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Competing Interests: Disclosures The authors have no conflicts of interest to report.

Background: Nasal polyps (NPs) are commonly associated with chronic rhinosinusitis (CRS). In keeping with the unified airway hypothesis, asthma and CRS with NP (CRSwNP) frequently co-occur, share a similar pathophysiology, and are often treated with oral corticosteroids (OCS); however, a need for alternative treatment options for patients with comorbid asthma and CRSwNP remains., Objective: To characterize the short- and long-term dual airway effectiveness of the anti-interleukin-5 monoclonal antibody, mepolizumab, in real-world patients with asthma and comorbid NP., Methods: Adult patients with CRSwNP who initiated mepolizumab from November 1, 2014, to September 30, 2021, were identified from 2 Merative MarketScan Research Databases. Outcomes were compared for the 12 months pre- and post-mepolizumab initiation and a variable follow-up period. Primary outcomes included the following: annual rate and proportion of patients with NP- and asthma-related exacerbations; NP surgery occurrences; all-cause OCS claims, number of OCS bursts, and daily OCS dose; all-cause and NP-related health care resource utilization., Results: During the 12 months post-index, patients experienced fewer NP- and asthma-related exacerbations, required fewer sinus surgeries, and reduced use of OCS, with fewer all-cause OCS claims and OCS bursts. Significant reductions in asthma exacerbation-related and NP-related health care resource utilization were also observed., Conclusion: This study illustrated the near- and long-term real-world effectiveness of mepolizumab treatment, with a focus on dual lower and upper airway benefit from single-agent add-on therapy. These results may aid physicians in clinical decision-making for patients with asthma and comorbid CRSwNP with complex care needs., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Asthma is a prevalent health concern among Illinois (IL) children, and management is significantly influenced by social determinants. There were 17 states who have adopted stock inhaler laws, but implementation varies widely., Objective: To assess critical barriers to implementation and address sustainability of stock inhaler programming in school-based asthma care in IL., Methods: Semistructured interviews were conducted with high asthma burden school districts in IL to assess barriers in implementing stock inhaler policies and resultant programming. Thematic analysis was performed using Atlas.ti (Scientific Software Development GmbH, Berlin, Germany) to identify and code "threats" to future sustainability. Data were synthesized and presented to stakeholders for barrier mitigation. A schematic flowchart outlining steps to support sustainability was created., Results: A total of 18 interviews were conducted with key community partners across 8 IL school districts, representing rural, urban, and suburban areas. Analysis revealed 25 barriers, with several identified as "threats" to future sustainability, including liability concerns, follow-up care assurance, funding/resources, pharmacy dispensing practices, district-level readiness to change, and nurse staffing. Stakeholders formed a statewide coalition to address these barriers, increase awareness, plan evaluations, and advise on state funding allocation. A national stock inhaler toolkit tailored to school administrative needs was developed to support sustainability efforts., Conclusion: Strategic stakeholder and community engagement are vital for establishing and sustaining stock inhaler programs that adhere to policy mandates. Many districts face challenges initiating and maintaining such programs without critical barrier mitigation and support. Collaborative solutions are necessary to ensure effective school-based asthma management and mitigate persistent pediatric asthma health disparities., (Copyright © 2024 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Disclosures Dr Philipenko has received speaking honoraria from Covis pharma, GlaxoSmithKline, AstraZeneca, and Regeneron Pharmaceuticals and fees from AstraZeneca and Sanofi for serving on advisory boards. Dr Cockcroft and Dr Davis have no conflicts of interest to report.

Background: Long-term tezepelumab treatment in the DESTINATION study (NCT03706079) resulted in reduced asthma exacerbations, reduced biomarker levels, and improved lung function and symptom control in patients with severe, uncontrolled asthma., Objective: To explore the time course of changes in biomarkers and clinical manifestations after treatment cessation after 2 years of tezepelumab treatment., Methods: DESTINATION was a 2-year, phase 3, multicenter, randomized, placebo-controlled, double-blind study of tezepelumab treatment in patients (12-80 years old) with severe asthma. Patients received their last treatment doses at week 100 and could enroll in an extended follow-up period from weeks 104 to 140. Change over time in key biomarkers and clinical outcomes were assessed in tezepelumab vs placebo recipients for 40 weeks after stopping treatment., Results: Of 569 patients enrolled in the extended follow-up period, 426 were included in the analysis (289 received tezepelumab and 137 placebo). In the 40-week period after the last tezepelumab dose, blood eosinophil counts, fractional exhaled nitric oxide levels, and Asthma Control Questionnaire-6 scores gradually increased from weeks 4 to 10, with a gradual reduction in pre-bronchodilator forced expiratory volume in 1 second such that blood eosinophil counts, fractional exhaled nitric oxide levels, and clinical outcomes returned to placebo levels; however, none of these outcomes returned to baseline levels. Total IgE levels increased later from week 28 and remained well below placebo and baseline levels during the 40-week period after the last tezepelumab dose., Conclusion: This analysis reveals the benefits of continued tezepelumab treatment in the management of patients with severe, uncontrolled asthma, compared with stopping treatment after 2 years., Trial Registration: ClinicalTrials.gov Identifier: NCT03706079., Competing Interests: Disclosures Prof Brightling has received grants and consultancy fees from 4D Pharma, Areteia Therapeutics, AstraZeneca, Chiesi, Genentech, GSK, Global Access Diagnostics (formerly Mologic), Novartis, Regeneron Pharmaceuticals, Roche, and Sanofi. Dr Caminati has received fees from AstraZeneca for serving on advisory boards and has received speaker fees from GSK and Sanofi. Dr Llanos and Dr Caveney are employees of Amgen and own stock in Amgen. Dr Kotalik, Dr Lundahl, Ms Gołąbek, Dr Martin, and Dr Ponnarambil are employees of AstraZeneca and may own stock or stock options in AstraZeneca. Dr Griffiths was an employee of AstraZeneca at the time of the