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Objectives: To assess the severity of the top 5 22-item Sino-Nasal Outcome Test (SNOT-22) items ranked most important by patients with chronic rhinosinusitis with nasal polyps (CRSwNP), the effect of dupilumab on these items, and their association with objective disease measures., Study Design: Post hoc analysis of the SINUS-24 (NCT02912468) and SINUS-52 (NCT02898454) clinical trials., Setting: Multinational, multicenter, randomized, double-blind, placebo-controlled, parallel-group studies., Methods: Patients ranked the SNOT-22 items most affecting their health at baseline. Item symptom severity (0-5 scale) was assessed at baseline, Week 24 (W24), and Week 52 (W52). Changes in nasal polyps score (NPS) and Lund-Mackay (LMK) scores were assessed in patients with/without SNOT-22 items improvements of at least 1 severity group point at W24 and W52., Results: The SNOT-22 items ranked most important at baseline were "decreased sense of smell/taste" (87% of patients), followed by "nasal blockage" (82%), "postnasal discharge" (40%), "thick nasal discharge" (37%), and "wake up at night" (26%); 82%, 61%, 32%, 40%, and 26% of patients reported severe symptoms (score 4 or 5) for these items, respectively. Dupilumab improved score severity for all top 5 items versus placebo at W24 and W52. Improvements in NPS and LMK scores were numerically greater in patients with improvements in the SNOT-22 top 5 items., Conclusion: Loss of smell/taste was ranked as the most important symptom by patients with CRSwNP. Dupilumab reduced the severity of the top 5 most important SNOT-22 items versus placebo, in parallel with improvements in objective disease measures., Clinical Trial Registration: SINUS-24 and SINUS-52 clinical trials were registered with ClinicalTrials.gov, identifiers NCT02912468 and NCT02898454, respectively., (© 2023 The Authors. Otolaryngology‐Head and Neck Surgery published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngology‐Head and Neck Surgery Foundation.)

Background: This post hoc analysis of the international SINUS-24/-52 trials (NCT02912468/NCT02898454) aimed to assess dupilumab efficacy in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP) according to different definitions of type 2 inflammatory signature., Methods: Six definitions of type 2 inflammation were used: ≥150 eosinophils/μL or total immunoglobulin E (IgE) ≥100 IU/mL with a coexisting type 2 condition; ≥150 eosinophils/μL or total IgE ≥100 IU/mL; ≥150 eosinophils/μL; ≥250 eosinophils/μL or total IgE ≥100 IU/mL; coexisting asthma or ≥300 eosinophils/μL; presence of a coexisting type 2 condition. Odds ratios (ORs; dupilumab vs. placebo) for achieving clinically meaningful improvement (≥1 point) from baseline to week 24 (pooled SINUS-24/-52) and week 52 (SINUS-52) were calculated for nasal polyp score (NPS; range 0-8), nasal congestion/obstruction score (NC; 0-3), and loss of smell score (LoS; 0-3)., Results: At baseline (n = 724), most patients displayed a type 2 inflammatory signature across definitions (64.2%-95.3%). At week 24, ORs for clinically meaningful improvement ranged from 11.9 to 14.9 for NPS across type 2 definitions, 6.5-9.6 for NC, and 12.2-17.8 for LoS (all p < 0.0001). OR ranges were similar or greater at week 52: 19.0-36.6, 7.6-12.1, and 9.2-33.5, respectively (all p < 0.0001)., Conclusion: Most patients with CRSwNP in the SINUS study had type 2 inflammation. Dupilumab demonstrated robust efficacy across definitions of type 2 inflammation, consistent with its profile as an inhibitor of Interleukin-4 and Interleukin-13 signaling, key and central drivers of type 2 inflammation in CRSwNP., Key Points: This study assessed type 2 inflammation prevalence and dupilumab efficacy in chronic rhinosinusitis with nasal polyps according to algorithm-defined type 2 inflammation Dupilumab efficacy was similar across all type 2 definitions., (© 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.)

