title: Intraarticular sprifermin (recombinant human fibroblast growth factor 18) in knee osteoarthritis: a randomized, double-blind, placebo-controlled trial.
abstract: OBJECTIVE
  To evaluate the efficacy and safety of intraarticular sprifermin (recombinant human fibroblast growth factor 18) in the treatment of symptomatic knee osteoarthritis (OA).
  
  
  METHODS
  The study was a randomized, double-blind, placebo-controlled, proof-of-concept trial. Intraarticular sprifermin was evaluated at doses of 10 μg, 30 μg, and 100 μg. The primary efficacy end point was change in central medial femorotibial compartment cartilage thickness at 6 months and 12 months as determined using quantitative magnetic resonance imaging (qMRI). The primary safety end points were nature, incidence, and severity of local and systemic treatment-emergent adverse events (AEs) and acute inflammatory reactions, as well as results of laboratory assessments. Secondary end points included changes in total and compartment femorotibial cartilage thickness and volume as assessed by qMRI, changes in joint space width (JSW) seen on radiographs, and pain scores on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC).
  
  
  RESULTS
  One hundred ninety-two patients were randomized and evaluated for safety, 180 completed the trial, and 168 were evaluated for the primary efficacy end point. We found no statistically significant dose response in change in central medial femorotibial compartment cartilage thickness. Sprifermin was associated with statistically significant, dose-dependent reductions in loss of total and lateral femorotibial cartilage thickness and volume and in JSW narrowing in the lateral femorotibial compartment. All groups had improved WOMAC pain scores, with statistically significantly less improvement at 12 months in patients receiving the 100-μg dose of sprifermin as compared with those receiving placebo. There was no significant difference in serious AEs, treatment-emergent AEs, or acute inflammatory reactions between sprifermin and placebo groups.
  
  
  CONCLUSIONS
  No statistically significant relationship between treatment group and reduction in central medial femorotibial compartment cartilage thickness was observed; however, prespecified structural secondary end points showed statistically significant dose-dependent reductions after sprifermin treatment. Sprifermin was not associated with any local or systemic safety concerns.
authors.affiliation: Lund University, Lund, Sweden; University of Southern Denmark, Odense, Denmark.
authors.forename: L Stefan
authors.initials: LS
authors.lastname: Lohmander
authors.forename: Scarlett
authors.initials: S
authors.lastname: Hellot
authors.forename: Don
authors.initials: D
authors.lastname: Dreher
authors.forename: Eduard F W
authors.initials: EF
authors.lastname: Krantz
authors.forename: Dawie S
authors.initials: DS
authors.lastname: Kruger
authors.forename: Ali
authors.initials: A
authors.lastname: Guermazi
authors.forename: Felix
authors.initials: F
authors.lastname: Eckstein
mesh_terms: D000368:Aged; D002358:Cartilage, Articular / Q000187:drug effects / Q000473:pathology; D004311:Double-Blind Method; D005260:Female; D005346:Fibroblast Growth Factors / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007270:Injections, Intra-Articular; D007719:Knee Joint / Q000187:drug effects / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D010919:Placebos; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D010919:Placebos; D011994:Recombinant Proteins; C113569:fibroblast growth factor 18; D005346:Fibroblast Growth Factors