Patients with gouty arthritis (GA) are at a higher risk of cardiovascular disease (CVD) than the general population and CVD comorbidities limit treatment options for acute flares. Acute flares are associated with an increase in inflammatory markers such as hsCRP, which is a risk factor for CVD. We report a post-hoc efficacy and safety analysis of canakinumab (a fully human, anti-IL-1β monoclonal antibody) vs triamcinolone acetonide (TA) in GA patients with CVD comorbidities.
In two, 12-week multi-center, double-blind, double-dummy, active controlled studies, patients ≥18−≤85 yrs meeting ACR 1977 preliminary criteria for GA and contraindicated, intolerant or unresponsive to NSAIDs and/or colchicine, with an onset of flares ≤5 days were randomized to receive a single dose CAN 150mg sc or TA 40mg im, and were re-dosed “on demand” on each new flare. Patients completing the core studies were enrolled into 12-week extension studies to further investigate “on demand” use of canakinumab 150 mg sc or TA 40 mg im on new flare. We report a post hoc analysis in CVD population including patients with a history of heart failure, coronary artery disease, cardiac arrhythmia, ischemic heart disease, and cerebrovascular disease and/or at least one CVD risk factor (stable hypertension, diabetes mellitus, hypercholesterolemia) at baseline. Evaluations included number of patients with new flares over 24 weeks; pain intensity in the most affected joint (0-100 mm VAS) at 72h post dose; effect on hsCRP and SAA and safety.
454 GA patients received treatment (β-RELIEVED, N=228; β-RELIEVED-II, N=226), 225 received CAN and 229 received TA. 319 (70.2%) had either a history of CVD and/or at least one CVD risk factor at baseline, 151 (67.1%) received CAN and 168 (73.4%) received TA. Pain intensity was comparable at baseline (mean±SD CAN: 74.4 mm ±12.37 mm; TA: 73.7±12.28 mm). A significantly lower pain score was reported for CAN vs TA at 72h post dose (LS mean: 25.3 mm vs 35.0 mm, Diff: -9.7 mm; 95% CI: -15.2, -4.3, p=0.0005). Incidence of new flares over 24 weeks was significantly lower for CAN vs TA (24.5% vs 46.4%, odds ratio = 0.37, 95% CI 0.23-0.60, p<0.0001). CRP levels were 39% lower in CAN vs TA 72h post dose (ratio=0.61, 95% CI: 0.50, 0.73, p<0.0001) and 52% lower at 7 days (ratio=0.48, 95% CI: 0.39. 0.59, p<0.0001). SAA levels were 59% lower in CAN vs TA 72h post dose (ratio=0.41; 95% CI: 0.32, 0.53, p<0.0001) and 62% lower at 7 days (ratio=0.38; 95% CI: 0.29, 0.49, p<0.0001). Decrease in blood pressure was observed over 24 weeks in CAN vs TA (mean±SD SBP: -5.1±17.26 mmHg vs -3.4±14.81 mmHg, DBP: -1.4±11.51 mmHg vs -0.4±9.61 mmHg). CAN had more AEs and SAEs (102 [67.5%], 12 [7.9%]) vs TA group (86 [51.2%], 5 [3.0%]). angina pectoris, arrhythmia, myocardial ischemia (1 each) was reported in canakinumab group and aortic valve incompetence and cardiac myopathy (1 each) were reported in TA group. None of the SAEs were reported by investigators as related to study drug. Infections were mostly mild to moderate.
Conclusion: CAN provided superior pain relief, reduced the risk of a new flare and lowered the level of inflammatory markers vs TA in GA patients with CVD or CVD risk factors.
Disclosure: N. Schlesinger, Novartis Pharmaceutical Corporation, 2, Novartis Pharmaceutical Corporation, 5, Takeda, 8 ; J. P. Brown, Abbott, Amgen, BMS, Eli Lilly, Merck,, 2, Amgen, Novartis, Eli Lilly, Warner Chilcott,, 5, Amgen, Novartis, Eli Lilly, Warner Chilcott , 8 ; T. Bardin, Novartis, Ipsen, Menarini, Savient, 5 ; T. Kiechle, Novartis Pharma AG, 3, Novartis Pharma AG, 1 ; A. Shpilsky, Novartis Pharmaceutical Corporation, 1, Novartis Pharmaceutical Corporation, 3 ; R. Alten, Novartis Pharmaceutical Corporation, 2 ; A. So, MSD, Novartis, UCB, Pfizer Inc, 5 .