Background Majority of gouty arthritis (GA) patients (pts) have comorbidities. Chronic kidney disease (CKD) can limit treatment options due to intolerance and contraindications to available therapies. Canakinumab, a fully human monoclonal anti-IL-1β antibody, may present a potential new therapeutic option for treating acute flare pain and delaying new flares in these pts.
Objectives To evaluate the efficacy and safety of canakinumab in GA pts with CKD Stage 3 or worse.
Methods In two 12-week multicenter, double-blind, double-dummy, active controlled studies (β-RELIEVED, N=228; β-RELIEVED II, N=226), pts aged ≥18-≤85 yrs meeting ACR 1977 preliminary criteria for acute GA and contraindicated, intolerant or unresponsive to NSAIDs and/or colchicine received one single dose of canakinumab 150 mg sc or triamcinolone acetonide (TA) 40 mg im and were re-dosed “on demand” on each new flare, followed by a 12-week extension where study completers received canakinumab 150 mg sc or TA 40 mg im only “on demand” upon a new flare. Here, we report a post-hoc efficacy and safety analysis of pooled 24-week data for GA pts with CKD stage 3 or worse (estimated Glomerular Filtration Rate (eGFR) <60mL/min).
Results A total of 114 pts had baseline CKD stage 3 or worse (canakinumab: 65 pts; TA: 49 pts). Over 24 weeks, the probability of new GA flares was lower with canakinumab compared to TA corresponding to a significant relative risk reduction of 54% for time to first new GA flare (hazard ratio 0.46, 95% CI 0.24 to 0.88, p=0.0094[one sided p-value]). Median time to first new flare was >24 weeks with canakinumab vs 19 weeks (133 days) with TA. 73.8% of pts had adverse events (AEs) with canakinumab vs 53.1% with TA. The most frequent AEs (>5%) were hypertension (n=5, 7.7%) with canakinumab and arthralgia (n=3, 6.1%) with TA. Incidence of infections and infestations were higher with canakinumab (27.7%) vs TA (18.4%). Canakinumab showed greater reduction in microalbumin, albumin/creatinine ratio and creatinine levels compared to TA, while blood pressure changes between the groups were minimal (Table). Change from baseline to end of study in the other biochemical parameters (total cholesterol, estimate of the actual GFR [surface area], triglycerides, serum urate) were comparable in both canakinumab and TA groups. A total of 7 (10.8%) pts in canakinumab group experienced SAEs (pneumonia, angina pectoris, gastritis, hyperglycaemia, cerebrovascular accident and intracranial haemorrhage, chronic renal failure, prostatic specific antigen increased, device dislocation). No SAEs were reported with TA. One patient in canakinumab group died due to cerebrovascular accident.
Conclusions CKD limits treatment choices in GA pts. Canakinumab reduced the risk of new flares compared with TA in this population of pts with CKD stage 3 or worse and limited treatment options.
Disclosure of Interest P. Sunkureddi Consultant for: Novartis, Bristol Myers Squibb, UCB, Pfizer., Speakers Bureau: Novartis, Bristol Myers Squibb, UCB, Pfizer., T. Bardin Grant/Research support from: Menarini, Consultant for: Novartis, Ipsen, Menarini, Ardea, Biocryst, R. Alten Grant/Research support from: Novartis, Consultant for: Novartis, Speakers Bureau: Novartis, N. Schlesinger Grant/Research support from: Novartis, Consultant for: Novartis, URL Pharma, Savient, Takeda, Rx Enzyme, Speakers Bureau: Novartis, Takeda, Savient, M. Bloch Grant/Research support from: Novartis, T. Kiechle Shareholder of: Novartis, Employee of: Novartis, G. Krammer Shareholder of: Novartis, Employee of: Novartis, A. Shpilsky Shareholder of: Novartis, Employee of: Novartis, A. So Grant/Research support from: Novartis, Consultant for: Novartis, Ardea, Speakers Bureau: Novartis, Ardea, Menarini