study. Prof Israel has served as a consultant to and received personal fees from 4D Pharma, AB Science, Amgen, AstraZeneca, Avillion, Biometry, Cowen, Equillium, Genentech, GSK, Merck, Novartis, Pneuma Respiratory, PPS Health, Regeneron Pharmaceuticals, Sanofi, Sienna Biopharmaceuticals, and Teva Pharmaceuticals; has received nonfinancial support from Circassia Pharmaceuticals, Teva Pharmaceuticals, and Vorso Corp; and has received clinical research grants from AstraZeneca, Avillion, Genentech, Gossamer Bio, Novartis, and Sanofi. Prof Pavord has received speaker fees from Aerocrine AB, Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Novartis, Regeneron Pharmaceuticals, Sanofi, and Teva Pharmaceuticals; has received payments for organization of educational events from AstraZeneca, GSK, Regeneron Pharmaceuticals, Sanofi, and Teva Pharmaceuticals; has received consultancy fees from Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, Circassia Pharmaceuticals, Dey Pharma, Genentech, GSK, Knopp Biosciences, Merck, MSD, Napp Pharmaceuticals, Novartis, Regeneron Pharmaceuticals, RespiVert, Sanofi, Schering-Plough, and Teva Pharmaceuticals; has received international scientific meeting sponsorship from AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Napp Pharmaceuticals, Regeneron Pharmaceuticals, Sanofi, and Teva Pharmaceuticals; and has received a research grant from Chiesi. Prof Wechsler has received consulting, advisory or speaker fees from Amgen, Areteia Therapeutics, AstraZeneca, Avalo Therapeutics, Boehringer Ingelheim, Celldex Therapeutics, Cellergy Pharma, Cerecor, CytoReason, Eli Lilly, Equillium, GSK, Incyte, Kinaset Therapeutics, Merck, Novartis, Om Pharma, Overtone Therapeutics/Foresite Labs, Phylaxis Bioscience, PULMATRiX, Rapt Therapeutics, Regeneron Pharmaceuticals, Roche/Genentech, Sanofi/Genzyme, Sentien Biotechnologies, Sound Biologics, Tetherex Pharmaceuticals, Teva Pharmaceuticals, Upstream Bio and Verona Pharma. Prof Porsbjerg has received grants and consultancy fees from ALK-Abelló, AstraZeneca, Chiesi, GSK, Novartis, Sanofi, and Teva Pharmaceuticals. Dr Corren has received grants and personal fees from AstraZeneca, Genentech, and Vectura; and has received grants from Optinose, Sanofi, and Teva Pharmaceuticals., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The use of single-combination inhaled corticosteroid and long-acting bronchodilator for maintenance and relief therapy (MART) significantly reduces asthma exacerbations and has been incorporated into asthma guidelines since December 2020, but there are limited data regarding the implementation of this approach to asthma management., Objective: To determine the frequency at which MART was recommended to patients with moderate-to-severe asthma being seen at subspecialty pulmonary and allergy practices at an academic healthcare system, and the patient and clinician characteristics associated with the use of MART., Methods: We conducted a retrospective cross-sectional study of the electronic medical records of an academic healthcare system in the Northeastern United States between January 2021 and October 2023. Patient demographic and clinician data were collected, and MART recommendation was confirmed by chart review. We assessed the relationships among patient demographics, clinician characteristics, and MART recommendation., Results: Of 2016 patients reviewed, 293 (14.5%) were recommended MART, with 255 (87%) concurrently prescribed short-acting bronchodilators. Patients on inhaled corticosteroid-formoterol at baseline were significantly more likely to be recommended MART, whereas older patients and those on Medicare were significantly less likely to be recommended MART; 22 of 50 clinicians (44%) did not recommend MART ever, and only 3 clinicians recommended MART to 30% to 60% of their patients. Clinicians who were part of the asthma group were significantly more likely to recommend MART., Conclusion: Among academic subspecialty clinicians, there has been limited implementation of MART, with a small number of clinicians adopting MART routinely and more than 40% of clinicians not recommending it., Competing Interests: Disclosures Dr Zaeh has received consulting fees from AstraZeneca. Dr Chupp has received Honoraria and consultancy fees from Amgen, AstraZeneca, Boehringer Ingelheim, Genentech, GlaxoSmithKline, Novartis, Regeneron Pharmaceuticals, Sanofi Genzyme, RAPT therapeutics, and Kymera. The remaining authors have no conflicts of interest to report., (Copyright © 2024 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Asthma control assessment is based on impairment (current symptoms) and risk (exacerbation history)., Objective: To understand the extent of uncontrolled asthma, we assessed relationships between prescription fills for systemic corticosteroids (SCS) and short-acting β 2 -agonists (SABA) as risk and impairment markers, respectively., Methods: Annual SCS and SABA fills among US patients with asthma were evaluated by a retrospective analysis of the IQVIA Longitudinal Access and Adjudication Data. Patients' disease severity was assigned based on the Global Initiative for Asthma step-therapy level. Exacerbations were evaluated by SCS fills within 12 months of a first asthma prescription fill. Uncontrolled asthma was defined as 2 or more SCS and/or 3 or more SABA fills annually. Individual patient relationships between SCS and SABA fills were assessed using Pearson's correlation coefficients., Results: A total of 4,506,527 patients were included; 15.1% had 2 or more SCS fills, 29.1% had 3 or more SABA fills, and 37.4% fulfilled either or both criteria. If only SCS use was assessed, 21.4% of cases that were treated as mild to moderate and 27.6% that were treated as severe asthma would have been misclassified as controlled. If only SABA use was evaluated, 7.8% of cases treated as mild to moderate and 11.2% treated as severe asthma would have been misclassified. Overall, 80.9% of uncontrolled asthma occurred in patients treated for mild to moderate disease. Among patients with 2 or more SCS fills, the mean SABA fills were 2.9; the correlation between SCS and SABA fills per patient was significant but weak (r = 0.18; P < .001)., Conclusion: High symptom burden and SCS exposures are not limited to severe asthma but are also characteristic of patients treated for mild to moderate disease. Both impairment and risk assessments are required to understand the full extent of uncontrolled asthma across disease severities., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Disclosures Dr Borish reports receiving investigator-initiated research grants from Regeneron (all funds are awarded to the University of Virginia) and serving on advisory boards for Sanofi/Genzyme, Regeneron, and AstraZeneca. Dr Harris reports serving on advisory boards for Regeneron and Cecelia Health.

