Unbiased Analysis of Knee Cartilage Thickness Change Over Three Years Post-Treatment with Sprifermin vs. Placebo – A Post-Hoc Analysis from the Phase II FORWARD Study

Abstract

ObjectivePost-treatment cartilage morphometry in the FORWARD study was performed without blinding to MRI acquisition order, involving potential reader bias. Here we obtained unbiased estimates of cartilage change post-treatment, reading year (Y)2 and Y5 MRIs with blinding to time point. We studied whether post-treatment cartilage thickness change differed between sprifermin- and placebo-treated knees. MethodsFORWARD was a 5-year randomized control trial in 549 knee osteoarthritis patients. Here, Y2/Y5 images were analyzed with blinding to relative temporal order and treatment group. Cartilage change during Y2→Y5 was obtained in 337 participants: n=57 treated with placebo intra-articular injections every 6 months (q6M); n=69 with 30μg sprifermin every 12 months (q12M), n=67 with 30μg q6M, n=73 with 100μg q12M, and n=71 with 100μg q6M between baseline (BL) and 18M. Total femorotibial joint (TFTJ) cartilage thickness was the primary analytic focus. ResultsTFTJ cartilage thickness change during Y2→Y5 was -26μm (SD64; 95%CI -32,-19) across the cohort; no statistically significant difference (p=0.80) was observed between treatment or placebo arms (one-way ANOVA). All groups lost cartilage, but the treatment-related difference in cartilage thickness in Sprifermin arms relative to placebo at Y2 was maintained until Y5. Annualized cartilage change in placebo participants was -8.2μm (SD21; 95%CI -14,-2.5) during Y2→Y5 vs. -5.4μm (SD27; 95%CI -13,1.8) during BL→Y2; no significant difference was identified (t-test). ConclusionFORWARD is the first study evaluating post-treatment benefits of a potential disease modifying osteoarthritis drug. Cartilage thickness gained with 100μg sprifermin at Y2 is maintained to Y5 and thus appears viable and sustainable.This is a post-hoc analysis of the FORWARD trial: ClinicalTrials.gov Identifier: NCT01919164