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Brief Report: Intraarticular Sprifermin Not Only Increases Cartilage Thickness, but Also Reduces Cartilage Loss: Location‐Independent Post Hoc Analysis Using Magnetic Resonance Imaging
Author(s) -
Eckstein Felix,
Wirth Wolfgang,
Guermazi Ali,
Maschek Susanne,
Aydemir Aida
Publication year - 2015
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.39265
Subject(s) - cartilage , magnetic resonance imaging , osteoarthritis , post hoc analysis , medicine , placebo , nuclear medicine , mann–whitney u test , knee cartilage , coronal plane , randomization , cartilage damage , surgery , anatomy , radiology , randomized controlled trial , articular cartilage , pathology , alternative medicine
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.