title: Evaluation of the structure-modifying effects of diacerein in hip osteoarthritis: ECHODIAH, a three-year, placebo-controlled trial. Evaluation of the Chondromodulating Effect of Diacerein in OA of the Hip.
abstract: OBJECTIVE
  To evaluate the ability of diacerein, an interleukin-1beta inhibitor, to slow the progressive decrease in joint space width observed in patients with hip osteoarthritis (OA).
  
  
  METHODS
  In this randomized, double-blind, placebo-controlled 3-year study, 507 patients with primary OA of the hip (by the American College of Rheumatology criteria) received diacerein (50 mg twice a day) or placebo. The minimal hip joint space width was measured by a central reader on yearly pelvic radiographs, using a 0.1-mm-graduated magnifying glass.
  
  
  RESULTS
  Baseline characteristics were comparable in the 2 treatment groups (255 patients receiving diacerein, 252 receiving placebo); 238 patients (47%) discontinued the study, mainly because of adverse events in the diacerein group (25% versus 12% with placebo) and because of inefficacy in the placebo group (14% versus 7% with diacerein). The percentage of patients with radiographic progression, defined by a joint space loss of at least 0.5 mm, was significantly lower in patients receiving diacerein than in patients receiving placebo, both in the intent-to-treat analysis and in the completer analysis (50.7% versus 60.4% [P = 0.036] and 47.3% versus 62.3% [P = 0.007], respectively). In those patients who completed 3 years of treatment, the rate of joint space narrowing was significantly lower with diacerein (mean +/- SD 0.18 +/- 0.25 mm/year versus 0.23 +/- 0.23 mm/year with placebo; P = 0.042). Diacerein had no evident effect on the symptoms of OA in this study. However, a post hoc covariate analysis that took into account the use of analgesics and antiinflammatory drugs showed an effect of diacerein on the Lequesne functional index. Diacerein was well tolerated during the 3-year study. The most frequent adverse events were transient changes in bowel habits.
  
  
  CONCLUSIONS
  This study confirms previous clinical findings indicating that the demonstration of a structure-modifying effect in hip OA is feasible, and shows, for the first time, that treatment with diacerein for 3 years has a significant structure-modifying effect as compared with placebo, coupled with a good safety profile. The clinical relevance of these findings requires further investigation.
authors.affiliation: Université René Descartes and Hôpital Cochin, Service de Rhumatologie B, Paris, France. maxime.dougados@cch.ap-hop-paris.fr
authors.forename: M
authors.initials: M
authors.lastname: Dougados
authors.forename: M
authors.initials: M
authors.lastname: Nguyen
authors.forename: L
authors.initials: L
authors.lastname: Berdah
authors.forename: B
authors.initials: B
authors.lastname: Maziéres
authors.forename: E
authors.initials: E
authors.lastname: Vignon
authors.forename: M
authors.initials: M
authors.lastname: Lequesne
mesh_terms: D000880:Anthraquinones / Q000627:therapeutic use*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D004066:Digestive System Diseases / Q000139:chemically induced / Q000503:physiopathology; D004311:Double-Blind Method; D005260:Female; D006621:Hip Joint / Q000000981:diagnostic imaging / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D015207:Osteoarthritis, Hip / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology; D010147:Pain Measurement; D011859:Radiography; D012720:Severity of Illness Index; D012871:Skin Diseases / Q000139:chemically induced / Q000503:physiopathology; D016896:Treatment Outcome; D014570:Urologic Diseases / Q000139:chemically induced / Q000503:physiopathology
chemical_list: D000880:Anthraquinones; D000894:Anti-Inflammatory Agents, Non-Steroidal; C025292:diacerein