Research & Innovation
Publications
Unbiased analysis of knee cartilage thickness change over three years after sprifermin vs. placebo treatment - A post-hoc analysis from the phase 2B FORWARD study
PMU Authors
Felix Eckstein, Wolfgang Wirth
All Authors
Felix Eckstein, Susanne Maschek, Wolfgang Wirth, Christoph Ladel, Asger Reinstrup Bihlet, Chris Knight, Kenneth Somberg, Luping Zhao
Journal association
Osteoarthritis and Cartilage Open
Abstract
Objective: Post-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. Methods: FORWARD 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 30 mu g sprifermin every 12 months (q12 M), n = 67 with 30 mu g q6M, n = 73 with 100 mu g q12 M, and n = 71 with 100 mu g q6M between baseline (BL) and 18 M. Total femorotibial joint (TFTJ) cartilage thickness was the primary analytic focus. Results: TFTJ cartilage thickness change during Y2 -> Y5 was -26 mu m (SD64; 95%CI -32,-19) across the cohort; no statistically significant difference (p = 0.80) was observed between Sprifermin treated 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 -8.2 mu m (SD21; 95%CI -14,-2.5) during Y2 -> Y5 vs. -5.4 mu m (SD27; 95%CI -13,1.8) during BL -> Y2; no significant difference was identified (t-test). Conclusion: FORWARD is the first study evaluating post-treatment benefits of a potential disease modifying osteoarthritis drug. Cartilage thickness gained with 100 mu g 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.
Keywords
Magnetic resonance imaging, CARTILAGE MORPHOMETRY, Clinical trial, DMOAD (sprifermin), Post treatment efficacy