Mepolizumab Improves Health Related Quality of Life for Patients with Chronic Rhinosinusitis with Nasal Polyps: Data from the SYNAPSE study

Abstract

To report the efficacy of 4-weekly add-on mepolizumab 100 mg SC on health-related quality of life (HRQoL) in adults with Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) . SYNAPSE (NCT03085797), a randomised, double-blind, placebo-controlled, multicentre, 52-week study, enrolled adult patients with highly symptomatic CRSwNP and prior surgery, treated with intranasal corticosteroids. Co-primary endpoints: change from baseline in endoscopic NP score (Week 52) and nasal obstruction visual analogue scale (VAS) score (Weeks 49–52). HRQoL was measured every 4 weeks using the SinoNasal Outcome Test (SNOT-22), assessing symptoms and impact of CRSwNP. Blinded psychometric analysis of SYNAPSE data and prior qualitative research in patients with CRSwNP was conducted to confirm domain structure and meaningful within-patient change thresholds. Psychometric analyses support a six-domain solution: nasal symptoms, ear/facial symptoms, non-nasal symptoms, fatigue, impact on sleep, and emotional impact supporting the validity of a total score. A threshold of -28 points was defined using anchor-based methods and supported by distribution-based methods. Although substantially greater than previously published thresholds, this value is supported by qualitative patient research. LS mean change from baseline total score at week 52 was -29.5 (SE1.62) for mepolizumab and -15.6 (SE 1.65) for placebo, with 54% and 32% responders respectively (post-hoc analyses). Odds ratio of response was 2.66 95% CI (1.75, 4.04) favouring mepolizumab. Change from baseline in all domain scores was approximately twice as large for mepolizumab compared with placebo, with similar magnitude of improvement across all domains. Mepolizumab significantly and meaningfully improves HRQoL in CRSwNP.