De Benedetti 2018.

Methods	RCT. Placebo‐controlled, double blind. Parallel design. Duration: 16 weeks.
Participants	Participants with hereditary periodic fevers, including crFMF, hyper‐immunoglobulin D Syndrome (also mevalonate kinase deficiency (HIDS/MKD), and tumor necrosis factor receptor associated periodic syndrome (TRAPS). 1 cohort per disease. crFMF was diagnosed with the Tel‐Hashomer criteria, and fulfil the following criteria: • at least 1 known MEFV exon 10 mutation, • at least 1 fever episode per month despite a standard dose of colchicine (1.5 mg to 3.0 mg/day or equivalent paediatric‐adjusted regimen) or at least 1 fever episode per month with unacceptable side effects to colchicine. 63 participants with crFMF randomized.
Interventions	Intervention: canakinumab 150 mg (or 2 mg/kg for participants weighing ≤ 40 kg) every 4 weeks for 16 weeks. Control: placebo.
Outcomes	Primary outcome measure Proportion of participants who had a complete response, defined as resolution of the baseline flare at day 15 (PGA score of ＜2 plus CRP level of ≤10 mg/L or a reduction by ≥70% from baseline) and no new flare (PGA score of ≥2 and CRP level of ≥30 mg/L) until week 16. Secondary outcome measure Proportion of participants who had a PGA score ＜2, a CRP level ≤10 mg/L, or a SAA level ≤10 mg/L at week 16.
Notes	ClinicalTrials.gov Identifier: NCT02059291. In the subsequent phase up to week 40, participants who had a complete response underwent a second randomization to receive canakinumab or placebo every 8 weeks. Participants who underwent a second randomization and had a subsequent flare and all other participants received open‐label canakinumab.

crFMF: colchicine resistant/intolerant familial Mediterranean fever
 CRP: C‐reactive protein
 PGA: physician's global assessment
 SAA: serum amyloid A