A1344 - Mepolizumab Reduces Systemic Corticosteroid Use in Patients with Chronic Rhinosinusitis with Nasal Polyps
Author Block: G. L. Chupp¹, I. Alobid², N. Lugogo³, H. H. Kariyawasam⁴, A. Bourdin⁵, A. M. Chaker⁶, A. R. Sousa⁷, N. Martin⁸, S. Yang⁹, B. Mayer¹⁰, R. Chan⁷, A. Matucci¹¹; ¹Yale Center for Asthma and Airway Disease, Yale School of Medicine, New Haven, CT, United States, ²1. Department of Otorhinolaryngology; 2. Institut d'Investigacions Biomediques August Pi i Sunyer, 1.&2. Universitat de Barcelona, Barcelona, Spain, ³Department of Medicine, University of Michigan, Ann Arbor, MI, United States, ⁴Royal National Throat, Nose and Ear Hospital, UCLH London, London, United Kingdom, ⁵1. Departement de Pneumologie et Addictologie; 2. PhyMedExp, 1. Hôpital Arnaud de Villeneuve, CHU Montpellier; 2. University of Montpellier, Montpellier, France, ⁶Department of Otolaryngology, Technical University Munich, Munich, Germany, ⁷Clinical Sciences, GSK R&D, Brentford, London, United Kingdom, ⁸1. Global Medical Affairs; 2. Institute for Lung Health, 1. GSK, Brentford; 2. University of Leicester, 1. London; 2. Leicester, United Kingdom, ⁹Value Evidence and Outcomes, GSK, Collegeville, PA, United States, ¹⁰Clinical Statistics, GSK, Brentford, London, United Kingdom, ¹¹Immunoallergology Unit, University of Florence, Florence, Italy.
Rationale: Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by chronic local eosinophilic inflammation, with interleukin-5 playing a key role in pathogenesis. For patients with poor symptom control despite using intranasal corticosteroids (INCS), systemic corticosteroids (SCS) are often prescribed to address the inflammation, systemically. While SCS may temporarily reduce NP size and improve symptoms, their long-term use is associated with adverse effects. Hence, further treatment options are desired; we assessed the effect of mepolizumab on SCS use for NP in patients with CRSwNP during the Phase III SYNAPSE study. Methods: SYNAPSE (NCT03085797), a randomized, double-blind, placebo-controlled, multicenter study, included patients with severe, bilateral NP treated with INCS who were eligible for repeat surgery. Patients received 4-weekly subcutaneous mepolizumab 100 mg or placebo plus standard of care (SoC) for 52 weeks. As part of SoC, courses of SCS were prescribed, as required, to control NP severity. For the purpose of this study, courses of SCS <7 days apart were considered as one course. Here, we report the following endpoints specific to SCS use for NP, up to Week 52: number of SCS courses, time-to-first course of SCS, number of days on SCS therapy, and prednisolone-equivalent oral corticosteroid (OCS) dose (mg/year). Results: Over the study period, 25% (52/206) of patients receiving mepolizumab and 37% (74/201) of patients receiving placebo were treated with ≥1 course of SCS for NP, indicating that patients were 42% less likely to require ≥1 course of SCS for NP with mepolizumab treatment versus placebo (odds ratio [95% CI]: 0.58 [0.36, 0.92], P=0.020). Similarly, the probability of an initial course of SCS for NP was lower with mepolizumab versus placebo (Figure) from Week 12 onwards. For patients with SCS use for NP, a similar mean (SD) number of days on SCS was recorded for mepolizumab (21.9 [45.8] days) and placebo (19.0 [18.5] days). However, across all patients, the mean (SD) total OCS dose was lower with mepolizumab (109 [257] mg/year) versus placebo (181 [364] mg/year) and fewer patients received ≥200 mg/year of OCS with mepolizumab versus placebo (19% [38/205] vs 31% [61/198]).
Conclusions: Patients with CRSwNP treated with mepolizumab were less likely to require SCS to control NP severity than patients in the placebo group. In addition, mepolizumab treatment was associated with lower average total OCS doses than placebo. These findings support the use of mepolizumab to reduce SCS use in patients with CRSwNP. Funding: GSK (ID:205687/NCT03085797)