Background/Purpose:

Canakinumab (CAN), a selective, fully human, anti-IL-1β monoclonal antibody, may be a potential therapeutic option for treating acute gout attacks and delaying new attacks in these patients (pts). Efficacy and safety of canakinumab was previously demonstrated in two 12-week, multicenter, double-blind, double dummy, active controlled trials (β-RELIEVED [N=228]; β-RELIEVED II [N=226]).¹ Health-related quality of life was also measured in these studies, but not all patients completed each questionnaire. Therefore, a composite health outcomes response endpoint was developed to better interpret each patient’s overall response to treatment.

Methods:

This analysis used pooled data from the β-RELIEVED program, which included pts meeting ACR 1977 preliminary criteria for acute GA and contraindicated, intolerant or unresponsive to NSAIDs and/or colchicine.¹ A composite response endpoint representing overall change in gout-related health outcomes, from baseline to 12 weeks, included clinical markers (serum urate and flare activity); patient-reported data from the Gout Impact Scale (GIS) of the Gout Assessment Questionnaire² 2.0 (comprising 6 items related to pain and quality of life); and the SF-36 (Table). Variables represented outcome domains comprising a composite response to GA treatment as recommended by expert rheumatologists.³ Patients were categorized as responders for each variable if they had greater than a minimally important change (per published literature) from baseline. Variable values [1 (responder) or 0 (nonresponder)] were added to create a composite responder endpoint for each patient (Cronbach’s α = 0.76).

Results:

For 8 out of 12 variables measured, the percentage of CAN responders was significantly greater than that for TA (Table, P<0.05). Mean composite response scores were significantly higher for CAN pts vs TA pts (mean [SD]; 4.7 [2.7] vs 3.7 [2.4], P<0.001). Overall, pts receiving CAN also met a higher percentage of response criteria (65%) than pts given TA (49%), P<0.001. Treatment differences remained even after serially removing individual responder variables and domains from the composite endpoint, indicating that the differences between CAN and TA were robust.

Conclusion:

These results demonstrate superior efficacy, across multiple health-outcomes variables comprising clinical markers and patient reported outcomes, of CAN versus TA over 12 weeks in patients contraindicated, intolerant or unresponsive to NSAIDS and/or colchicine.

References:

1.       So A et al., ACR 2011, Chicago, Illinois [Abstract #23697].

2.       Hirsch et al., Journal of Rheumatology 2008; 35(12):2406-2414.

3.       Taylor et al., Journal of Rheumatology 2011; 38(7):1467-1470.

4.       Khanna et al., Rheumatology 2011; 50(7): 1331-1336.

5.       Kosinski, et al., Arthritis & Rheumatism 2000; 43(7):1478-1487.