Noninferiority of diacerein to celecoxib demonstrated for knee OA pain
medwireNews: Diacerein has comparable efficacy to celecoxib for pain reduction in patients with moderate-to-severe symptomatic knee osteoarthritis (OA) and is well tolerated, suggest study findings reported in Rheumatology.
Jean-Pierre Pelletier (University of Montréal Hospital Research Centre, Québec, Canada) and co-authors explain that although COX-2 inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs), and analgesics such as acetaminophen “are popular for acute flare-ups of the disease, their use for an extended period could lead to significant adverse events (AEs) such as cardiovascular diseases, renal and liver toxicity.”
They therefore evaluated diacerein, a symptomatic slow-acting drug for OA that “has been successfully used for the treatment of OA symptoms,” and has demonstrated “a positive benefit-to-risk ratio.”
In the phase 3/4 DISSCO trial, individuals with moderate-to-severe knee OA were randomly assigned to receive either diacerein 50 mg once daily for a month and twice daily thereafter or celecoxib 200 mg once daily.
After 182 days, the adjusted absolute mean reduction in the WOMAC pain score from baseline was 11.1 points with diacerein compared with 11.8 points with celecoxib in the per-protocol population comprising 140 and 148 patients, respectively, giving a between-group difference of 0.7 points where the upper limit of the 95% confidence interval was within the prespecified criteria for noninferiority.
The findings for the WOMAC pain scores at day 182 were similar in the intention-to-treat population, which consisted of 183 patients in the diacerein group and 187 in the celecoxib group.
Both treatments also led to rapid and sustained improvements in the WOMAC subscales of stiffness and function and VAS-measured pain, with no significant differences between the groups over time, report Pelletier and team.
Additionally, a comparable proportion of patients in the diacerein and celecoxib treatment arms had a response at day 182 as assessed by the Outcome Measures in Rheumatology Clinical Trials and Osteoarthritis Research Society International (OMERACT-OARSI) criteria, at 55.6% and 53.3%, respectively.
Other outcomes, such as use of rescue medication and reduction in joint swelling and effusion, were also similar between groups, but there was a trend favoring diacerein in the investigators’ global assessment of therapy response at day 182 and a “slightly but significantly higher” investigator-assessed change in the global assessment of disease activity favoring celecoxib.
The researchers stress, however, that these differences were not perceived by patients and therefore are not considered clinically relevant.
With regard to safety, the incidence of treatment-related AEs was higher in the diacerein than celecoxib group (26.3 vs 17.4%), which was primarily attributed to a higher rate of diarrhea (10.2 vs 3.7%).
The team points out, however, that “[t]hese were considered to be generally mild to moderate, and accounted for only a low incidence of permanent discontinuation in the diacerein group.”
“DISSCO therefore confirms the positive benefit–risk ratio of diacerein in knee OA and re-establishes diacerein as a therapeutic option to avoid the use of COX-2 inhibitors in this indication,” Pelletier et al conclude.
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