Sprifermin Helps Osteoarthritis Patients Regain Cartilage Thickness
OCTOBER 11, 2019
Marc Hochberg, MD
A team, led by Marc C. Hochberg, MD, University of Maryland, conducted a 549-patient dose finding trial to discover whether intra-articular administration of sprifermin structurally modifies cartilage in patients with knee osteoarthritis.
The trial, dubbed FGF-18 Osteoarthritis Randomized Trial with Administration of Repeated Doses (FORWARD), was conducted at 10 sites over the course of 5 years.
Eligible patients were 40-85 years old with symptomatic, radiographic knee osteoarthritis and Kellgren-Lawrence grade 2 or 3.
Participants were randomized into 5 different groups—intra-articular injections of 100 μg of sprifermin administered every 6 months (n = 110) or every 12 months (n = 110), 30 μg of sprifermin every 6 months (n = 111) or every 12 months (n = 110), or placebo every 6 months (n = 108).
Each treatment consisted of weekly injections over 3 weeks.
In the trial, patients were administered either 30 μg or 100 μg of sprifermin or a placebo every 6 or 12 months and measured structurally modified cartilage based on cartilage thickness found through quantitative magnetic resonance imaging.
They found a significant increase after 2 years in total femorotibial cartilage thickness for 100 μg of sprifermin every 6 months (.05 mm) and every 12 months (.04 mm).
“Compared with placebo, intra-articular administration of 100 μg of sprifermin every 6 or 12 months resulted in improvement in femorotibial joint cartilage thickness after 2 years that was statistically significant, but of uncertain clinical importance; the durability of response also was uncertain,” the authors wrote.
The primary end point of the study was a change in total femorotibial joint cartilage thickness, as measured by quantitative magnetic imaging at 2 years. Secondary end points included 2-year changes from baseline in total Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores.
While the minimal clinically important difference (MCID) is unknown for the primary outcome, for total WOMAC score in patients with hip and knee osteoarthritis, the absolute minimal clinically important difference (MCID) is 7 U (95% CI, 4-10 U) and the percentage MCID is 14% (95% CI, 9-18%).
A total of 474 of the 549 participants completed the 2-year follow-up.
Compared with the placebo group, the changes from baseline to 2 years in total femorotibial joint cartilage thickness was .05 mm (95% CI, .03-.07 mm) for 100 μg of sprifermin administered every 6 months and .04 mm (95% CI, .02-.06 mm) for 100 μg of sprifermin every 12 months.
They also found that the total femorotibial joint cartilage thickness was .02 mm (95% CI, −.01-.04 mm) for 30 μg of sprifermin every 6 months and .01 mm (95% CI, −.01-.03 mm) for 30 μg of sprifermin every 12 months.
The investigators did not find a statistically significant difference in mean absolute change from baseline in total WOMAC scores for 100 μg of sprifermin administered every 6 months or every 12 months, or for 30 μg of the drug every 6 months or every 12 months.
The most frequently treatment-emergent adverse event reported in the study was arthralgia (placebo: n = 46 [43.0%]; 100 μg of sprifermin administered every 6 months: n = 45 [41.3%]; 100 μg of sprifermin every 12 months: n = 50 [45.0%]; 30 μg of sprifermin every 6 months: n = 40 [36.0%]; and 30 μg of sprifermin every 12 months: n = 48 [44.0%]).
The study, “Effect of Intra-Articular Sprifermin vs Placebo on Femorotibial Joint Cartilage Thickness in Patients With Osteoarthritis The FORWARD Randomized Clinical Trial,” was published online in JAMA.