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

Felix Eckstein; Susanne Maschek; Wolfgang Wirth; Christoph Ladel; Asger Reinstrup Bihlet; Chris Knight; Kenneth Somberg; Luping Zhao

doi:10.1016/j.ocarto.2024.100513

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

Osteoarthr Cartil Open. 2024 Aug 23;6(4):100513. doi: 10.1016/j.ocarto.2024.100513. eCollection 2024 Dec.

Authors

Felix Eckstein^{1

2

3}, Susanne Maschek^{1

2

3}, Wolfgang Wirth^{1

2

3}, Christoph Ladel⁴, Asger Reinstrup Bihlet⁵, Chris Knight⁶, Kenneth Somberg⁶, Luping Zhao⁶

Affiliations

¹ Research Program for Musculoskeletal Imaging, Center for Anatomy & Cell Biology, Paracelsus Medical University (PMU), Salzburg, Austria.
² Ludwig Boltzmann Institute for Arthritis and Rehabilitation (LBIAR), Paracelsus Medical University (PMU), Salzburg, Austria.
³ Chondrometrics GmbH, Freilassing, Germany.
⁴ CHL4special Consulting, Darmstadt, Germany.
⁵ NBCD A/S, Copenhagen, Denmark.
⁶ Formation Bio, New York, NY, United States.

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 μg sprifermin every 12 months (q12 M), n = 67 with 30 μg q6M, n = 73 with 100 μg q12 M, and n = 71 with 100 μg 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 -26μm (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 μm (SD21; 95%CI -14,-2.5) during Y2→Y5 vs. -5.4 μm (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 μg 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: Cartilage morphometry; Clinical trial; DMOAD (sprifermin); Magnetic resonance imaging; Post treatment efficacy.

Associated data

ClinicalTrials.gov/NCT01919164