1. Mepolizumab for chronic rhinosinusitis with nasal polyps (SYNAPSE): a randomised, double-blind, placebo-controlled, phase 3 trial
- Author
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Joseph K Han, Claus Bachert, Wytske Fokkens, Martin Desrosiers, Martin Wagenmann, Stella E Lee, Steven G Smith, Neil Martin, Bhabita Mayer, Steven W Yancey, Ana R Sousa, Robert Chan, Claire Hopkins, Cecilia Ahlström Emanuelsson, Ledit Ardusso, Michael Armstrong, Philip Bardin, Sara Barnes, Miguel Bergna, Christian Betz, Achim Beule, James Blotter, Valeriu Bronescu, Matthew Brown, Sean Carrie, Adam Chaker, Hyung-Ju Cho, Marie-Noëlle Corriveau, Timothy Courville, Mandy Cuevas, Cecelia Damask, Adam DeConde, Jaime Del Carpio, María De Salvo, Hun-Jong Dhong, Stephen Durham, Anton Edin, Dale Ehmer Jr, Pedro Elías, Adil Fatakia, Christine Franzese, Simon Gane, Gabriel García, Andrew Gillman, Moritz Groeger, Richard Harvey, Johan Hellgren, Thomas Higgins, Jonathan Hobson, Mattias Jangard, Arif Janjua, Naveed Kara, Sergey Karpischenko, Edward Kerwin, Fatimat Khanova, Shaun Kilty, Chang-Hoon Kim, Seontae Kim, Ludger Klimek, Craig LaForce, Samuel Leong, Bradley Marple, Anders Mårtensson, Jorge Maspero, Neil Massey, Jonathan Matz, Chad McDuffie, Corina Mella, Steven Miller, Ekaterina Mirzabekyan, Jonathan Moss, Nayla Mumneh, Robert Nathan, Adriana Neagos, Heidi Olze, Andrey Ovchinnikov, Randall Ow, Dmitriy Polyakov, Doinel Radeanu, Chae-Seo Rhee, Ramón Rojas, Jeffrey Rosenbloom, Sergei Ryazantsev, Chady Sader, Pablo Saez Scherbovsky, Guy Scadding, Rodney Schlosser, Heena Shah-Patel, Ronald Shealy, Ayesha Siddiqi, Stacey Silvers, Narinder Singh, Doron Sommer, Weily Soong, Leigh Sowerby, Peter Spafford, Catalin Stefan, Richard Sterling, Valeriy Svistushkin, Neetu Talreja, Galina Tarasova, Martha Tarpay, Alberto Tolcachier, Karin Toll Toll, Carolina van Schaik, Luke Webb, H James Wedner, Luis Wehbe, Soo Whan Kim, Barbara Wollenberg, Simon Wright, Vladimir Yakusevich, Anahí Yañez, Yury Yarin, David Yen, Hyo Yeol Kim, Ear, Nose and Throat, and AII - Inflammatory diseases
- Subjects
Adult ,Pulmonary and Respiratory Medicine ,Nasal cavity ,medicine.medical_specialty ,Adolescent ,Visual analogue scale ,Population ,Mometasone furoate ,Antibodies, Monoclonal, Humanized ,Placebo ,03 medical and health sciences ,Nasal Polyps ,0302 clinical medicine ,Double-Blind Method ,Internal medicine ,otorhinolaryngologic diseases ,medicine ,Humans ,Nasal polyps ,030212 general & internal medicine ,education ,education.field_of_study ,business.industry ,medicine.disease ,Treatment Outcome ,medicine.anatomical_structure ,030228 respiratory system ,Synapses ,Nasal administration ,business ,Mepolizumab ,medicine.drug - Abstract
Background: Chronic rhinosinusitis with nasal polyps affects approximately 2–4% of the general population, and long-term use of systemic corticosteroids is associated with adverse effects. The aim of this study was to assess the efficacy and safety of mepolizumab in adults with recurrent, refractory severe bilateral chronic rhinosinusitis with nasal polyps. Methods: SYNAPSE was a randomised, double-blind, placebo-controlled, parallel-group, phase 3 trial done at 93 centres, mainly hospitals, in 11 countries. Eligible patients were aged 18 years or older with recurrent, refractory, severe, bilateral nasal polyp symptoms (nasal obstruction symptom visual analogue scale [VAS] score of >5), were eligible for repeat nasal surgery (overall symptoms VAS score >7 and endoscopic nasal polyps score of ≥5, with a minimum score of 2 in each nasal cavity) despite standard of care treatment, and had to have at least one nasal surgery in the past 10 years. Patients were randomly assigned (1:1), using permuted block design, to receive either 100 mg mepolizumab subcutaneously or placebo once every 4 weeks, in addition to standard of care (mometasone furoate intranasal spray for at least 8 weeks before screening and during the study, saline nasal irrigations, systemic corticosteroids or antibiotics, or both), as required, for 52 weeks. Site staff, the central study team, and patients were masked to study treatment and absolute blood eosinophil counts. The coprimary endpoints were change from baseline in total endoscopic nasal polyp score at week 52 and in mean nasal obstruction VAS score during weeks 49–52, assessed in the intention-to-treat population (ITT). This study is registered with ClinicalTrials.gov, NCT03085797. Findings: From May 25, 2017, to Dec 12, 2018, 854 patients were screened for eligibility. 414 patients were randomly assigned with 407 included in the ITT population; 206 received mepolizumab and 201 received placebo. Total endoscopic nasal polyp score significantly improved at week 52 from baseline with mepolizumab versus placebo (adjusted difference in medians −0·73, 95% CI −1·11 to −0·34; p
- Published
- 2021
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