Masitinib, a tyrosine kinase inhibitor, was effective and well tolerated for the treatment of adults with severely symptomatic indolent or smoldering systemic mastocytosis.

• Phase 3, randomised, double-blind, placebo-controlled study compared safety and efficacy of masitinib vs. placebo in severely symptomatic patients who were unresponsive to optimal symptomatic treatments
• Study period: February 19, 2009 and July 15, 2015
• 135 patients; oral masitinib 6mg/kg daily over 24 weeks with possible extension (n=71) and matched placebo (n=64)
• Excluded patients with cutaneous or non-severe systemic mastocytosis after a protocol amendment
• The primary endpoint was cumulative response (≥75% improvement from baseline within Weeks 8-24) in ≥1 severe baseline symptom: pruritus score ≥9, ≥8 flushes/week, Hamilton Rating Scale for Depression ≥19, or Fatigue Impact Scale ≥75

• By Week 24, masitinib was was associated with a cumulative response of 18.7% in the primary endpoint vs. 7.4% for placebo (difference 11.3%, odds ratio 3.6, 95% CI: 1.2-10.8; P=0.0076)
• Most frequent serious adverse events: diarrhea (4% [masitinib] vs. 2% [placebo]), and urticaria (3% vs. 0%)
• At week 16, proportions of patients who achieved an ACR20 response were: 40% for sirukumab 50mg every 4 weeks, 45% for sirukumab 100mg every 2 weeks and 24% for placebo
• Differences compared with placebo: 0.16 (95% CI 0.09–0.23) for sirukumab 50mg and 0.21 (0.14–0.29) for sirukumab 100mg (both p<0.0001)
• Adverse events similar across groups
• No life-threatening toxicities occurred