Biological Therapy for Osteoarthritis, Efficacy and Safety: Focus on Monoclonal Antibodies against Nerve Growth Factor and Fibroblast Growth Factor-18

Lina Zaripova; Mishi Pallav; Damira Tazhibaeva; Natalya Kabdualieva; Zhaina Aitbayeva; Gulshakhar Beglarova; Lazzat Yermentayeva; Karlygash Niyazbekova

doi:10.3889/oamjms.2022.10679

Authors

Lina Zaripova Department of Pathological Physiology named after V.G. Korpachev, Astana Medical University, Astana, Kazakhstan https://orcid.org/0000-0001-8728-0225
Mishi Pallav Faculty of General Medicine, Astana Medical University, Astana, Kazakhstan https://orcid.org/0000-0001-8851-1355
Damira Tazhibaeva Department of Pathological Physiology named after V.G. Korpachev, Astana Medical University, Astana, Kazakhstan
Natalya Kabdualieva Department of Pathological Physiology named after V.G. Korpachev, Astana Medical University, Astana, Kazakhstan
Zhaina Aitbayeva Department of Pathological Physiology named after V.G. Korpachev, Astana Medical University, Astana, Kazakhstan https://orcid.org/0000-0001-7970-0429
Gulshakhar Beglarova Department of Pathological Physiology named after V.G. Korpachev, Astana Medical University, Astana, Kazakhstan
Lazzat Yermentayeva Department of Pathological Physiology named after V.G. Korpachev, Astana Medical University, Astana, Kazakhstan https://orcid.org/0000-0002-7757-3769
Karlygash Niyazbekova Department of Pathological Physiology named after V.G. Korpachev, Astana Medical University, Astana, Kazakhstan

DOI:

https://doi.org/10.3889/oamjms.2022.10679

Keywords:

Osteoarthritis, Biological therapy, Monoclonal antibodies, Anti-NGF, FGF-18

Abstract

Osteoarthritis (OA) is the most common chronic progressive musculoskeletal disease, affected cartilage, and surrounded tissues: Subchondral bones, ligaments, and meniscus. Current OA treatment based on non-steroidal anti-inflammatory drugs, acetaminophen (paracetamol), opioids, and intra-articular corticosteroid injections do not prevent the progression of the disease. Understanding of the pathogenesis of OA with continued structural damage accompanied by chronic pain led to appearance of monoclonal antibodies to fibroblast growth factor-18 (FGF)-18 and anti-nerve growth factor (NGF). This review provides an overview of biological therapy with FGF-18 and anti-NGF for OA. Search process was conducted in PubMed and Google Scholar for the following terms: “FGF-18” or “anti-NGF” and “OA,” “monoclonal antibody” and “OA.” Results of the analysis of clinical trials revealed that therapy targeting NGF resulted in significant analgesic effect and functional improvement of joints in OA; however, it was associated with considerable increase in adverse events. The mon\oclonal antibody to FGF-18 demonstrated the structure-modifying effects on cartilage with decrease the cartilage loss and improvement of cartilage thickness. However, further clinical longitudinal studies characterized the risk-benefit are needed to establish safety and efficacy of these medications.

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References

Quicke JG, Conaghan PG, Corp N, Peat G. Osteoarthritis year in review 2021: Epidemiology and amp; therapy. Osteoarthritis Cartilage. 2022;30(2):196-206. https://doi.org/10.1016/j.joca.2021.10.003 PMid:34695571 DOI: https://doi.org/10.1016/j.joca.2021.10.003

Vitaloni M, Botto-van Bemden A, Sciortino R, Carné X, Quintero M, Santos-Moreno P, et al. A patients’ view of OA: The global osteoarthritis patient perception survey (GOAPPS), a pilot study. BMC Musculoskeletal Disord. 2020;21(1):727. https://doi.org/10.1186/s12891-020-03741-0 PMid:33160349 DOI: https://doi.org/10.1186/s12891-020-03741-0

Arden NK, Perry TA, Bannuru RR, Bruyère O, Cooper C, Haugen IK, et al. Non-surgical management of knee osteoarthritis: Comparison of ESCEO and OARSI 2019 guidelines. Nat Rev Rheumatol. 2021;17(1):59-66. https://doi.org/10.1038/s41584-020-00523-9 PMid:33116279 DOI: https://doi.org/10.1038/s41584-020-00523-9

Kolasinski SL, Neogi T, Hochberg MC, Oatis C, Guyatt G, Block J, et al. 2019 American college of rheumatology/arthritis foundation guideline for the management of osteoarthritis of the hand, hip, and knee. Arthritis Care Res (Hoboken). 2020;72(2):149-62. https://doi.org/10.1002/acr.24131 PMid:31908149 DOI: https://doi.org/10.1002/acr.24131

