title: Can collagen type II sustain a methotrexate-induced therapeutic effect in patients with long-standing rheumatoid arthritis? A double-blind, randomized trial.
abstract: OBJECTIVE
  Based on the results of two recently published, randomized, double-blind and placebo-controlled studies, a possible improvement in rheumatoid arthritis disease activity after oral tolerization with triple helical collagen type II has been suggested. The goal of this study was to go one step further and ask the question whether collagen type II can sustain the therapeutic effect induced by methotrexate, the most widely accepted disease-modifying anti-rheumatic drug in patients with long-standing rheumatoid arthritis.
  
  
  METHODS
  Ninety-two patients with rheumatoid arthritis on stable therapy with methotrexate were enrolled in a 3 month double-blind, randomized and comparative study to examine the efficacy of oral triple helical collagen type II as compared to continuing methotrexate. The dose of methotrexate (or the respective placebo drug) and of concomitant corticosteroids was not changed and intra-articular corticosteroids were not allowed during the 3 months. The primary study endpoint was disease activity as measured by physician and patients.
  
  
  RESULTS
  While patients under ongoing therapy with methotrexate had, as expected, no change in disease activity, almost all parameters of disease activity and outcome in patients under a daily oral dose of 0.5 mg triple helical collagen type II worsened significantly (highly significant difference in swollen joints, between the two groups, P < 0.0001). No significant differences in side-effects between the two groups during the study period could be demonstrated.
  
  
  CONCLUSIONS
  Substitution of methotrexate with daily 0.5 mg of triple helical collagen type II in patients with rheumatoid arthritis leads to a significant increase in disease activity, suggesting that oral collagen type II at the given dose is not capable of sustaining the methotrexate-induced anti-inflammatory effect in patients with long-standing rheumatoid arthritis.
authors.affiliation: Department of Rheumatology and Physical Medicine, University Hospital Zürich, Switzerland.
authors.forename: H J
authors.initials: HJ
authors.lastname: Häuselmann
authors.forename: M
authors.initials: M
authors.lastname: Caravatti
authors.forename: B
authors.initials: B
authors.lastname: Seifert
authors.forename: K
authors.initials: K
authors.lastname: Wang
authors.forename: P
authors.initials: P
authors.lastname: Bruckner
authors.forename: G
authors.initials: G
authors.lastname: Stucki
authors.forename: B A
authors.initials: BA
authors.lastname: Michel
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D003094:Collagen / Q000627:therapeutic use*; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D007596:Joints / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D009061:Mouth Mucosa / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D003094:Collagen; D008727:Methotrexate