Competing Interests: Disclosures Dr Anderson has served on advisory boards for Sanofi/Genzyme, Regeneron, and Genentech and has received grant funding from the COPIC Medical Foundation and Colorado Medicaid Supplemental Funding Program. The remaining authors have no conflicts of interest to report.

Background: There is little agreement on clinically useful criteria for identifying real-world responders to biologic treatments for asthma., Objective: To investigate the impact of pre-biologic impairment on meeting domain-specific biologic responder definitions in adults with severe asthma., Methods: This was a longitudinal, cohort study across 22 countries participating in the International Severe Asthma Registry (https://isaregistries.org/) between May 2017 and January 2023. Change in 4 asthma domains (exacerbation rate, asthma control, long-term oral corticosteroid [LTOCS] dose, and lung function) was assessed from biologic initiation to 1 year post-treatment (minimum 24 weeks). Pre- to post-biologic changes for responders and nonresponders were described along a categorical gradient for each domain derived from pre-biologic distributions (exacerbation rate: 0 to 6+/y; asthma control: well controlled to uncontrolled; LTOCS: 0 to >30 mg/d; percent-predicted forced expiratory volume in 1 second [ppFEV 1 ]: <50% to ≥80%)., Results: Percentage of biologic responders (ie, those with a category improvement pre- to post-biologic) varied by domain and increased with greater pre-biologic impairment, increasing from 70.2% to 90.0% for exacerbation rate, 46.3% to 52.3% for asthma control, 31.1% to 58.5% for LTOCS daily dose, and 35.8% to 50.6% for ppFEV 1 . The proportion of patients having improvement post-biologic tended to be greater for anti-IL-5/5R compared with for anti-IgE for exacerbation, asthma control, and ppFEV 1 domains, irrespective of pre-biologic impairment., Conclusion: Our results provide realistic outcome-specific post-biologic expectations for both physicians and patients, will be foundational to inform future work on a multidimensional approach to define and assess biologic responders and response, and may enhance appropriate patient selection for biologic therapies., Trial Registration: The ISAR database has ethical approval from the Anonymous Data Ethics Protocols and Transparency (ADEPT) committee (ADEPT0218) and is registered with the European Union Electronic Register of Post-Authorization studies (ENCEPP/DSPP/23720). The study was designed, implemented, and reported in compliance with the European Network Centres for Pharmacoepidemiology and Pharmacovigilance (ENCEPP) Code of Conduct (EUPAS38288) and with all applicable local and international laws and regulation, and registered with ENCEPP (https://www.encepp.eu/encepp/viewResource.htm?id=38289). Governance was provided by ADEPT (registration number: ADEPT1220)., Competing Interests: Disclosures Dr Perez-de-Llano reports grants, personal fees and non-financial support from AstraZeneca, personal fees and non-financial support from GlaxoSmithKline, grants, personal fees and non-financial support from Teva, personal fees and non-financial support from Chiesi, grants, personal fees and non-financial support from Sanofi, personal fees from MSD, personal fees from Techdow Pharma, grants, personal fees and non-financial support from Faes Farma, personal fees from Leo-Pharma, grants and personal fees from Gebro, personal fees from Gilead, outside the submitted work. Dr Scelo is a consultant for Observational and Pragmatic Research Institute (OPRI). OPRI conducted this study in collaboration with Optimum Patient Care and AstraZeneca. Dr Canonica has received research grants and lecture or advisory board fees from Menarini, Alk-Albello, Allergy Therapeutics, Anallergo, AstraZeneca, MedImmune, Boehringer Ingelheim, Chiesi Farmaceutici, Circassia, Danone, Faes, Genentech, Guidotti Malesci, GlaxoSmithKline, Hal Allergy, Merck, Merck Sharp & Dohme, Mundipharma, Novartis, Orion, Sanofi Aventis, Sanofi, Genzyme/Regeneron, Stallergenes, UCB Pharma, Uriach Pharma, Teva, Thermo Fisher, and Valeas. Dr Henley is affiliated with OPRI and reports receiving travel support from Eisai Limited. Dr Larenas-Linnemann reports receiving personal fees from ALK-Abelló, AstraZeneca national and global, Bayer, Chiesi, Grunenthal, Grin, GlaxoSmithKline national and global, Viatris, Menarini, Merck Sharp & Dohme, Novartis, Pfizer, Sanofi, Siegfried, UCB, Carnot, grants from AbbVie, Bayer, Lilly, Sanofi, AstraZeneca, Pfizer, Novartis, Circassia, UCB, and GlaxoSmithKline, outside the submitted work. Dr Peters declares receiving personal fees and nonfinancial support from AstraZeneca, GlaxoSmithKline, and Sanofi. Dr Pfeffer has attended advisory boards for AstraZeneca, GlaxoSmithKline, and Sanofi; has given lectures at meetings supported by AstraZeneca and GlaxoSmithKline; has taken part in clinical trials sponsored by AstraZeneca, GlaxoSmithKline, Novartis, and Sanofi, for which his institution received remuneration; and has a current research grant funded by GlaxoSmithKline. Dr Tran is an employee of AstraZeneca and may own stock or stock options in AstraZeneca. Dr Suppli Ulrik reports receiving personal fees for talks and having participation in advisory boards and others from AstraZeneca, GlaxoSmithKline, TEVA, Boehringer Ingelheim, Orion Pharma, Sanofi Genzyme, TFF Pharmaceuticals, Covis Pharma, Berlin-Chemie, Takeda, Chiesi, and Pfizer, outside the submitted work. Dr Popov declares relevant research support from Novartis and Chiesi Pharma. Dr Sadatsafavi has received honoraria from AstraZeneca, Boehringer Ingelheim, TEVA, and GlaxoSmithKline for purposes unrelated to the content of this manuscript and has received research funding from AstraZeneca and Boehringer Ingelheim directly into