Evaluation of the structure-modifying effects of diacerein in hip osteoarthritis - ECHODIAH, a three-year, placebo-controlled trial

Objective. To evaluate the ability of diacerein, an interleukin-1 beta inhi bitor, to slow the progressive decrease in joint space width observed in pa tients 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 Rheuma tology criteria) received diacerein (50 mg twice a day) or placebo. The min imal hip joint space width was measured by a central reader on yearly pelvi c 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 (4 7%) discontinued the study, mainly because of adverse events in the diacere in group (25% versus 12% with placebo) and because of inefficacy in the pla cebo 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 r eceiving 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 stu dy. However, a post hoe covariate analysis that took into account the use o f analgesics and antiinflammatory drugs showed an effect of diacerein on th e Lequesne functional index. Diacerein was well tolerated during the 3-year study. The most frequent adverse events were transient changes in bowel ha bits. Conclusion. This study confirms previous clinical findings indicating that the demonstration of a structure-modifying effect in hip OA is feasible, an d 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 requir es further investigation.