PMID- 24740822
OWN - NLM
STAT- MEDLINE
DCOM- 20140909
LR  - 20160511
IS  - 2326-5205 (Electronic)
IS  - 2326-5191 (Linking)
VI  - 66
IP  - 7
DP  - 2014 Jul
TI  - Intraarticular sprifermin (recombinant human fibroblast growth factor 18) in knee 
      osteoarthritis: a randomized, double-blind, placebo-controlled trial.
PG  - 1820-31
LID - 10.1002/art.38614 [doi]
AB  - 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 mug, 30 mug, and 100 mug. 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-mug 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. CONCLUSION: 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.
CI  - Copyright (c) 2014 by the American College of Rheumatology.
FAU - Lohmander, L Stefan
AU  - Lohmander LS
AD  - Lund University, Lund, Sweden; University of Southern Denmark, Odense, Denmark.
FAU - Hellot, Scarlett
AU  - Hellot S
FAU - Dreher, Don
AU  - Dreher D
FAU - Krantz, Eduard F W
AU  - Krantz EF
FAU - Kruger, Dawie S
AU  - Kruger DS
FAU - Guermazi, Ali
AU  - Guermazi A
FAU - Eckstein, Felix
AU  - Eckstein F
LA  - eng
SI  - ChiCTR/NCT01033994
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Arthritis Rheumatol
JT  - Arthritis & rheumatology (Hoboken, N.J.)
JID - 101623795
RN  - 0 (Placebos)
RN  - 0 (Recombinant Proteins)
RN  - 0 (fibroblast growth factor 18)
RN  - 62031-54-3 (Fibroblast Growth Factors)
SB  - IM
CIN - Nat Rev Rheumatol. 2014 Jun;10(6):322. PMID: 24798571
MH  - Aged
MH  - Cartilage, Articular/drug effects/pathology
MH  - Double-Blind Method
MH  - Female
MH  - Fibroblast Growth Factors/*administration & dosage/adverse effects
MH  - Humans
MH  - Injections, Intra-Articular
MH  - Knee Joint/drug effects/pathology
MH  - Magnetic Resonance Imaging
MH  - Male
MH  - Middle Aged
MH  - Osteoarthritis, Knee/*drug therapy/*immunology/pathology
MH  - Placebos
MH  - Recombinant Proteins/administration & dosage/adverse effects
MH  - Treatment Outcome
EDAT- 2014/04/18 06:00
MHDA- 2014/09/10 06:00
CRDT- 2014/04/18 06:00
PHST- 2013/05/10 00:00 [received]
PHST- 2014/02/25 00:00 [accepted]
PHST- 2014/04/18 06:00 [entrez]
PHST- 2014/04/18 06:00 [pubmed]
PHST- 2014/09/10 06:00 [medline]
AID - 10.1002/art.38614 [doi]
PST - ppublish
SO  - Arthritis Rheumatol. 2014 Jul;66(7):1820-31. doi: 10.1002/art.38614.