The efficacy and safety of diacerein in the treatment of painful osteoarthritis of the knee: a randomized, multicenter, double-blind, placebo-controlled study with primary end points at two months after the end of a three-month treatment period.
OBJECTIVE
To determine whether the efficacy of diacerein persists at 2 months after the end of a 3-month treatment period, compared with placebo, in patients with painful knee osteoarthritis (OA).


METHODS
After a 1-week nonsteroidal antiinflammatory drug washout period, patients received either diacerein or placebo for 3 months, followed by an off-treatment period of 3 months to determine the carryover effects of the drug. Although patients were followed up through month 6, the primary efficacy end point was the percent change from baseline in pain (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC] A) at month 5 (i.e., 2 months after the end of treatment) compared with placebo. The co-primary efficacy end point was the percent change from baseline in the total WOMAC score, also at month 5 versus placebo.


RESULTS
Two hundred three patients were screened, and 168 patients with painful knee OA were randomized. One hundred sixty-five patients were analyzed in an intent-to-treat analysis. At month 5, diacerein showed statistically significant superiority versus placebo as assessed with both the WOMAC A (P < 0.0001) and the total WOMAC (P < 0.0001), demonstrating the carryover effect of the drug. This superiority was already evident from month 2 for pain (P = 0.001) and month 1 for total WOMAC (P = 0.0021). Diacerein was safe and well tolerated. No serious or previously undocumented adverse events were observed during the study.


CONCLUSIONS
This is the first published study of a symptomatic slow-acting OA drug in which the time of assessment of the primary outcome end points was 2 months after the end of a 3-month treatment period. The results show that diacerein is safe and effective for the treatment of knee OA and has a long carryover effect.
Pavelka
Karel
K
Institute of Rheumatology and Charles University Prague, Prague, Czech Republic. pavelka@revma.cz
Trc
Tomás
T
Karpas
Karel
K
Vítek
Petr
P
Sedlácková
Marie
M
Vlasáková
Vera
V
Böhmová
Jana
J
Rovenský
Jozef
J
D000328:Adult; D000368:Aged; D000880:Anthraquinones / Q000009:adverse effects / Q000627:therapeutic use*; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D023381:Endpoint Determination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000188:drug therapy*; D010147:Pain Measurement; D016896:Treatment Outcome
D000880:Anthraquinones; D000893:Anti-Inflammatory Agents; C025292:diacerein