his research account from AstraZeneca for unrelated projects. Dr Hew declares receiving grants and other advisory board fees (made to his institutional employer) from AstraZeneca, GlaxoSmithKline, Novartis, Sanofi, Teva, and Seqirus, for unrelated projects. Dr Maspero reports receiving speaker fees and grants or serving on the advisory boards for AstraZeneca, Sanofi, GlaxoSmithKline, Novartis, Inmunotek, Menarini, and Noucor. Dr Gibson has received speaker fees and grants to his institution from AstraZeneca, GlaxoSmithKline, and Novartis. Dr FitzGerald previously declared receiving grants from AstraZeneca, GlaxoSmithKline, Sanofi Regeneron, and Novartis paid directly to UBC and receiving personal fees for lectures and attending advisory boards for AstraZeneca, GlaxoSmithKline, Sanofi Regeneron, and TEVA. Dr Torres-Duque has received fees as advisory board participant and/or speaker from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, and Sanofi-Aventis; has taken part in clinical trials from AstraZeneca, Novartis, and Sanofi-Aventis; and has received unrestricted grants for investigator-initiated studies at Fundacion Neumologica Colombiana from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Grifols, and Novartis. Dr Porsbjerg has attended advisory boards for AstraZeneca, Novartis, TEVA, and Sanofi-Genzyme; has given lectures at meetings supported by AstraZeneca, Novartis, TEVA, Sanofi-Genzyme, and GlaxoSmithKline; has taken part in clinical trials sponsored by AstraZeneca, Novartis, Merck Sharp & Dohme, Sanofi-Genzyme, GlaxoSmithKline, and Novartis; and has received educational and research grants from AstraZeneca, Novartis, TEVA, GlaxoSmithKline, ALK, and Sanofi-Genzyme. Dr Papadopoulos has been a speaker and/or advisory board member for Abbott, AbbVie, ALK, Asit Biotech, AstraZeneca, Biomay, Boehringer Ingelheim, GlaxoSmithKline, HAL, Faes Farma, Medscape, Menarini, Merck Sharp & Dohme, Novartis, Nutricia, OM Pharma, Regeneron, Sanofi, Takeda, and Viatris. Dr Papaioannou has received fees and honoraria from Menarini, GlaxoSmithKline, Novartis, Elpen, Boehringer Ingelheim, AstraZeneca, and Chiesi. Dr Heffler declares receiving personal fees from Sanofi, Regeneron, GlaxoSmithKline, Novartis, AstraZeneca, Stallergenes, and Circassia. Dr Iwanaga received lecture fees from Kyorin, GlaxoSmithKline, Novartis, Boehringer Ingelheim, and AstraZeneca. Dr Al-Ahmad has received advisory board and speaker fees from AstraZeneca, Sanofi, Novartis, and GlaxoSmithKline and received a grant from Kuwait Foundation for the Advancement of Sciences. Dr Kuna reports receiving personal fees from Adamed, AstraZeneca, Berlin Chemie Menarini, FAES, Glenmark, Novartis, Polpharma, Boehringer Ingelheim, Teva, and Zentiva, outside the submitted work. Dr Fonseca reports receiving grants from research agreements with AstraZeneca, Mundipharma, Sanofi Regeneron, and Novartis and personal fees for lectures and attending advisory boards for AstraZeneca, GlaxoSmithKline, Mundipharma, Novartis, Sanofi Regeneron, and TEVA. Dr Al-Lehebi has given lectures at meetings supported by AstraZeneca, Boehringer Ingelheim, Novartis, GlaxoSmithKline, and Sanofi and participated in advisory board fees from GlaxoSmithKline, AstraZeneca, Novartis, and Abbott. Dr Rhee received consulting/lecture fees from Merck Sharp & Dohme, AstraZeneca, GlaxoSmithKline, Novartis, Takeda, Mundipharma, Boehringer Ingelheim, Teva, Sanofi, and Bayer. Dr Koh reports receiving grant support from AstraZeneca and honoraria for lectures and advisory board meetings paid to her hospital (Singapore General Hospital) from GlaxoSmithKline, AstraZeneca, Novartis, Sanofi, and Boehringer Ingelheim, outside the submitted work. Dr Cosio declares receiving grants from Chiesi and GlaxoSmithKline; personal fees for advisory board activities from Chiesi, GlaxoSmithKline, Novartis, Sanofi, Teva, and AstraZeneca; and payment for lectures/speaking engagements from Chiesi, Novartis, GlaxoSmithKline, Menarini, and AstraZeneca, outside the submitted work. Dr Perng (Steve) has received sponsorship to attend or speak at international meetings, honoraria for lecturing or attending advisory boards, and research grants from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Daiichi Sankyo, Shionogi, and Orient Pharma. Dr Menzies-Gow is an employee of AstraZeneca and may own stock or stock options in AstraZeneca. Dr Jackson has received speaker fees and consultancy fees from AstraZeneca, GlaxoSmithKline, Sanofi Regeneron, and Boehringer Ingelheim and research funding from AstraZeneca. Dr Busby has received research grants from AstraZeneca and personnel fees from NuvoAir, outside the submitted work. Dr Heaney has received grant funding, participated in advisory boards, and given lectures at meetings supported by Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, Circassia, Hoffmann-La Roche, GlaxoSmithKline, Novartis, Theravance, Evelo Biosciences, Sanofi, and Teva; has received grants from MedImmune, Novartis United Kingdom, Roche/Genentech Inc, GlaxoSmithKline, Amgen, Genentech/Hoffman-La Roche, AstraZeneca, MedImmune, Aerocrine, and Vitalograph; has received sponsorship for attending international scientific meetings from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, and Napp Pharmaceuticals; has taken part in asthma clinical trials sponsored by AstraZeneca, Boehringer Ingelheim, Hoffmann-La Roche, and GlaxoSmithKline for which his institution received remuneration; and is the Academic Lead for the Medical Research Council Stratified Medicine United Kingdom Consortium in Severe Asthma which involves industrial partnerships with a number of pharmaceutical companies including Amgen, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Hoffmann-La Roche, and Janssen. Dr Patel has received advisory board