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

Felix Eckstein, Jeffrey L Kraines, Aida Aydemir, Wolfgang Wirth, Susanne Maschek, Marc C Hochberg, Felix Eckstein, Jeffrey L Kraines, Aida Aydemir, Wolfgang Wirth, Susanne Maschek, Marc C Hochberg

Abstract

Objectives: 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.

Keywords: MRI; knee osteoarthritis.

Conflict of interest statement

Competing interests: FE is CEO of Chondrometrics GmbH and has received consulting fees from Merck KGaA, Samumed LLC, Abbvie, Bioclinica, Kolon TissueGene, Servier, Galapagos, Novartis and Roche. JLK and AA are employees of EMD Serono Research & Development Institute, Inc. (a business of Merck KGaA, Darmstadt, Germany). WW and SM are co-owners and employees of Chondrometrics GmbH, and WW has received consulting fees from Galapagos. MCH has received consulting fees from Bristol Myers Squibb, Eli Lilly, EMD Serono Research & Development Institute, Inc., Flexion Therapeutics, Galapagos, Hofmann LaRoche, IBSA Biotechniq SA, Novartis Pharma AG, Pfizer, Plexxikon, Samumed LLC, Symic Bio, Theralogix LLC, TissueGene, TLC Biopharmaceuticals and Zynerba.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Ratio of thickening:thinning scores by FORWARD treatment group (modified intent-to-treat population) and in the Osteoarthritis Initiative healthy reference cohort over 24 months. q6mo, every 6-month active cycles; q12mo, every 12-month active cycles.
Figure 2
Figure 2
Mean change from baseline (95% CI) in cartilage thickness (μm) over 24 months for (a) 16 OVs and for (b) the 16 subregions in the sprifermin 100 µg q6mo and placebo groups (modified intent-to-treat population). CLF, condyle lateral femur; CMF, condyle medial femur; LT, lateral tibia; MT, medial tibia; OV, ordered value; q6mo, every 6-month active cycle. *Denotes statistically significant treatment effect: t-test p value

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