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a predominantly type 2 inflammatory disease, which often coexists with allergic rhinitis (AR). Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin-4 and interleukin-13, key and central drivers of type 2 inflammation. Objective: This post hoc analysis investigated the efficacy and safety of dupilumab in patients with severe CRSwNP with or without coexisting AR in the pooled phase III SINUS-24/SINUS-52 studies. Methods: Patients randomized to subcutaneous dupilumab 300 mg (n = 438) or placebo (n = 286) every 2 weeks for 24 (SINUS-24) or 52 weeks (SINUS-52) were analyzed. Pooled data from the first 24 weeks of treatment are presented. Changes from baseline in disease outcome measures and biomarker levels were analyzed by the patient-reported history of AR status. Results: Overall, 338 of 724 patients (46.7%) had AR. Baseline characteristics were generally similar between patients with and those without AR. Dupilumab significantly improved objective and patient-reported measures of CRSwNP, including loss of smell, and reduced systemic and nasal biomarker levels versus placebo at week 24, with no significant treatment difference between patients with and those without AR. Use of systemic corticosteroids and/or sinonasal surgery during treatment was significantly reduced with dupilumab versus placebo, irrespective of AR status (p ≤ 0.0029). The safety profile of dupilumab was similar in patients with and in patients without AR. Conclusion: Dupilumab demonstrated significant improvements in both clinical end points and symptom scores versus placebo in patients with severe CRSwNP, irrespective of comorbid AR status, a common subgroup of patients often associated with poorer CRSwNP outcomes. Clinical trials NCT02912468 (SINUS-24) and NCT02898454 (SINUS-52), www.clinicaltrials.gov.

Background: Transient increases in blood eosinophil counts have been observed in dupilumab clinical trials., Objective: To assess eosinophil counts and eosinophilia-related treatment-emergent adverse events (TEAEs) across 11 dupilumab clinical trials, comparing adult and adolescent patients with asthma and adult patients with chronic rhinosinusitis with nasal polyps (CRSwNP), atopic dermatitis, and eosinophilic esophagitis., Methods: Eosinophil counts, rates of eosinophilia-related TEAEs or treatment-emergent eosinophilia (>1,500 cells/μL), discontinuations, clinical symptoms, and efficacy in patients with asthma or CRSwNP with treatment-emergent eosinophilia are presented., Results: Transient increases in mean eosinophil counts were observed in dupilumab-treated patients with asthma (mean range across studies at baseline: 349-370 cells/μL; week 4: 515-578 cells/μL), CRSwNP (baseline: 440-448 cells/μL; week 16: 595 cells/μL), and atopic dermatitis (baseline: 434-600 cells/μL; week 4: 410-710 cells/μL), followed by a decline starting by week 24 to baseline or lower. No increases were seen in patients with eosinophilic esophagitis (baseline: 310 cells/μL; week 4: 230 cells/μL). In dupilumab-treated patients across all studies, rates of eosinophilia TEAEs were 0% to 13.6%. Clinical symptoms associated with increased eosinophils were rare (seven of 4,666 dupilumab-treated patients, including six cases of eosinophilic granulomatosis with polyangiitis) and occurred only in patients with asthma or CRSwNP. Eosinophilia was not associated with reduced dupilumab efficacy., Conclusions: Transient increases in eosinophil counts with dupilumab treatment did not affect efficacy and were rarely of clinical consequence. It remains important for physicians to base judgment on individual patient history and baseline eosinophil counts and to be alert to hypereosinophilic symptoms., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Patients with asthma and/or chronic rhinosinusitis with nasal polyps (CRSwNP) experience recurrent respiratory tract infections. Dupilumab targets type 2 inflammation, a common underlying pathophysiology of both conditions, with proven efficacy., Objective: To examine investigator-reported respiratory infection adverse events and anti-infective medication use with dupilumab versus placebo in patients with moderate-to-severe asthma or severe CRSwNP., Methods: We performed a post hoc analysis of the pivotal phase 3 trials LIBERTY ASTHMA QUEST (NCT02414854) and LIBERTY NP SINUS-52 (NCT02898454) in moderate-to-severe asthma and severe CRSwNP, respectively., Results: Investigator-reported respiratory infection events occurred at a significantly lower