Mepolizumab improvements in health-related quality of life and disease symptoms in a patient population with very severe chronic rhinosinusitis with nasal polyps: psychometric and efficacy analyses from the SYNAPSE study

Journal of Patient-Reported Outcomes

Research

Robert H. Chan¹  Ana R. Sousa¹  Bhabita Mayer²  Zuzana Diamant³  Wytske Fokkens⁴  Stella E. Lee⁵  Claire Hopkins⁶  Peter Howarth⁷  Andrew Trigg⁸  Maggie Tabberer⁹  Steve Yancey^1,10  Valerie Lund^1,11 

[1] Clinical Sciences, Respiratory, GSK, GSK House, Brentford, Middlesex, UK;Clinical Statistics, GSK, GSK House, Brentford, Middlesex, UK;Department of Microbiology Immunology and Transplantation, KU Leuven, Catholic University of Leuven, Leuven, Belgium;Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, Groningen, The Netherlands;Respiratory Medicine and Allergology, Skane University, Lund, Sweden;Department of Otolaryngology, University of Amsterdam, Amsterdam, The Netherlands;Division of Otolaryngology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA;ENT Department, Guys and St Thomas’s Hospital, King’s College, London, UK;Global Medical Affairs, GSK, Brentford, Middlesex, UK;Patient-Centred Outcomes, Adelphi Values, Bollington, Cheshire, UK;Respiratory Patient Centered Outcomes, Value Evidence and Outcomes GSK, GSK House, Brentford, Middlesex, UK;Respiratory Therapeutic Area Unit, GSK, Research Triangle Park, NC, USA;Royal National Throat, Nose and Ear Hospital, University College London Hospitals, London, UK;

关键词: SNOT-22;    VAS;    Chronic rhinosinusitis with nasal polyps;    Psychometric;    Efficacy;    Quality of life;    Severity;    Mepolizumab;    Patient-reported outcome measures (PROMs);   

DOI  :  10.1186/s41687-023-00543-5

 received in 2022-01-04, accepted in 2023-01-04,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundAlthough the psychometric properties of patient-reported outcome measures (e.g. the 22-item Sino-nasal Outcomes Test [SNOT-22]) in chronic rhinosinusitis with nasal polyps (CRSwNP) have been defined, these definitions have not been extensively studied in patients with very severe CRSwNP, as defined by recurrent disease despite ≥ 1 previous surgery and a current need for further surgery. Therefore, the psychometric properties of the symptoms visual analogue scales (VAS) were evaluated, and meaningful within-patient change thresholds were calculated for VAS and SNOT-22.MethodsSYNAPSE (NCT03085797), a randomized, double-blind, placebo-controlled, 52-week trial, assessed the efficacy and safety of 4-weekly mepolizumab 100 mg subcutaneously added to standard of care in very severe CRSwNP. Enrolled patients (n = 407) completed symptom VAS (six items) daily and SNOT-22 every 4 weeks from baseline until Week 52. Blinded psychometric assessment of individual and composite VAS was performed post hoc, including anchor-based thresholds for meaningful within-patient changes for VAS and SNOT-22, supported by cumulative distribution function and probability density function plots. The effect of mepolizumab versus placebo for 52 weeks on VAS and SNOT-22 scores was then determined using these thresholds using unblinded data.ResultsInternal consistency was acceptable for VAS and SNOT-22 scores (Cronbach’s α-coefficients ≥ 0.70). Test–retest reliability was demonstrated for all symptom VAS (Intra-Class Correlation coefficients > 0.75). Construct validity was acceptable between individual and composite VAS and SNOT-22 total score (r = 0.461–0.598) and between individual symptom VAS and corresponding SNOT-22 items (r = 0.560–0.780), based upon pre-specified ranges. Known-groups validity assessment demonstrated generally acceptable validity based on factors associated with respiratory health, with all VAS responsive to change. Mepolizumab treatment was associated with significantly increased odds of meeting or exceeding meaningful within-patient change thresholds, derived for this very severe cohort using six anchor groups for individual VAS (odds ratio [OR] 2.19–2.68) at Weeks 49–52, and SNOT-22 (OR 1.61–2.96) throughout the study.ConclusionsSymptoms VAS and SNOT-22 had acceptable psychometric properties for use in very severe CRSwNP. Mepolizumab provided meaningful within-patient improvements in symptom severity and health-related quality of life versus placebo, indicating mepolizumab provides substantial clinical benefits in very severe CRSwNP.

【 授权许可】

CC BY   
© The Author(s) 2023

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