and speaker fees from AstraZeneca, GlaxoSmithKline, Novartis, and Sanofi/Regeneron. Dr Wang has received honoraria from AstraZeneca, GlaxoSmithKline, and Genentech; has been an investigator on studies sponsored by AstraZeneca, GlaxoSmithKline, Genentech, Sanofi, Novartis, and Teva, for which her institution has received funding. Dr Wechsler reports receiving grants and/or personal fees from Novartis, Sanofi, Regeneron, Genentech, Sentien, Restorbio, Equillium, Genzyme, Cohero Health, Teva, Boehringer Ingelheim, AstraZeneca, Amgen, GlaxoSmithKline, Cytoreason, Cerecor, Sound Biologics, Incyte, and Kinaset. Dr Altraja has received lecture fees from AstraZeneca, Boehringer Ingelheim, Berlin-Chemie Menarini, GlaxoSmithKline, Merck Sharp & Dohme, Norameda, Novartis, Orion, Sanofi, and Zentiva; has sponsorships from AstraZeneca, Boehringer Ingelheim, Berlin-Chemie Menarini, GlaxoSmithKline, Merck Sharp & Dohme, Norameda, Novartis, and Sanofi; and has participated in advisory boards for AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Sanofi, and Teva. Dr Lehtimäki has received personal fees from ALK, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Menarini, Novartis, Orion Pharma, and Sanofi. Dr Bourdin has received industry-sponsored grants from AstraZeneca/MedImmune, Boehringer Ingelheim, Cephalon/Teva, GlaxoSmithKline, Novartis, and Sanofi-Regeneron and conducted consultancies with AstraZeneca/MedImmune, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Regeneron-Sanofi, Med-in-Cell, Actelion, Merck, Roche, and Chiesi. Dr Bjermer has (in the last 3 years) received lecture or advisory board fees from Alk-Abello, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Mundipharma, Novartis, Sanofi, Genzyme/Regeneron, and Teva. Ms Bulathsinhala is an employee of the OPRI. OPRI conducted this study in collaboration with Optimum Patient Care and AstraZeneca. Ms Carter is an employee of Optimum Patient Care, which is a co-funder of the International Severe Asthma Registry. Dr Murray is a consultant for OPRI. OPRI conducted this study in collaboration with Optimum Patient Care and AstraZeneca. Mr Beastall is an employee of the Optimum Patient Care Global, a co-funder of the International Severe Asthma Registry. Dr Denton declares receiving grants to her institution from AstraZeneca, GlaxoSmithKline, Novartis, Sanofi, Teva, and Seqirus, for unrelated projects and speaker fees from Sanofi. Dr Price has advisory board membership with AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, Viatris, and Teva Pharmaceuticals; consultancy agreements with AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, Viatris, and Teva Pharmaceuticals; grants and unrestricted funding for investigator-initiated studies (conducted through OPRI Pte Ltd) from AstraZeneca, Chiesi, Viatris, Novartis, Regeneron Pharmaceuticals, Sanofi Genzyme, and United Kingdom National Health Service; payment for lectures/speaking engagements from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, Commune Digital, GlaxoSmithKline, Medscape, Viatris, Novartis, Regeneron Pharmaceuticals and Sanofi Genzyme, and Teva Pharmaceuticals; payment for travel/accommodation/meeting expenses from AstraZeneca, Boehringer Ingelheim, Novartis, Medscape, and Teva Pharmaceuticals; stock/stock options from AKL Research and Development Ltd which produces phytopharmaceuticals; owns 74% of the social enterprise Optimum Patient Care Ltd (Australia and United Kingdom) and 92.61% of OPRI Pte Ltd (Singapore); 5% shareholding in Timestamp which develops adherence monitoring technology; is peer reviewer for grant committees of the United Kingdom Efficacy and Mechanism Evaluation Programme and Health Technology Assessment; and was an expert witness for GlaxoSmithKline. The remaining authors have no conflicts of interest to report., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Although various monoclonal antibodies have been used as add-on therapy for severe eosinophilic asthma (SEA), to the best of our knowledge, no direct head-to-head comparative study has evaluated their efficacy., Objective: To compare the efficacy of reslizumab, mepolizumab, and dupilumab in patients with SEA., Methods: This was a multicenter, prospective observational study in patients with SEA who had received 1 of these biologic agents for at least 6 months. Cox proportional hazard models were used to compare the risk of the first exacerbation event, adjusting for sputum or blood eosinophils and common asthma-related covariates. The annual exacerbation rate was analyzed using a negative binomial model, and a mixed-effect model was used to analyze changes in forced expiratory volume in 1 second and asthma control test score over time., Results: A total of 141 patients with SEA were included in the analysis; 71 (50%) received dupilumab; 40 (28%) received reslizumab, and 30 (21%) received mepolizumab. During the 12-month follow-up, 27.5%, 43.3%, and 38.0% of patients in the reslizumab, mepolizumab, and dupilumab groups, respectively, experienced at least 1 exacerbation. However, after adjusting for confounding factors, the dupilumab and mepolizumab groups showed similar outcomes in time-to-first exacerbation, exacerbation rate, forced expiratory volume in 1 second, and asthma control test score to those of the reslizumab group., Conclusion: In patients with SEA, treatment with reslizumab, mepolizumab, and dupilumab resulted in comparable clinical outcomes within a 12-month period., Trial Registration: The cohort protocol was sanctioned by the Institutional Review Board of each study center (clinicaltrial.gov identifier NCT05164939)., Competing Interests: Disclosures The authors have no conflicts of interest to report., (Copyright © 2023 American College of Allergy, Asthma & Immunology. All rights reserved.)

