Add-on mepolizumab for chronic rhinosinusitis with nasal polyps: SYNAPSE study

Prof. Martin Wagenmann MD is presenting the data on behalf of all the authors with their permissions. The abstract was previously presented at ERS2020, Eur Respir J. 2020;56(Suppl. 64):4616. Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is an inflammatory disease with recalcitrant symptoms. NP tissue eosinophils lead to recurrence, which often require repeat surgeries. Aims: To assess the efficacy and safety of 4-weekly add-on mepolizumab 100 mg SC in adults with CRSwNP. Methods: SYNAPSE (NCT03085797), a randomised, double-blind, placebo-controlled, multicentre, 52-week study, included patients with severe bilateral NP, treated with intranasal corticosteroids; with a prior NP surgery and eligible for repeat surgery. Co-primary endpoints: changes in total endoscopic NP score (Week 52) and nasal obstruction VAS score (Weeks 49 – 52). Secondary endpoints: time to first NP surgery (key); overall VAS symptom score, Sinonasal Outcome Test-22 score; systemic corticosteroid (SCS) use, composite and loss of smell VAS scores. Safety was assessed. Results: Total endoscopic NP score and nasal obstruction VAS score significantly improved (p < 0.001) with mepolizumab (n = 206) vs. placebo (n = 201). Median change in endoscopic NP score showed a 1-point improvement with mepolizumab (adjusted: − 0.73 [95% CI:-1.11,-0.34]); median change in nasal obstruction VAS score showed a > 3-point improvement (adjusted: − 3.14 [− 4.09,-2.18]). All secondary endpoints significant. Mepolizumab reduced NP surgery by 57% (hazard ratio 0.43 [0.25,0.76]; p = 0.003), improved SNOT-22, VAS (overall, composite, loss of smell) and SCS use. No new safety issues with mepolizumab. Nasopharyngitis was the most common AE (23 – 25%). Conclusions: Mepolizumab improved NP size and sinonasal symptoms and reduced NP surgery and SCS use in adults with severe CRSwNP and may be a treatment option in this population. Publication History Article published online: 30 April 2021 © 2021. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany