SUSTAINED CLINICAL BENEFITS IN PATIENTS WITH CHRONIC RHINOSINUSITIS WITH NASAL POLYPS 24 WEEKS POST-MEPOLIZUMAB TREATMENT

Abstract

<h3>Introduction</h3> SYNAPSE, a Phase 3 study in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP), demonstrated significantly reduced disease severity with 52 weeks of 4-weekly mepolizumab 100 mg versus placebo. The durability of clinical improvements following treatment cessation has not been established. <h3>Methods</h3> Mepolizumab-induced effects versus placebo were evaluated for 24 weeks post-treatment. Exploratory endpoints were mean change from baseline (CFB) in: total endoscopic NP score (NPS) at Week 76 and nasal obstruction visual analogue scale (VAS) score at Weeks 73–76, in patients without surgery (analyzed post hoc); 22-item sinonasal outcome test (SNOT-22) total score at Week 76 in the overall follow-up population. <h3>Results</h3> 134 patients (mepolizumab n=69; placebo n=65) entered follow-up; 26 patients with surgery during SYNAPSE were excluded. There was a larger reduction in NPS from baseline to Week 52 with mepolizumab versus placebo (mean [SD] CFB: -1.5 [1.8] vs -0.6 [1.4]), which persisted throughout the follow-up period (Table). For nasal obstruction VAS score, larger improvements from baseline with mepolizumab versus placebo was maintained from Weeks 49–52 (-5.5 [2.9] vs -3.9 [3.0]) to Weeks 73–76 (-4.4 [3.2] vs -3.9 [3.3]). Larger improvements in SNOT-22 total score with mepolizumab versus placebo were maintained throughout follow-up (Week 52: -40.7 [22.4] vs -17.1 [24.7]; Week 76: -28.5 [26.8] vs -16.7 [25.8]). <h3>Conclusions</h3> Post-treatment, patients with severe CRSwNP maintained mepolizumab-induced improvements in NP size and symptoms. These findings suggest that targeted inhibition of interleukin-5 mediated type 2 inflammation offers a durable clinical response in these patients.