Bally M, Dendukuri N, Rich B, Nadeau L, Helin-Salmivaara A, Garbe E, et al. Risk of acute myocardial infarction with NSAIDs in real world use: Bayesian meta-analysis of individual patient data. BMJ. 2017;357:j1909. https://doi.org/10.1136/bmj.j1909 PMid:28487435 DOI: https://doi.org/10.1136/bmj.j1909

Krebs EE, Gravely A, Nugent S, Jensen AC, DeRonne B, Goldsmith ES, et al. Effect of opioid vs nonopioid medications on pain-related function in patients with chronic back pain or hip or knee osteoarthritis pain: The SPACE randomized clinical trial. JAMA. 2018;319(9):872-82. https://doi.org/10.1001/jama.2018.0899 PMid:29509867 DOI: https://doi.org/10.1001/jama.2018.0899

Jerosch J. Effects of glucosamine and chondroitin sulfate on cartilage metabolism in OA: Outlook on other nutrient partners especially omega-3 fatty acids. Int J Rheumatol. 2011;2011:969012. https://doi.org/10.1155/2011/969012 PMid:21826146 DOI: https://doi.org/10.1155/2011/969012

Kloppenburg M, Kroon FP, Blanco FJ, Doherty M, Dziedzic KS, Greibrokk E, et al. 2018 update of the EULAR recommendations for the management of hand osteoarthritis. Ann Rheum Dis. 2019;78(1):16-24. https://doi.org/10.1136/annrheumdis-2018-213826 PMid:30154087 DOI: https://doi.org/10.1136/annrheumdis-2018-213826

Johnson KJ, Sanchez HN, Schoenbrunner N. Defining response to TNF-inhibitors in rheumatoid arthritis: The negative impact of anti-TNF cycling and the need for a personalized medicine approach to identify primary non-responders. Clin Rheumatol. 2019;38(11):2967-76. https://doi.org/10.1007/s10067-019-04684-1 PMid:31520227 DOI: https://doi.org/10.1007/s10067-019-04684-1

Kloppenburg M, Peterfy C, Haugen IK, Kroon F, Chen S, Wang L, et al. Phase IIa, placebo-controlled, randomised study of lutikizumab, an anti-interleukin-1α and anti-interleukin-1β dual variable domain immunoglobulin, in patients with erosive hand osteoarthritis. Ann Rheum Dis. 2019;78(3):413-20. https://doi.org/10.1136/annrheumdis-2018-213336 DOI: https://doi.org/10.1136/annrheumdis-2018-213336

Fleischmann RM, Bliddal H, Blanco FJ, SchnitzerTJ, Peterfy C, Chen S, et al. A Phase II trial of lutikizumab, an anti-interleukin-1α/β dual variable domain immunoglobulin, in knee osteoarthritis patients with synovitis. Arthritis Rheumatol. 2019;71(7):1056-69. https://doi.org/10.1002/art.40840 PMid:30653843 DOI: https://doi.org/10.1002/art.40840

Aloe L, Tuveri MA, Carcassi U, Levi-Montalcini R. Nerve growth factor in the synovial fluid of patients with chronic arthritis. Arthritis Rheum. 1992;35(3):351-5. https://doi.org/10.1002/art.1780350315 PMid:1536673 DOI: https://doi.org/10.1002/art.1780350315

Dakin P, DiMartino SJ, Gao H, Maloney J, Kivitz AJ, Schnitzer TJ, et al. The efficacy, tolerability, and joint safety of fasinumab in osteoarthritis pain: A Phase IIb/III double-blind, placebocontrolled, randomized clinical trial. Arthritis Rheumatol. 2019;71(11):1824-34. https://doi.org/10.1002/art.41012 PMid:31207169 DOI: https://doi.org/10.1002/art.41012

Brown MT, Murphy FT, Radin DM, Davignon I, Smith MD, West CR. Tanezumab reduces osteoarthritic hip pain: Results of a randomized, double-blind, placebo-controlled Phase III trial. Arthritis Rheum. 2013;65(7):1795-803. https://doi.org/10.1002/art.37950 PMid:23553790 DOI: https://doi.org/10.1002/art.37950

Moore EE, Bendele AM, Thompson DL, Littau A, Waggie KS, Reardon B, et al. Fibroblast growth factor-18 stimulates chondrogenesis and cartilage repair in a rat model of injury-induced osteoarthritis. Osteoarthritis Cartilage. 2005;13(7):623-31. https://doi.org/10.1016/j.joca.2005.03.003 PMid:15896984 DOI: https://doi.org/10.1016/j.joca.2005.03.003

