BACKGROUND Familial Mediterranean fever, mevalonate kinase deficiency (also known
as the hyper-immunoglobulinemia D syndrome), and the tumor necrosis factor receptor-associated
periodic syndrome (TRAPS) are monogenic autoinflammatory diseases characterized by
recurrent fever flares. METHODS We randomly assigned patients with genetically confirmed
colchicine-resistant familial Mediterranean fever, mevalonate kinase deficiency, or
TRAPS at the time of a flare to receive 150 mg of canakinumab subcutaneously or placebo
every 4 weeks. Patients who did not have a resolution of their flare received an add-on
injection of 150 mg of canakinumab. The primary outcome was complete response (resolution
of flare and no flare until week 16). In the subsequent phase up to week 40, patients
who had a complete response underwent a second randomization to receive canakinumab
or placebo every 8 weeks. Patients who underwent a second randomization and had a
subsequent flare and all other patients received open-label canakinumab. RESULTS At
week 16, significantly more patients receiving canakinumab had a complete response
than those receiving placebo: 61% vs. 6% of patients with colchicine-resistant familial
Mediterranean fever (P<0.001), 35% versus 6% of those with mevalonate kinase deficiency
(P = 0.003), and 45% versus 8% of those with TRAPS (P = 0.006). The inclusion of patients
whose dose was increased to 300 mg every 4 weeks yielded a complete response in 71%
of those with colchicine-resistant familial Mediterranean fever, 57% of those with
mevalonate kinase deficiency, and 73% of those with TRAPS. After week 16, an extended
dosing regimen (every 8 weeks) maintained disease control in 46% of patients with
colchicine-resistant familial Mediterranean fever, 23% of those with mevalonate kinase
deficiency, and 53% of those with TRAPS. Among patients who received canakinumab,
the most frequently reported adverse events were infections (173.3, 313.5, and 148.0
per 100 patient-years among patients with colchicine-resistant familial Mediterranean
fever, those with mevalonate kinase deficiency, and those with TRAPS, respectively),
with a few being serious infections (6.6, 13.7, and 0.0 per 100 patient-years). CONCLUSIONS
In this trial, canakinumab was effective in controlling and preventing flares in patients
with colchicine-resistant familial Mediterranean fever, mevalonate kinase deficiency,
and TRAPS.
