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Intra-articular sprifermin given to patients with symptomatic and radiographic knee osteoarthritis has been shown to significantly improve total femorotibial joint cartilage thickness after 2 years, but without significant clinical beneftis. Which begs the question, why is there a disconnect between radiographic disease modification (cartilage thickness) and symptomatic improvement?
Sprifermin, recombinant human fibroblast growth factor 18 (rhFGF18) (insulin-like growth factor 1 bone morphogenetic protein 7), is being developed as a potential anabolic disease-modifying agent for osteoarthritis (DMOAD).
The FORWARD trial enrolled 549 participants who were randomized to 30 μg or 100 μg of sprifermin every 6 or 12 months vs placebo.
Spifermin was given four ways - 100 μg of sprifermin every 6 months (n = 110) or every 12 months (n = 110), or 30 μg of sprifermin every 6 months (n = 111) or every 12 months (n = 110), and placebo every 6 months (n = 108). Each treatment consisted of weekly injections over 3 weeks. The primary end point was change in total femorotibial joint cartilage thickness measured by quantitative magnetic resonance imaging at 2 years.
At 2 years, 86.3% completed the 2-year follow-up. Compared with placebo, the changes from baseline to 2 years in total femorotibial joint cartilage thickness was:
- 100 μg every 6 months - 0.05 mm (95% CI, 0.03 to 0.07 mm)
- 100 μg every 12 months - 0.04 mm (95% CI, 0.02 to 0.06 mm)
- 30 μg every 6 months - 0.02 mm (95% CI, −0.01 to 0.04 mm)
- 30 μg every 12 months 0.01 mm (95% CI, −0.01 to 0.03 mm)
Clinically, there were no statistically significant changes from total WOMAC scores when comparing sprifermin vs. PBO.
It is unclear what benefit may ensue from MRI improvements without clinical benefits.