incidence in patients treated with dupilumab versus placebo, in both asthma (22% lower; P < .0001; 95% CI 0.71-0.85) and CRSwNP (38% lower; P <.0001; 95% CI 0.51-0.75). Reported upper and lower respiratory tract infection events were numerically or significantly lower in dupilumab-treated patients in both conditions, as were the number of patients experiencing investigator-reported infections. Significantly less systemic anti-infective medication use occurred in dupilumab versus placebo in asthma (24% lower; P < .0001; 95% CI 0.70-0.83) and CRSwNP patients (49% lower; P < .0001; 95% CI 0.43-0.61), and significantly fewer dupilumab-treated patients used anti-infective medications. When examined by season and month, the data indicated that investigator-reported respiratory infections and anti-infective medication use were less frequent in dupilumab- versus placebo-treated patients throughout the calendar year., Conclusions: Dupilumab treatment was associated with a reduced incidence of investigator-reported respiratory infections in patients with moderate-to-severe asthma or severe CRSwNP. Further studies are required to determine the mechanism behind this reduction., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Allergic rhinitis (AR) is a common health problem in the United States, with significant comorbidities and impairment of quality of life despite the availability of many prescription (Rx) and over-the-counter (OTC) medications. The health-care practitioners (HCPs) arm of the Current Allergic Rhinitis Experiences Survey (CARES) assessed HCPs' perceptions about the current management of AR. This U.S.-based national survey included 375 primary care physicians and 375 nurse practitioners/physician assistants. Participants were screened to ensure that they treat ≥15 AR sufferers per month during allergy season. The majority of HCPs (86%) agreed that AR patients can easily recognize allergy symptoms after diagnosis and that 57% of their patients come to them self-recognizing their symptoms. A total of 82% strongly agreed that AR sufferers are primarily diagnosed via history and physical and do not typically undergo diagnostic testing until after pharmacologic intervention. HCPs reported that 63-77% of AR sufferers can easily manage AR once treatment is established. According to surveyed HCPs, OTC medication should precede an Rx medication for AR management. A total of 82% HCPs considered intranasal steroids (INSs) to be the gold standard AR treatment and have minimal safety concerns about INS use. HCPs perceive that patients can easily recognize and self-manage their AR symptoms. Patient history/symptoms and physical examination are the primary methods of AR diagnosis. INSs are considered the gold standard for treatment of AR. However, most HCPs feel OTC medication should be tried before Rx medication for AR management. [ABSTRACT FROM AUTHOR]

Allergic rhinitis (AR) affects ∼60 million people in the United States. This study evaluates awareness, attitudes, and behaviors of AR sufferers on the management of their condition. This U.S.-based survey evaluated 1600 adult AR sufferers to assess their perceptions of AR diagnosis, treatment preferences, and interactions with health care practitioners (HCPs). Two consumer groups of AR sufferers were assessed: users of over-the-counter (OTC) medications only (n = 1020) and users of prescription (Rx) ± OTC medications (n = 580). The Rx group included 451 intranasal steroid (INS) users. Eighty-two percent of respondents indicated that they require minimal to no HCP guidance to manage AR; 51% had not visited an HCP in the past 2 years. Eighty-six percent of respondents agreed that they can self-recognize AR symptoms, and 69% suspected allergies before diagnosis. On suspecting nasal allergies, 52% of sufferers purchased an OTC medication. Seventy-two percent of AR sufferers said they are likely to go to an HCP if symptoms persist after they tried multiple OTC options. Rx users perceived INSs to be more beneficial in treating AR and showed a high level of satisfaction (a score of 7.4 out of 10). Forty-eight percent of AR sufferers felt the need for more efficacious OTC medications to better manage their AR symptoms. This study indicated that AR sufferers perceive that they self-recognize AR symptoms and initiate their management with OTC options. The availability of OTC medications did not deter AR sufferers from visiting HCPs for advice when symptoms worsen. Nonetheless, more efficacious OTC options are still desired. [ABSTRACT FROM AUTHOR]