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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

2023; Springer Nature; Volume: 7; Issue: 1 Linguagem: Inglês

10.1186/s41687-023-00543-5

2509-8020

Wytske J. Fokkens, Andrew Trigg, Stella E. Lee, Robert Chan, Zuzana Diamant, Claire Hopkins, Peter Howarth, Valerie J. Lund, Bhabita Mayer, Ana R. Sousa, Steve Yancey, Maggie Tabberer, Ledit Ardusso, Miguel Bergna, María De Salvo, Pedro Elías, Gabriel García, Jorge Máspero, Ramón Luévanos Rojas, Pablo Sáez Scherbovsky, Alberto Tolcachier, Luis Wehbe, Anahí Yáñez, Philip G. Bardin, Sara Barnes, Andrew Gillman, Richard J. Harvey, Chady Sader, Narinder Singh, Jaime Del Carpio, Marie-Noëlle Corriveau, Martin Desrosiers, Arif Janjua, Shaun Kilty, Doron D. Sommer, Leigh J. Sowerby, Peter Spafford, Christian Betz, Achim Beule, Adam Chaker, Mandy Cuevas, Moritz Groeger, Ludger Klimek, Heidi Olze, Carolina van Schaik, Martin Wagenmann, Barbara Wollenberg, Yury M. Yarin, Hyung‐Ju Cho, Hun‐Jong Dhong, Changhoon Kim, Seon-Tae Kim, Chae‐Seo Rhee, Soo Whan Kim, Hyo Yeol Kim, Wytske J. Fokkens, Valeriu Bronescu, Corina Mella, Adriana Neagoş, Doinel Radeanu, Catalin Stefan, Anton Edin, Sergey Karpischenko, Fatimat Khanova, Ekaterina Mirzabekyan, A. Yu. Ovchinnikov, Dmitriy Polyakov, Sergey Ryazantsev, В. М. Свистушкин, Galina Tarasova, V. V. Yakusevich, Cecilia Ahlström Emanuelsson, Johan Hellgren, Mattias Jangard, Anders Mårtensson, Karin Toll, Sean Carrie, Stephen R. Durham, Simon Gane, Jonathan Hobson, Claire Hopkins, Naveed Kara, Samuel Leong, N. Massey, Guy Scaddin, Michael B. Armstrong, James Blotter, Matthew Brown, Timothy Courville, Cecelia Damask, Adam S. DeConde, Dale Ehmer, Adil Fatakia, Christine B. Franzese, Joseph K. Han, Thomas S. Higgins, Edward Kerwin, Craig LaForce, Stella E. Lee, Bradley Marple, Jonathan Matz, Chad M. McDuffie, Steven Miller, Jonathan Moss, N. Mumneh, Robert Nathan, Randall A. Ow, Jeffrey Rosenbloom, Rodney J. Schlosser, Heena Shah-Patel, Ronald Shealy, Ayesha Siddiqi, Stacey L. Silvers, Weily Soong, Richard K. Sterling, Neetu Talreja, Martha Tarpay, Luke Webb, H. James Wedner, Simon K. Wright, David M. Yen,

Asthma and respiratory diseases

Abstract Background Although 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. Methods SYNAPSE (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. Results Internal 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. Conclusions Symptoms 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.