Background: Masitinib is an oral tyrosine kinase inhibitor that selectively targets mast cell activity and platelet-derived growth factor receptor (PDGFR) signaling, both of which are implicated in various mechanisms of asthma pathogenesis. Objective: Assessment of masitinib as an add-on to standard maintenance therapy as compared with placebo in the treatment of oral corticosteroid-dependent severe asthma. Methods: We conducted a randomized (2:1), placebo-controlled study of masitinib (6 mg/kg/d) in adults with severe asthma uncontrolled by high dose inhaled corticosteroids and long-acting beta-adrenoreceptor agonists plus oral corticosteroids (OCS) (≥ 7.5 mg/d). No minimum baseline blood eosinophil count was specified. Following a protocol amendment, the primary endpoint was reduction of annualized severe asthma exacerbation rate adjusted for the overall time on treatment (SAER). Subgroup analysis according to yearly cumulative OCS intake was also performed, a higher OCS dose indicating more severe asthma that is harder to control. Results: Following an average exposure of approximately 13 months, masitinib (n = 240) reduced the SAER by 35% relative to placebo (n = 115) (rate ratio (RR) 0.65 (95% CI [0.47– 0.90]; P = 0.010)). For patients with eosinophil ≥ 150 cell/μL, masitinib (n = 181) reduced SAER by 38% relative to placebo (n = 87); RR 0.62 (95% CI [0.42– 0.91]; P = 0.016). Benefit of masitinib was shown to increase in the most severely affected patients (OCS intake of > 1000 mg/year), with a significant (P < 0.01) reduction in SAER of 50%– 70%. Safety was consistent with the known masitinib profile. Conclusion: Orally administered masitinib reduces the risk of asthma exacerbations in severe asthma patients, with an acceptable safety profile. Masitinib may potentially provide a new treatment option for oral corticosteroid-dependent severe asthma.

Tobacco use will become the world's foremost cause of premature death and disability within 20 years unless current trends are reversed. Many opportunities to reduce this epidemic are missed in primary care. This Discussion paper from the International Primary Care Respiratory Group (IPCRG) — which reflects the IPCRG's understanding of primary care practitioners' needs — summarises a new approach based on strong evidence for effective interventions. All primary care health professionals can increase smoking cessation rates among their patients, even when time and resources are limited. Medical and non-medical staff can support patients who choose to quit by providing information, referral to telephone counselling services, and behavioural counselling using motivational interviewing techniques, where resources permit. Drug therapy to manage nicotine dependence can significantly improve patients' chances of quitting successfully, and is recommended for people who smoke 10 or more cigarettes per day. All interventions should be tailored to the individual's circumstances and attitudes.