Monosodium urate crystal deposition seen in gout stimulates IL-1 beta OR
IL-1_; release. Canakinumab, a long-acting, fully human anti- IL-1 beta OR
IL-1_; monoclonal antibody, effectively neutralizes IL-1 beta OR IL-1_;.
Methods: This was an 8-week, dose-ranging, multi-center, blinded, doubledummy,
active-controlled trial. Patients (aged 18-80 years) with an acute
gout flare, refractory to or contraindicated to NSAlDs and/or colchicine, were
randomized to one dose of canakinumab 10, 25, 50, 90, 150 mg s.c. or
triamcinolone acetonide (TA) 40 mg i.m. Primary variable was assessed as
pain intensity at 72 h post-dose (0-100 mm VAS). Secondary variables
included pain intensity 24 and 48 h post-dose, time to 50% reduction in pain
intensity, time to recurrence of gout flares up to 8 weeks post-dose, and
rescue medication use.
Results: 191/200 enrolled patients (canakinumab, n_143; TA, n_57)
completed the study. Canakinumab showed significant dose-dependent pain
reduction at 72 h. Canakinumab 150 mg showed superior pain relief versus
TA starting from 24 h: estimated mean difference in pain intensity on VAS
was -11.5 (24 h), -18.2 (48 h), and -19.2 (72 h) (all p_0.05). Canakinumab
150 mg provided a rapid onset of pain relief: median time to 50% reduction
in pain was reached at 1 day with canakinumab 150 mg versus 2 days with
TA (p_0.0006). At Week 8, recurrent flares occurred in 1 patient (3.7%) on
canakinumab 150 mg versus 25 (44.6%) patients on TA (relative risk
reduction, 94%; p_0.006). During 7 days post-dose, 6 patients (22.2%) on
canakinumab 150 mg, and 31 patients (55.4%) on TA, took rescue medication.
Time to first rescue medication was significantly longer with canakinumab
150 mg versus TA (hazard ratio, 0.36; p_0.02). Serious adverse
events (canakinumab _lsqb_n_4_rsqb_ and TA _lsqb_n_1_rsqb_) were considered
not treatment-related by investigators and no patient discontinued
due to adverse events.
Conclusions: Canakinumab 150 mg was well-tolerated, provided rapid and
sustained pain relief in patients with acute gout flares, and significantly
reduced the recurrent flare risk by 94% at 8-weeks post-dose compared with
triamcinolone acetonide.