Gigout A, Guehring H, Froemel D, Meurer A, Ladel C, Reker D, et al. Sprifermin (rhFGF18) enables proliferation of chondrocytes producing a hyaline cartilage matrix. Osteoarthritis Cartilage. 2017;25(11):1858-67. https://doi.org/10.1016/j.joca.2017.08.004 PMid:28823647 DOI: https://doi.org/10.1016/j.joca.2017.08.004

Sanga P, Katz N, Polverejan E, Wang S, Kelly KM, Haeussler J, et al. Long-term safety and efficacy of fulranumab in patients with moderate-to-severe osteoarthritis pain: A Phase II randomized, double-blind, placebo-controlled extension study. Arthritis Rheumatol. 2017;69(4):763-73. https://doi.org/10.1002/art.39943 PMid:27748055 DOI: https://doi.org/10.1002/art.39943

Hochberg MC, Tive LA, Abramson SB, Vignon E, Verburg KM, West CR, et al. When is osteonecrosis not osteonecrosis?: Adjudication of reported serious adverse joint events in the tanezumab clinical development program. Arthritis Rheumatol. 2016;68(2):382-91. https://doi.org/10.1002/art.39492 PMid:26554876 DOI: https://doi.org/10.1002/art.39492

Abdiche YN, Malashock DS, Pons J. Probing the binding mechanism and affinity of tanezumab, a recombinant humanized anti-NGF monoclonal antibody, using a repertoire of biosensors. Protein Sci. 2008;17(8):1326-35. https://doi.org/10.1110/ps.035402.108 PMid:18505735 DOI: https://doi.org/10.1110/ps.035402.108

Lane NE, Schnitzer TJ, Birbara CA, Mokhtarani M, Shelton DL, Smith MD, et al. Tanezumab for the treatment of pain from osteoarthritis of the knee. N Engl J Med. 2010;363(16):1521-31. https://doi.org/10.1056/NEJMoa0901510 PMid:20942668 DOI: https://doi.org/10.1056/NEJMoa0901510

Man GS, Mologhianu G. Osteoarthritis pathogenesis--a complex process that involves the entire joint. J Med Life. 2014;7(1):37-41. PMid:24653755

Berenbaum F, Blanco FJ, Guermazi A, Miki K, Yamabe T, Viktrup L, et al. Subcutaneous tanezumab for osteoarthritis of the hip or knee: Efficacy and safety results from a 24-week randomised Phase III study with a 24-week follow-up period. Ann Rheum Dis. 2020;79(6):800-10. https://doi.org/10.1136/ annrheumdis-2019-216296 PMid:32234715 DOI: https://doi.org/10.1136/annrheumdis-2019-216296

Gow JM, Tsuji WH, Williams GJ, Mytych D, Sciberras D, Searle SL, et al. Safety, tolerability, pharmacokinetics, and efficacy of AMG 403, a human anti-nerve growth factor monoclonal antibody, in two Phase I studies with healthy volunteers and knee osteoarthritis subjects. Arthritis Res Ther. 2015;17:282. https://doi.org/10.1186/s13075-015-0797-9 PMid:26449617 DOI: https://doi.org/10.1186/s13075-015-0797-9

Schnitzer TJ, Khan A, Bessette L, Davignon I, Brown MT, Pixton G, et al. Onset and maintenance of efficacy of subcutaneous tanezumab in patients with moderate to severe osteoarthritis of the knee or hip: A 16-week dose-titration study. Semin Arthritis Rheum. 2020;50(3):387-93. https://doi.org/10.1016/j.semarthrit.2020.03.004 PMid:32252976 DOI: https://doi.org/10.1016/j.semarthrit.2020.03.004

Berenbaum F, Langford R, Perrot S, Miki K, Blanco FJ, Yamabe T, et al. Subcutaneous tanezumab for osteoarthritis: Is the early improvement in pain and function meaningful and sustained? Eur J Pain. 2021;25(7):1525-39. https://doi.org/10.1002/ejp.1764 PMid:33728717 DOI: https://doi.org/10.1002/ejp.1764

Nagashima H, Suzuki M, Araki S, Muto C, Investigators T. Preliminary assessment of the safety and efficacy of tanezumab in Japanese patients with moderate to severe osteoarthritis of the knee: A randomized, double-blind, dose-escalation, placebocontrolled study. Osteoarthritis Cartilage. 2011;19(12):1405-12. https://doi.org/10.1016/j.joca.2011.09.006 PMid:22004765 DOI: https://doi.org/10.1016/j.joca.2011.09.006

