Background: The SYNAPSE study (NCT03085797) demonstrated that mepolizumab decreased nasal polyp (NP) size and nasal obstruction in patients with chronic rhinosinusitis with NP (CRSwNP).
Methods: SYNAPSE, a randomized, double-blind study, included patients with recurrent, refractory, severe CRSwNP, eligible for repeated surgery despite receiving standard of care (SoC). Patients received 4-weekly mepolizumab 100 mg or placebo subcutaneously plus SoC for 52 weeks. This post hoc analysis further characterized treatment responses and association with patient characteristics. The proportion of patients meeting any and each of five response criteria indicating improvement in disease-specific quality of life, NP size, nasal obstruction, loss of smell, and overall symptoms at Weeks 24 and 52, were assessed in subgroups: 1) no surgery; 2) neither surgery nor systemic corticosteroids (SCS).
Results: Of 407 patients in the intention-to-treat population, 381 and 343 patients had no sinus surgery by Weeks 24 and 52, respectively. More mepolizumab- versus placebo-treated patients without surgery by Weeks 24 and 52 met each response criteria. Of the mepolizumab-treated patients without surgery by Week 24, 109 (55%) responded across >=3 criteria, increasing to 126 (67%) by Week 52. Similar response trends were seen for patients with neither surgery nor SCS by Weeks 24 and 52. At either timepoint, there were no major differences in baseline characteristics between mepolizumab-treated full- (5/5 categories) and non-responders (0/5 categories).
Conclusions: Most patients who completed SYNAPSE required neither surgery nor SCS use and in addition achieved a progressive and sustained clinical response to mepolizumab underscoring the therapeutic benefits of mepolizumab in severe CRSwNP.