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

• Published in: Annals of the rheumatic diseases Vol. 79; no. 4; pp. 525 - 528
• Main Authors: Eckstein, Felix, Kraines, Jeffrey L, Aydemir, Aida, Wirth, Wolfgang, Maschek, Susanne, Hochberg, Marc C
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group Ltd and European League Against Rheumatism 01.04.2020; Elsevier Limited; BMJ Publishing Group
• Subjects: Adult; Aged; Aged, 80 and over; Arthritis; Cartilage; Cartilage diseases; Cartilage, Articular - diagnostic imaging; Cartilage, Articular - pathology; Clinical outcomes; Clinical trials; Double-Blind Method; Drug dosages; Female; Fibroblast growth factor 18; Fibroblast Growth Factors - therapeutic use; Fibroblasts; Growth factors; Humans; Injections, Intra-Articular; knee osteoarthritis; Magnetic Resonance Imaging; Male; Middle Aged; MRI; Net losses; Organ Size; Osteoarthritis; Osteoarthritis, Knee - diagnostic imaging; Osteoarthritis, Knee - drug therapy; Osteoarthritis, Knee - pathology; Patients; Population; Thinning; United States > US; Europe; MRI; knee osteoarthritis
• ISSN: 0003-4967; 1468-2060; 1468-2060
• DOI: 10.1136/annrheumdis-2019-216453

ObjectivesIn the phase II FGF-18 Osteoarthritis Randomized Trial with Administration of Repeated Doses (FORWARD) study, sprifermin demonstrated cartilage modification in the total femorotibial joint and in both femorotibial compartments by MRI in patients with knee osteoarthritis. Here, we evaluate whether sprifermin reduces cartilage loss and increases cartilage thickness, independent of location.MethodsPatients were randomised 1:1:1:1:1 to three once-weekly intra-articular injections of 30 µg sprifermin every 6 months (q6mo); 30 µg sprifermin every 12 months (q12mo); 100 µg sprifermin q6mo; 100 µg sprifermin q12mo; or placebo. Post-hoc analysis using thinning/thickening scores and ordered values evaluated femorotibial cartilage thickness change from baseline to 24 months independent of location. Changes were indirectly compared with those of Osteoarthritis Initiative healthy subjects.ResultsThinning scores were significantly lower for sprifermin 100 µg q6mo versus placebo (mean (95% CI) difference: 334 µm (114 to 554)), with a cartilage thinning score similar to healthy subjects. Thickening scores were significantly greater for sprifermin 100 µg q6mo, 100 µg q12mo and 30 µg q6mo versus placebo (mean (95% CI) difference: 425 µm (267 to 584); 450 µm (305 to 594) and 139 µm (19 to 259), respectively) and more than doubled versus healthy subjects.ConclusionsSprifermin increases cartilage thickness, and substantially reduces cartilage loss, expanding FORWARD primary results.Trial registration number NCT01919164.