Schnitzer TJ, Lane NE, Birbara C, Smith MD, Simpson SL, BrownMT. Long-term open-label study of tanezumab for moderate to severe osteoarthritic knee pain. Osteoarthritis Cartilage. 2011;19(6):639-46. https://doi.org/10.1016/j.joca.2011.01.009 PMid:21251985 DOI: https://doi.org/10.1016/j.joca.2011.01.009

Lohmander LS, Hellot S, Dreher D, Krantz EF, Kruger DS, Guermazi A, et al. Intraarticular sprifermin (recombinant human fibroblast growth factor 18) in knee osteoarthritis: A randomized, double-blind, placebo-controlled trial. Arthritis Rheumatol. 2014;66(7):1820-31. https://doi.org/10.1002/art.38614 PMid:24740822 DOI: https://doi.org/10.1002/art.38614

Eckstein F, Kraines JL, Aydemir A, Wirth W, Maschek S, Hochberg MC. Intra-articular sprifermin reduces cartilage loss in addition to increasing cartilage gain independent of location in the femorotibial joint: Post-hoc analysis of a randomised, placebo-controlled Phase II clinical trial. Ann Rheum Dis. 2020;79(4):525-28. https://doi.org/10.1136/annrheumdis-2019-216453 PMid:32098758 DOI: https://doi.org/10.1136/annrheumdis-2019-216453

Hochberg MC, Guermazi A, Guehring H, Aydemir A, Wax S, Fleuranceau-Morel P, et al. Effect of intra-articular sprifermin vs placebo on femorotibial joint cartilage thickness in patients with osteoarthritis: The FORWARD randomized clinical trial. JAMA. 2019;322(14):1360-70. https://doi.org/10.1001/jama.2019.14735 PMid:31593273 DOI: https://doi.org/10.1001/jama.2019.14735

Roemer FW, Aydemir A, Lohmander S, Crema MD, Marra MD, Muurahainen N, et al. Structural effects of sprifermin in knee osteoarthritis: A post-hoc analysis on cartilage and noncartilaginous tissue alterations in a randomized controlled trial. BMC Musculoskelet Disord. 2016;17:267. https://doi.org/10.1186/s12891-016-1128-2 PMid:27393009 DOI: https://doi.org/10.1186/s12891-016-1128-2

Eckstein F, Wirth W, Guermazi A, Maschek S, Aydemir A. Brief report: Intraarticular sprifermin not only increases cartilage thickness, but also reduces cartilage loss: Location-independent post hoc analysis using magnetic resonance imaging. Arthritis Rheumatol. 2015;67(11):2916-22. https://doi.org/10.1002/art.39265 PMid:26138203 DOI: https://doi.org/10.1002/art.39265

Roemer FW, Kraines J, Aydemir A, Wax S, Hochberg MC, Crema MD, et al. Evaluating the structural effects of intra-articular sprifermin on cartilage and non-cartilaginous tissue alterations, based on sqMRI assessment over 2 years. Osteoarthritis Cartilage. 2020;28(9):1229-34. https://doi.org/10.1016/j.joca.2020.05.015 PMid:32619609 DOI: https://doi.org/10.1016/j.joca.2020.05.015

Guehring H, Moreau F, Daelken B, Ladel C, Guenther O, Bihlet AR, et al. The effects of sprifermin on symptoms and structure in a subgroup at risk of progression in the FORWARD knee osteoarthritis trial. Semin Arthritis Rheum. 2021;51(2):450-6. https://doi.org/10.1016/j.semarthrit.2021.03.005 PMid:33752164 DOI: https://doi.org/10.1016/j.semarthrit.2021.03.005

Lane NE, Corr M. Osteoarthritis in 2016: Anti-NGF treatments for pain-two steps forward, one step back? Nat Rev Rheumatol. 2017;13(2):76-8. https://doi.org/10.1038/nrrheum.2016.224 PMid:28119540 DOI: https://doi.org/10.1038/nrrheum.2016.224

Birbara C, Dabezies EJ Jr., Burr AM, Fountaine RJ, Smith MD, Brown MT, et al. Safety and efficacy of subcutaneous tanezumab in patients with knee or hip osteoarthritis. J Pain Res. 2018;11:151-64. https://doi.org/10.2147/JPR.S135257 PMid:29386912 DOI: https://doi.org/10.2147/JPR.S135257

Zhang W, Robertson J, Jones AC, Dieppe PA, Doherty M. The placebo effect and its determinants in osteoarthritis: Metaanalysis of randomised controlled trials. Ann Rheum Dis. 2008;67(12):1716-23. https://doi.org/10.1136/ard.2008.092015 PMid:18541604 DOI: https://doi.org/10.1136/ard.2008.092015