI: 10.1016/S0140-6736(26)00301-6 External LinkAlso available on ScienceDirect External Link Copyright: © 2026 Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies. Linked Articles Download started OkDespite its enormous global burden, osteoarthritis has no licensed disease-modifying treatments, and available analgesics have moderate efficacy and substantial side-effects.1 The success of neutralising antibodies to nerve growth factor (NGF) for osteoarthritis pain in 20102 could arguably have been described as the most important clinical advance in osteoarthritis since surgical joint replacement in the 1960s. Not only did the anti-NGF monoclonal antibody show a level of analgesia which surpassed all licensed osteoarthritis pain medications, but it also led to a greater understanding of the pathophysiology of osteoarthritis pain. However, in 2021 its development was halted when a joint US Food and Drug Administration advisory panel voted against its recommendation for licensing due to safety concerns and insufficient benefit over existing drugs. The European Medicines Agency followed suit. References 1. Vincent, TL ∙ Watt, FE Osteoarthritis Medicine. 2025; 53:834-843 2. Lane, NE ∙ Schnitzer, TJ ∙ Birbara, CA ∙ et al. Tanezumab for the treatment of pain from osteoarthritis of the knee N Engl J Med. 2010; 363:1521-1531 3. Batchelor, V ∙ Perry, TA ∙ Cader, MZ ∙ et al. Peripheral neuronal sensitization and neurovascular remodelling in osteoarthritis pain Nat Rev Rheumatol. 2025; 21:526-545 4. Driscoll, C ∙ Chanalaris, A ∙ Knights, C ∙ et al. Nociceptive sensitizers are regulated in damaged joint tissues, including articular cartilage, when osteoarthritic mice display pain behavior Arthritis Rheumatol. 2016; 68:857-867 5. Ji, Q ∙ Zheng, Y ∙ Zhang, G ∙ et al. Single-cell RNA-seq analysis reveals the progression of human osteoarthritis Ann Rheum Dis. 2019; 78:100-110 6. Conaghan, PG ∙ Katz, N ∙ Bihlet, AR ∙ et al. Efficacy and safety of LEVI-04 in patients with osteoarthritis of the knee: a randomised, double-blind, placebo-controlled, phase 2 trial Lancet. 2026; 407:1237-1248 7. Dakin, P ∙ DiMartino, SJ ∙ Gao, H ∙ et al. The efficacy, tolerability, and joint safety of fasinumab in osteoarthritis pain: a phase IIb/III double-blind, placebo-controlled, randomized clinical trial Arthritis Rheumatol. 2019; 71:1824-1834 8. Tive, L ∙ Bello, AE ∙ Radin, D ∙ et al. Pooled analysis of tanezumab efficacy and safety with subgroup analyses of phase III clinical trials in patients with osteoarthritis pain of the knee or hip J Pain Res. 2019; 12:975-995 9. DiMartino, SJ ∙ Mei, J ∙ Schnitzer, TJ ∙ et al. A phase III study to evaluate the long-term safety and efficacy of fasinumab in patients with pain due to osteoarthritis of the knee or hip Osteoarthr Cartil Open. 2024; 6, 100533 10. Zhang, B ∙ Tian, X ∙ Qu, Z ∙ et al. Relative efficacy and safety of tanezumab for osteoarthritis: a systematic review and meta-analysis of randomized-controlled trials Clin J Pain. 2021; 37:914-924 11. Carrino, JA ∙ McAlindon, TE ∙ Schnitzer, TJ ∙ et al. Characterization of adverse joint outcomes in patients with osteoarthritis treated with subcutaneous tanezumab Osteoarthritis Cartilage. 2023; 31:1612-1626 12. Roemer, FW ∙ Hochberg, MC ∙ Carrino, JA ∙ et al. Role of imaging for eligibility and safety of a-NGF clinical trials Ther Adv Musculoskelet Dis. 2023; 15 1759720X231171768 13. Doherty, M ∙ Jones, A Indomethacin hastens large joint osteoarthritis in humans—how strong is the evidence? J Rheumatol. 1995; 22:2013-2016