Search

Background: In the 52-week Phase III SYNAPSE study, mepolizumab given every 4 weeks (100 mg subcutaneously) reduced nasal polyp (NP) size, improved symptoms and quality of life (QoL), and reduced corticosteroid use and number of sinus surgeries in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP), versus placebo. Because the durability of mepolizumab's efficacy after discontinuation is poorly understood in CRSwNP, the efficacy of mepolizumab after discontinuation was analyzed in severe CRSwNP, over a 24-week follow-up., Methods: Changes from SYNAPSE baseline to end of treatment (week 52) and end of follow-up (week 76) were assessed for total endoscopic NP score, nasal obstruction and overall symptoms visual analog scale scores, and 22-item Sino-Nasal Outcome Test score. Time to first sinus surgery, time to first corticosteroid use, and geometric mean blood eosinophil counts (BECs) were also assessed., Results: Among 134 follow-up patients, clinical improvements observed with mepolizumab versus placebo were partially evident 24 weeks after discontinuation despite BEC returning to baseline. The mean (95% confidence interval [CI]) change from baseline in NP score (week 52: -1.3 [1.8 to -0.9] vs. -0.3 [-0.6 to 0.1]; week 76: -1.2 [-1.6 to -0.7] vs. -0.1 [-0.5 to 0.3]) and the proportion of patients having sinus surgery (week 52: 4% vs. 25%; week 76: 9% vs. 31%) remained substantially improved with mepolizumab versus placebo. Mepolizumab-associated improvements in overall symptoms, quality of life, and corticosteroid use versus placebo were partially sustained at week 76., Conclusion: Fifty-two weeks of mepolizumab treatment is associated with sustained clinical benefits up to 24 weeks after discontinuation in patients with severe CRSwNP, which should be considered by physicians when making treatment decisions., (© 2023 The Authors. International Forum of Allergy & Rhinology published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngic Allergy and American Rhinologic Society.)

Asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) or without (CRSsNP) are chronic respiratory diseases. These two disorders often co-exist based on common anatomical, immunological, histopathological, and pathophysiological basis. Usually, asthma with comorbid CRSwNP is driven by type 2 (T2) inflammation which predisposes to more severe, often intractable, disease. In the past two decades, innovative technologies and detection techniques in combination with newly introduced targeted therapies helped shape our understanding of the immunological pathways underlying inflammatory airway diseases and to further identify several distinct clinical and inflammatory subsets to enhance the development of more effective personalized treatments. Presently, a number of targeted biologics has shown clinical efficacy in patients with refractory T2 airway inflammation, including anti-IgE (omalizumab), anti-IL-5 (mepolizumab, reslizumab)/anti-IL5R (benralizumab), anti-IL-4R-α (anti-IL-4/IL-13, dupilumab), and anti-TSLP (tezepelumab). In non-type-2 endotypes, no targeted biologics have consistently shown clinical efficacy so far. Presently, multiple therapeutical targets are being explored including cytokines, membrane molecules and intracellular signalling pathways to further expand current treatment options for severe asthma with and without comorbid CRSwNP. In this review, we discuss existing biologics, those under development and share some views on new horizons., (© 2023 The Author(s).)

Background: Real-world evidence (RWE) is a valuable instrument to better understand the patient journey and effectiveness of therapies. RWE on the prevalence of uncontrolled chronic rhinosinusitis (CRS) and CRS natural course of disease across Europe is scarce. In addition, there is limited RWE that enables comparison of the effectiveness of marketed therapies including topical or systemic corticosteroids, sinus surgery, or biologics., Objective: To establish an international CHRonic rhINOSinusitis Outcome Registry (CHRINOSOR) based on real-world data collection enabled by mobile health technology., Methodology: A digital platform, Galenus Health, supporting patients and physicians in the management of chronic respiratory diseases, is used to collect data on patient profile, disease history, patient outcomes, and a set of relevant clinical outcomes. Adult patients with a diagnosis of CRS are eligible for inclusion., Results: A collaborative scientific network of 17 university ear-nose-throat (ENT) clinics from 10 European countries has been established with the aim to collect real-world data in a longitudinal and standardized manner. The Galenus Health digital platform is currently being implemented in these ENT clinics taking into account legal, privacy, and data security aspects. Up to 300 patients have already been included., Conclusions: CHRINOSOR is a collaborative effort that aims at improving our understanding of CRS, its comorbidities, and the effectiveness of its treatments. Ultimately, these insights will guide us as scientific community to develop future care pathways informed by RWE., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

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., (© 2023. The Author(s).)

Following the European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) treatment algorithm for chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP), patients suffering from severe uncontrolled CRSwNP are recommended to receive oral corticosteroids, (revision) sinus surgery, systemic biologicals and/or aspirin treatment after desensitization (ATAD). Given the major differences in indications, outcomes, practical considerations, risks and costs of these key pillars of treatment, there is a growing need to define criteria for each treatment option and list the clinically relevant and major considerations for them. This EUFOREA document therefore provides an expert panel overview of the expected outcomes, specific considerations and (contra)indications of the five major treatment arms of severe uncontrolled CRSwNP: oral corticosteroids, primary and revision sinus surgery, biological treatment and ATAD. This overview of treatment considerations is needed to allow physicians and patients to consider the different options in the context of providing optimal and personalized care for severe uncontrolled CRSwNP. In conclusion, the five major treatment options for severe uncontrolled CRSwNP have intrinsic advantages, specific indications and considerations that are of importance to the patient, the physician and the society. This EUFOREA statement supports the unmet need to define criteria for the indication of every treatment pillar of CRSwNP. [ABSTRACT FROM AUTHOR]

Introduction: SYNAPSE, a Phase III, randomised, doubleblind trial, assessed the efficacy of mepolizumab in severe chronic rhinosinusitis with nasal polyps (CRSwNP) (Han JK, et al. Lancet Respir Med 2021; S2213-2600(21)00097-7). Aim: To assess the clinical response to mepolizumab in severe CRSwNP. Method: In SYNAPSE, patients received standard of care plus mepolizumab (100 mg subcutaneous) or placebo for 52 weeks. This post hoc, descriptive analysis, classified patients in the intent-totreat (ITT) population without sinus surgery during the study period as responders, using 5 modified European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) criteria (Bachert C, et al. JACI, 2021;147:29). Results: In the ITT population (n=407), 381 and 343 patients had not had sinus surgery by Weeks 24 and 52, respectively. For each EUFOREA criterion (reduced nasal polyp size and nasal obstruction, improved sense of smell, improved quality of life, improved overall symptoms) proportion of patients classified as responders was higher with mepolizumab than placebo at Weeks 24 and 52. The proportion of patients who met =3 criteria was 55% with mepolizumab vs 35% with placebo at Week 24, and 67% vs 49% at Week 52. Conclusion: Clinical response, as defined by the modified EUFOREA criteria, was greater with mepolizumab than placebo and increased from Week 24 to Week 52, suggesting a sustained, progressive response in patients with severe CRSwNP without sinus surgery during the study. [ABSTRACT FROM AUTHOR]