title: Brief report: intraarticular sprifermin not only increases cartilage thickness, but also reduces cartilage loss: location-independent post hoc analysis using magnetic resonance imaging.
abstract: 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Anatomy, Paracelsus Medical University Salzburg & Nuremberg, Salzburg, Austria and Chondrometrics GmbH, Ainring, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Eckstein
authors.affiliation: Institute of Anatomy, Paracelsus Medical University Salzburg & Nuremberg, Salzburg, Austria and Chondrometrics GmbH, Ainring, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wirth
authors.affiliation: Boston University School of Medicine and Boston Imaging Core Lab, LLC, Boston, Massachusetts.
authors.forename: Ali
authors.initials: A
authors.lastname: Guermazi
authors.affiliation: Institute of Anatomy, Paracelsus Medical University Salzburg & Nuremberg, Salzburg, Austria and Chondrometrics GmbH, Ainring, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Maschek
authors.affiliation: EMD Serono, Billerica, Massachusetts.
authors.forename: Aida
authors.initials: A
authors.lastname: Aydemir
mesh_terms: D000368:Aged; D002358:Cartilage, Articular / Q000187:drug effects* / Q000473:pathology; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D005346:Fibroblast Growth Factors / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007719:Knee Joint / Q000187:drug effects* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome
chemical_list: C113569:fibroblast growth factor 18; D005346:Fibroblast Growth Factors