Background: Cost-related nonadherence to medications can be a barrier to asthma management., Objective: To quantify the impact of public drug plan deductibles on adherence to asthma medications., Methods: We used a quasi-experimental regression discontinuity analysis to determine whether thresholds in deductibles for public drug coverage, determined on the basis of annual household income, decreased medication use among lower-income children and adults with asthma in British Columbia from 2013 to 2018. Using dispensed medication records, we evaluated deductible thresholds at annual household incomes of $15,000 (a deductible increase from 0% to 2% of annual household income), and $30,000 (a deductible increase from 2% to 3% annual household income). We evaluated medication costs, use, the ratio of inhaled corticosteroids-containing controller medications to total medications, excessive use of short-acting β-agonists, and the proportion of days covered by controller therapies. All costs are reported in 2020 Canadian dollars., Results: Overall, 88,935 individuals contributed 443,847 person-years of follow-up (57% of female sex, mean age 31 years). Public drug subsidy decreased by -$41.74 (95% CI, -$28.34 to -$55.13) at the $15,000-deductible threshold, a 28% reduction, and patient costs increased by $48.45 (95% CI, $35.37-$61.53). The $30,000 deductible threshold did not affect public drug costs (P = .31), but patient costs increased by $27.65 (95% CI, $15.22-$40.09), which is an 11% increase. Asthma-related medication use, inhaled corticosteroids-to-total medication ratio, excessive use of short-acting β-agonists, and proportion of days covered by controller therapies were not impacted by deductible thresholds., Conclusion: Income-based deductibles reduced public drug costs with no effect on asthma-related medication use, adherence to controller therapies, or excessive reliever therapy use in lower-income individuals with asthma., Competing Interests: Disclosures Dr Law has received research funding from the British Columbia Ministry of Health; has consulted for Health Canada, the Canadian Agency for Drugs and Technologies in Health, and iTAD Ltd; and has been an expert witness for the Federation of Postsecondary Educators. The remaining authors have no conflicts of interest to report., (Copyright © 2023 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the current evidence, its limitations, and future research directions for the use of biologics in pediatric asthma, with a particular focus on the potential use of biologics to prevent pediatric asthma and equity issues in access to biologic treatment and research participation., Data Sources: PubMed articles about the use of biologics in pediatric asthma were searched up to May 2023., Study Selections: Recent (2019-2023) original research articles and reviews were prioritized., Results: Although there are now 5 U.S. Food and Drug Administration-approved biologics for use in pediatric asthma, there are important knowledge gaps that ongoing research seeks to address, which include (1) the long-term efficacy and safety of using biologics in children, (2) the comparative efficacy of different biologics, (3) multi-omics-based classification of asthma endotypes and phenotypes in children to find potential new therapeutic targets and enable identification and validation of new biomarkers that may predict and help monitor response to treatment, and (4) whether starting biologics in early childhood can modify the natural history of asthma and potentially prevent asthma development., Summary: To promote equitable access to biologics and optimize asthma outcomes, future research should recruit patients across the full spectrum of socioeconomic and racial/ethnic backgrounds. Large-scale national and international collaborations between asthma researchers and clinicians are also necessary to fully understand the role of biologics in pediatric asthma., Competing Interests: Disclosures The authors have no conflicts of interest to report., (Copyright © 2023 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Asthma exacerbation frequencies vary throughout the year owing to seasonal triggers. Tezepelumab is a human monoclonal antibody that targets thymic stromal lymphopoietin. In the phase 3 NAVIGATOR study (NCT03347279), tezepelumab significantly reduced the annualized asthma exacerbation rate (AAER) vs placebo in patients with severe, uncontrolled asthma., Objective: To evaluate the effect of tezepelumab on asthma exacerbations across all seasons in NAVIGATOR patients (post hoc)., Methods: NAVIGATOR was a multicenter, randomized, double-blind, placebo-controlled study. Patients (12-80 years old) were randomized 1:1 to tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 52 weeks. AAER over 52 weeks was assessed by season. Data from patients in the Southern Hemisphere were transformed to align with Northern Hemisphere seasons., Results: Tezepelumab reduced the AAER vs placebo by 63% (95% confidence interval [CI], 52-72) in winter, 46% (95% CI, 26-61) in spring, 62% (95% CI, 48-73) in summer, and 54% (95% CI, 41-64) in fall. In matched climates, during the spring allergy season (March 1 to June 15) and ragweed allergy season (September), tezepelumab reduced the AAER vs placebo in patients with seasonal allergy by 59% (95% CI, 29-77) and 70% (95% CI, 33-87), respectively. In patients with perennial allergy and in those with seasonal allergy, tezepelumab reduced the AAER vs placebo across all seasons., Conclusion: Tezepelumab reduced exacerbations across all seasons vs placebo in patients with severe, uncontrolled asthma, including patients with seasonal and perennial allergies. These data further support the efficacy of tezepelumab in a broad population of patients with severe, uncontrolled asthma., Trial Registration: ClinicalTrials.gov Identifier: NCT03347279 (https://clinicaltrials.gov/ct2/show/NCT03347279)., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Patient adherence to biologic therapies is crucial for clinical benefits. Previous assessments of US patient adherence to severe asthma (SA) biologic therapies have relied on health care insurance claims data that have limitations., Objective: To describe real-world, specialist-reported, biologic administration and adherence among US adults with SA., Methods: CHRONICLE (ClinicalTrials.gov identifier: NCT03373045) is an ongoing real-world, noninterventional study of patients with SA treated by US subspecialists. Sites report date and location for all biologic administrations. We evaluated biologic (benralizumab, dupilumab, mepolizumab, omalizumab, reslizumab) adherence as the proportion of days covered (PDC) during the first 52 weeks and the mean number of days until patients received the expected number of doses for 13, 26, and 52 weeks of treatment., Results: A total of 2117 patients received biologic administrations between February 2018 and February 2022. Most patients (84%) received biologic administrations at a subspecialist site. Over time, administrations at specialist sites decreased, whereas at-home administrations increased. The median PDC was 87%; the mean number of days to receive a 52-week (364-day) equivalent number of doses was 423 for all biologics (average delay of 58 days). Dupilumab had the lowest PDC and highest mean delays in dosing across all intervals; better adherence was observed among commercially insured patients., Conclusion: Patients with SA are mostly adherent to biologic therapies. Biologics with shorter dosing intervals and at-home administration had worse adherence, likely because of greater opportunities for delays. Specialist-reported administration data provide a unique perspective on biologic adherence, which may be overestimated for at-home administrations by insurance claims data., Clinical Trial Registration: ClinicalTrials.gov: NCT03373045., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Airway