Brief report: intraarticular sprifermin not only increases cartilage thickness, but also reduces cartilage loss: location-independent post hoc analysis using magnetic resonance imaging.

OBJECTIVE: To determine whether an anabolic drug (sprifermin) is capable of reducing cartilage loss wherever it occurs in a given knee, using a subject-specific, location-independent analysis of cartilage change in patients with knee osteoarthritis (OA). METHODS: Study participants (n = 168; ages ≥40 years, 69% women) had symptomatic femorotibial OA not confined to the medial compartment. Sprifermin (10, 30, or 100 µg) or placebo was injected intraarticularly 3 times over 3 weeks, both after randomization (baseline) and 3 months later. Coronal magnetic resonance images were acquired at baseline and 3, 6, and 12 months after treatment. The femorotibial cartilage of each subject was segmented, and changes in cartilage thickness were computed across 16 subregions. Location-independent post hoc analysis was used to compute summary scores of negative and positive changes in the subregions, summarized as the total cartilage thinning sum score (ThCTnS) and the total cartilage thickening sum score (ThCTkS), capturing change in either direction in each knee. Ordered values of the magnitude of subject-specific subregional changes in thickness were determined. The ThCTnS and ThCTkS in each sprifermin dose group at 12 months of followup were compared with the values in the matched placebo groups, using the Wilcoxon-Mann-Whitney test. RESULTS: The mean ± SD ThCTnS was -591 ± 617 µm (median -360 µm, Q1/Q3 = -820/-200 µm) in patients treated with 100 µg sprifermin (n = 57), and -921 ± 777 µm (median -745 µm, Q1/Q3 = -1,190/-380 µm) in patients given placebo (n = 18). The mean difference in the ThCTnS between the 100-µg sprifermin group and the placebo group was 331 µm (95% confidence interval [95% CI] 24, 685), a difference that was statistically significant (P = 0.03). The mean difference in the ThCTkS in the 100-µg sprifermin group compared with the placebo group was 237 µm (95% CI 34, 440), also a statistically significant difference (P = 0.028). CONCLUSION: Sprifermin not only increases cartilage thickness, but also reduces cartilage loss. Subject-specific, location-independent analysis of both cartilage thinning and thickening represents a sensitive and informative approach for studying the effects of disease-modifying OA drugs.