title: Effect of chondroitin sulfate on soluble biomarkers of osteoarthritis: a method to analyze and interpret the results from an open-label trial in unilateral knee osteoarthritis patients.
abstract: The aim of this study was to investigate the effects of chondroitin sulfate (CS) on the serum levels of Coll2-1 in patients with knee OA.
  
  
  
  Seventy two patients with unilateral symptomatic knee OA were involved in a post-authorization open-label study evaluating CS (800 mg/day). The primary outcome was the % relative change in serum Coll2-1 (sColl2-1). The secondary outcomes were the evaluation of pain (VAS) and function (Lequesne's Index). Responders and non-responders were classified according to OMERACT-OARSI recommendations. Finally, an original cut-off method was applied to categorize patients and interpret individual variations in serum levels of Coll2-1.
  
  
  
  Patients showed no difference in the sColl2-1 levels at baseline. When considering responders and non-responders from the ITT population, a significant difference was found for Coll2-1 at 3 months (p = 0.030) and 6 months (p = 0.038). A decrease in pain (VAS) and an improvement in function (LI) were recorded throughout the visits (p < 0.01). Considering an intra-batch cut-off of 21 %, CS decreased Coll2-1 serum levels between baseline and 1-month visit compared to the value of Coll2-1 before treatment (screening visit) which can be interpreted as a drastic reduction of the proportion of patients with an increase of Coll2-1 over 21 % (reduction from 13 to 3 %). It also consisted in a more important proportion of patients with a decrease in Coll2-1 (from 5 to 10 %).
  
  
  
  This study proposes a new approach for the analysis and the interpretation of the individual variation in biomarker levels and introduces the notion of metabolic responders.
  
  
  
  ID ISRCTN63795830 . The trial was retrospectively registered on 2 October, 2015.
authors.affiliation: Poal Institute of Rheumatology, Barcelona, Spain.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Möller
authors.affiliation: Artialis SA, GIGA Tower, CHU Sart-Tilman, 4000, Liège, Belgium.
authors.forename: Myriam
authors.initials: M
authors.lastname: Gharbi
authors.affiliation: Clinical R&D Area, Bioiberica S.A., Barcelona, Spain.
authors.forename: Helena
authors.initials: H
authors.lastname: Martinez Serrano
authors.affiliation: Clinical R&D Area, Bioiberica S.A., Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Herrero Barbero
authors.affiliation: Clinical R&D Area, Bioiberica S.A., Barcelona, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Verges Milano
authors.affiliation: Bone and Cartilage Research Unit, Arthropôle Liège, Institute of Pathology, University of Liège, level +5, CHU Sart-Tilman, 4000, Liège, Belgium. yhenrotin@ulg.ac.be.
authors.forename: Yves
authors.initials: Y
authors.lastname: Henrotin
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002809:Chondroitin Sulfates / Q000008:administration & dosage / Q000627:therapeutic use*; D024043:Collagen Type II / Q000097:blood*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000097:blood* / Q000188:drug therapy*; D059408:Pain Management / Q000379:methods*; D010147:Pain Measurement; D010446:Peptide Fragments / Q000097:blood*; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D024043:Collagen Type II; D010446:Peptide Fragments; C510280:collagen type II (108-116); D002809:Chondroitin Sulfates
keywords: Biomarkers; Cartilage metabolism; Chondroitin sulfate; Osteoarthritis; Pain