hyperresponsiveness refers to an exaggerated bronchial constrictor response to a given exogenous inhaled agent and is governed by airway smooth muscle along with mucosal inflammation in asthma. In recent years, the advent of biologics and antialarmins has transformed severe asthma treatment in terms of reducing oral-corticosteroid-requiring exacerbations and improving disease control, asthma quality of life, and spirometry-measured lung function. In contrast, there have been comparatively fewer studies investigating the efficacy of biologics in airway hyperresponsiveness. In this focused review, we summarize the existing evidence base in this area regarding omalizumab, mepolizumab, benralizumab, and tezepelumab., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Patients with severe asthma (SA) experience a high disease burden, often precipitated by exposure to disease triggers., Objective: To evaluate the prevalence and effects of patient-reported triggers on asthma disease burden in a cohort of subspecialist-treated patients with SA in the United States., Methods: CHRONICLE is an observational study of adults with SA receiving biologics or maintenance systemic corticosteroids or whose disease is uncontrolled on high-dosage inhaled corticosteroids and additional controllers. Data were analyzed for patients enrolled between February 2018 and February 2021. This analysis evaluated patient-reported triggers from a 17-category survey and associations with multiple measures of disease burden., Results: Among 2793 enrolled patients, 1434 (51%) completed the trigger questionnaire. The median trigger number per patient was 8 (interquartile range, 5-10). The most frequent triggers were weather or air changes, viral infections, seasonal allergies, perennial allergies, and exercise. Patients reporting more triggers experienced more poorly controlled disease, worse quality of life, and reduced work productivity. The annualized rates of exacerbations and asthma hospitalizations increased by 7% and 17%, respectively, for each additional trigger (both P < .001). For all measures, trigger number was a stronger predictor of disease burden than blood eosinophil count., Conclusion: Among US specialist-treated patients with SA, asthma trigger number was positively and significantly associated with greater uncontrolled disease burden across multiple measures, which highlights the importance of understanding patient-reported triggers in SA., Trial Registration: ClinicalTrials.gov Identifier: NCT03373045., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Coexisting chronic rhinosinusitis and nasal polyps (CRS-NPs) substantially increases the disease burden of asthma. Dupilumab, a fully human monoclonal antibody, has established efficacy and an acceptable safety profile in asthma and CRS with NP., Objective: To evaluate long-term dupilumab efficacy in TRAVERSE (NCT02134028) patients with uncontrolled, moderate-to-severe (QUEST) or oral corticosteroid (OCS)-dependent (VENTURE) asthma with or without coexisting CRS-NP., Methods: In TRAVERSE, 317 of 1530 (21%) QUEST and 61 of 187 (48%) VENTURE patients had self-reported CRS-NP; they received subcutaneous 300 mg dupilumab every 2 weeks up to 96 weeks. Patients were categorized by parent study treatment group (placebo/dupilumab, dupilumab/dupilumab). End points included annualized asthma exacerbation rates and mean change from parent study baseline in prebronchodilator forced expiratory volume in 1 second, Asthma Control Questionnaire 5 score, Asthma Quality of Life Questionnaire score, and OCS dose., Results: Patients with coexisting CRS-NP had higher OCS dose and a history of more exacerbations. Concluding TRAVERSE, exacerbation rates decreased from 2.39 to 0.32 and 2.32 to 0.35 in dupilumab/dupilumab and 2.36 to 0.41 and 2.36 to 0.45 in placebo/dupilumab by week 96 from QUEST and VENTURE baselines, respectively. Non-CRS-NP results were similar. Improvements in forced expiratory volume in 1 second, Asthma Control Questionnaire 5 score, and Asthma Quality of Life Questionnaire score during parent studies were maintained in TRAVERSE; placebo/dupilumab patients achieved similar improvements to dupilumab/dupilumab by week 48. By week 96, 71% and 39% of OCS-dependent patients with CRS-NP and 83% and 47% without CRS-NP treated with dupilumab/dupilumab and placebo/dupilumab, respectively, stopped OCS., Conclusion: Long-term dupilumab efficacy was maintained in patients with asthma with or without self-reported coexisting CRS-NP, including OCS-sparing effects observed in OCS-dependent severe asthma., Clinical Trial Registration: ClinicalTrials.gov Identifiers: NCT02528214, NCT02414854, and NCT02134028., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the effectiveness and practicality of single maintenance and reliever therapy (SMART) in the treatment of asthma exacerbation., Data Sources: PubMed, MEDLINE, Cochrane, and Clinical Trial databases using the keywords SMART therapy, maintenance and reliever therapy, and budesonide and formoterol., Study Selections: Articles were selected based on their relevance and applicability to this topic., Results: Multiple studies have evaluated the efficacy of SMART in reducing asthma exacerbations in comparison to standard inhaled corticosteroid maintenance and short-acting beta-agonist rescue therapy. Most of the randomized trials demonstrated a reduction in asthma exacerbation with open-label studies revealing similar effectiveness in reducing asthma exacerbation. Previously, concerns have been raised regarding the administration of increased doses of long-acting beta-agonist that may potentially mask symptoms and delay appropriate medical attention. However, studies have not demonstrated an increase in morbidity or mortality. The primary concern regarding many of these trials is that they have been sponsored by pharmaceutical companies., Conclusion: Although not all studies demonstrated the effectiveness of SMART, most revealed a substantial reduction in asthma exacerbation frequency and severity., (Copyright © 2022 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

T2-low asthma is an often severe asthma subtype with limited treatment options and biologic therapeutics are lacking. Several monoclonal antibodies (mAbs) targeting non-T2 cytokines were previously reported to be ineffective in asthma. These trials often investigated heterogeneous asthma populations and negative outcomes could be related to unsuitable study cohorts. More tailored approaches in selecting participants based on specific biomarkers have been beneficial in treating severe T2-high asthma. Similarly, mAbs previously deemed ineffective bear the potential to be useful when administered to the correct target population. Here, we review individual clinical trials conducted between 2005 and 2021 and assess the suitability of the selected cohorts, whether study end points were met, and whether outcome measures were appropriate to investigate the effectiveness of the respective drug. We discuss potential target groups within the T2-low asthma population and suggest biomarkers that may predict a treatment response. Furthermore, we assess whether biomarker-guided approaches or subgroup analyses were associated with more positive study outcomes. The mAbs directed against alarmins intervene early in the inflammatory cascade and are the first mAbs found to have efficacy in T2-low asthma. Several randomized controlled trials performed predefined subgroup analyses that included T2-low asthma. Subgroup analyses were associated with positive outcomes and were able to reveal a stronger response in at least 1 subgroup. A better understanding of T2-low subgroups and specific biomarkers is necessary to identify the most responsive target population for a given mAb., (Copyright © 2022 American College of Allergy, Asthma & Immunology. All rights reserved.)

