Background: There was a need to ascertain in a clinical trial the comparative efficacy of diacerein, an IL-1 inhibitor, vis-à-vis celecoxib, a COX-2 inhibitor, in relieving knee osteoarthritis (OA) symptoms.
Objectives: The primary outcome of this study was to show that diacerein is non-inferior to celecoxib in terms of pain reduction (WOMAC A pain subscale) after 6 months of treatment in moderate-to-severe symptomatic knee OA patients.
Methods: A randomised double-blind multicentre trial was conducted in four European countries (Spain, Belgium, Austria, Czech Republic) and in Canada evaluating treatment with diacerein versus celecoxib in patients with OA diagnosed according to ACR criteria, with KL grade 2-3 knee OA and moderate-to-severe pain (VAS pain score [0-100 mm] while walking on a flat surface ≥ 40 mm). Eligible patients were randomised to treatment for 6 months with either diacerein 50 mg once daily for the first month and twice daily thereafter, or celecoxib 200 mg once daily. The primary outcome was the change from baseline in WOMAC pain subscale (0-50 scale) after 6 months of treatment. Secondary outcomes included WOMAC function and stiffness, VAS pain, presence of joint swelling/effusion, rescue medication consumption, percentage of OMERACT-OARSI responders, and SF-36. A total of 380 patients were randomised in the study. The primary outcome assessment on the per protocol set (PPS) (n=288) was followed by sensitivity analysis on the ITT population (n=370). Exploratory statistical analysis on other efficacy criteria and safety were performed.
Results: The analysis of the PPS population showed that the adjusted mean change in WOMAC pain was -11.14 (SEM, 0.91) with diacerein (n=140) and -11.82 (0.89) with celecoxib (n=148). Diacerein met the non-inferiority criterion, as the upper bound of the 95% CI is inferior to the pre-specified non-inferiority margin of 5 (inter-group difference 0.67; 95% CI -1.83 to 3.18; p=0.597). The sensitivity analysis using the ITT population was supportive of those results. All other exploratory outcomes demonstrated no difference between the two treatment groups. The OMERACT-OARSI responder rate (PPS) at 6 months was similar in the diacerein (62.1%) and celecoxib (60.1%) groups. The incidence of adverse events related to drug treatment was in general low and balanced between groups. The only exception was a greater incidence of gastrointestinal side effects (diarrhoea) in the diacerein vs. the celecoxib group (10.2% vs. 3.7%, respectively), but accounted for 4.8% of permanent discontinuation in the diacerein group compared to 1.6% in the celecoxib group. In all but one patient, this diarrhoea was considered to be of a mild-to-moderate grade with complete resolution in all cases.
Conclusion: This clinical trial showed that in patients with moderate-to-severe knee OA pain, diacerein has comparable efficacy to celecoxib with respect to reducing pain and stiffness and improving function after 6 months in a clinically relevant manner. The drug also demonstrated a good safety profile with positive benefit to risk ratio.
Disclosure of Interests: : Jean-Pierre Pelletier Shareholder of: Shareholder in ArthroLab Inc., Grant/research support from: Study funded by TRB Chemedica SA, Consultant for: TRB Chemedica SA, Jean-Pierre Raynauld Consultant for: ArthroLab Inc., Patrice Paiement Employee of: ArthroLab Inc., Johanne Martel-Pelletier Shareholder of: ArthroLab Inc., Consultant for: TRB Chemedica SA
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