Is Sprifermin Beneficial for Knee OA Patients?

A new study found that sprifermin may improve total femorotibial joint cartilage thickness in patients with symptomatic radiographic osteoarthritis (OA) of the knee compared to placebo, although the clinical significance is not clear.

The study, published in JAMA, reported the findings of FORWARD (FGF-18 Osteoarthritis Randomized Trial with Administration of Repeated Doses). The randomized clinical trial spanned five years and 10 sites. FORWARD included patients aged 40 to 85 years with symptomatic, radiographic knee OA and Kellgren-Lawrence grade 2 or 3. Patients were randomly assigned to one of the following five cohorts: intra-articular injections of 100 μg of sprifermin administered every six (n = 110) or 12 (n = 110) months, 30 μg of sprifermin every six (n = 111) or 12 (n = 110) months, or placebo every six months (n = 108). Patients received weekly injections over three weeks. The main outcome measure was total two-year femorotibial joint cartilage thickness change, which was measured by MRI. Secondary outcomes included total two-year change in total Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores. The absolute minimal clinically important difference (MCID) for patients with hip and knee OA is 7 U, and the percentage MCID is 14%.

Of 549 eligible patients (median age, 65 years; 69% were female), 474 completed two-year follow-up. Two-year changes in total femorotibial joint cartilage thickness compared to placebo were 0.05 mm (95% CI, 0.03 to 0.07 mm) for 100 μg of sprifermin administered every six months, 0.04 mm (95% CI, 0.02 to 0.06 mm) for 100 μg of sprifermin every 12 months, 0.02 mm (95% CI, −0.01 to 0.04 mm) for 30 μg of sprifermin every six months, and 0.01 mm (95% CI, −0.01 to 0.03 mm) for 30 μg of sprifermin every 12 months. Mean absolute changes in total WOMAC scores, compared to placebo, did not significantly differ in the 100 μg of sprifermin administered every six or 12 months or 30 μg of sprifermin every six or 12 months groups. The most common adverse event related to treatment was arthralgia (placebo: n = 46 [43.0%], 100 μg of sprifermin administered every six months: n = 45 [41.3%], 100 μg of sprifermin every 12 months: n = 50 [45.0%], 30 μg of sprifermin every six months: n = 40 [36.0%], and 30 μg of sprifermin every 12 months: n = 48 [44.0%]).

The authors wrote in sum, “Among participants with symptomatic radiographic knee osteoarthritis, the intra-articular administration of 100 μg of sprifermin every 6 or 12 months vs placebo resulted in an improvement in total femorotibial joint cartilage thickness after 2 years that was statistically significant, but of uncertain clinical importance; there was no significant difference for 30 μg of sprifermin every 6 or 12 months vs placebo. Durability of response also was uncertain.”