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

Abstract

In 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. Methods Patients 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. Results Thinning 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. Conclusions Sprifermin increases cartilage thickness, and substantially reduces cartilage loss, expanding FORWARD primary results. Trial registration number NCT01919164.