Background: Data regarding medication adherence in older adults with asthma before and during the coronavirus disease 2019 (COVID-19) pandemic are lacking., Objective: To evaluate medication adherence and determine factors associated with adherence in Medicare-enrolled older adults with asthma before and during the COVID-19 pandemic., Methods: This was a retrospective cohort analysis of Medicare-enrolled patients with asthma. Medication adherence was measured using rates of proportion of days covered for dates January to July 2019 and January to July 2020. Patients less than 65 years of age, with chronic obstructive pulmonary disease, or with cystic fibrosis were excluded. Paired t tests assessed change in adherence between 2019 and 2020. Logistic regression evaluated association of age, sex, depression, moderate or severe asthma, use of a 90-day supply, having 3 or more albuterol fills, number of medications, medication-related problems, prescribers, pharmacies, controller medication classes, and systemic corticosteroid fills with high adherence (proportion of days covered ≥ 80%)., Results: Mean adherence to asthma controller medications ranged from 75% to 90%, in 2019. Adherence significantly decreased (P < .001) from 51% to 70% for all controller medications, except theophylline in 2020. Similar results were observed among patients with moderate or severe asthma. In 2019 and 2020, number of controller medications, 3 or more albuterol fills, and having a 90-day supply were associated with high adherence (P < .001)., Conclusion: Adherence to asthma controller medications decreased considerably during the COVID-19 pandemic among Medicare-enrolled patients with asthma. Patients with markers for more severe asthma, overuse of albuterol, and a 90-day supply of controller medications were more likely to have high adherence. These findings can be used to identify opportunities to improve adherence and prescribing among adult patients with asthma., (Copyright © 2022. Published by Elsevier Inc.)

Background: Effectiveness of asthma treatment, including biologics, may be different in patients with higher body mass index (BMI)., Objective: To evaluate response to omalizumab (dosed by serum immunoglobulin E level and weight) by BMI category., Methods: Pooled data from 2 randomized, double-blind, placebo-controlled studies of adults with moderate-to-severe allergic asthma were analyzed by BMI category (<25 kg/m 2 [normal or underweight], n = 397; 25 to <30 kg/m 2 [overweight], n = 330; ≥ 30 kg/m 2 [obese], n = 268). Placebo-adjusted exacerbation rate reductions were evaluated by Poisson regression modeling. Changes from baseline in forced expiratory volume in 1 second, beclomethasone dipropionate (BDP) dose, Total Asthma Symptom Score, and Asthma Quality of Life Questionnaire were evaluated by analysis of covariance., Results: Greater placebo-adjusted exacerbation rate reductions (95% confidence interval) were observed with increasing BMI (normal or underweight, -37.4% [-69.0% to 26.8%]; overweight, -52.7% [-78.4% to 3.7%]; obese, -71.9% [-86.9% to -39.5%]). There were no differences in forced expiratory volume in 1 second improvement between BMI categories at week 16 (normal or underweight, 76.2 [5.3-147.1] mL; overweight, 98.1 [13.9-182.4] mL; obese, 69.1 [-18.9 to 157.2] mL). No differences in BDP dose reduction (µg) were noted between BMI categories (normal or underweight, 23.0 [15.7-30.3]; overweight, 22.5 [13.5-31.5]; obese, 16.6 [5.8-27.3]). Fewer patients in the higher BMI categories eliminated BDP use. There were trends for smaller improvements with higher BMI in Total Asthma Symptom Score (normal/underweight, -0.52 [-0.82 to -0.22]; overweight, -0.50 [-0.80 to -0.20]; obese, -0.39 [-0.77 to 0.00]) and Asthma Quality of Life Questionnaire (normal or underweight, 0.34 [0.16-0.52]; overweight, 0.34 [0.13-0.55]; obese, 0.15 [-0.08 to 0.39])., Conclusion: Omalizumab provides benefit to patients with moderate-to-severe allergic asthma, regardless of BMI., Trial Registration: Studies 008/009 were conducted before clinical trial registration was required, and therefore clinical trial registration numbers are not available., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To review key literature on asthma biologic therapeutics-currently available and under investigation-to inform a rational approach to select biologics for the management of people with severe asthma by precision medicine., Data Sources: We used the PubMed database to review literature on biologic therapeutics in asthma., Study Selections: We included published randomized control trials and real-world studies on biologic therapeutics, available in English, through September 2021., Results: Increased understanding of asthma endotypes and the roles of various inflammatory mechanisms has led to therapeutic agents that inhibit specific cytokines or immune pathways. Currently available biologic therapeutics target type 2-high asthma. Grouped by mechanisms of action, there are the following 3 types: (1) anti-immunoglobulin E, (2) anti-interleukin (IL)-5 or IL-5 receptor, and (3) anti-IL-4 receptor α. There are also various potential future biologic therapeutics currently under investigation. Although there remains a paucity of data regarding prospective direct head-to-head comparisons of biologic therapeutics in asthma, there are some retrospective and indirect comparison data available., Conclusion: Precision medicine guides selection of biologic therapeutics along with shared decision-making. Biomarkers, although not comprehensive, allow approximations of likely mechanisms. Use of biomarkers, to include historical levels and trends, in addition to consideration of key clinical characteristics and comorbidities can greatly help guide biologic selection. Efficacy, safety, potential adverse effects, indications for other key comorbidities, and logistics should also be considered., (Copyright © 2022 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Suboptimal adherence to inhaled corticosteroids (ICS) is associated with poor asthma control. Adult studies suggest that simplification of ICS regimen leads to better adherence., Objective: We aimed to determine whether once-daily, compared with twice-daily, ICS dosing was associated with better adherence among children with asthma., Methods: We conducted a retrospective observational study of children with asthma prescribed with either once-daily or twice-daily ICS monotherapy between 2011 and 2019. Our primary adherence outcome was the proportion of prescribed days covered (PPDC)-that is, the number of days for which the drug was dispensed by the pharmacy divided by the number of days for which it was prescribed. The impact of once-daily vs twice-daily ICS regimen on adherence was evaluated using linear multivariable regression analysis adjusting for covariates. Secondary outcomes included the proportion of patients with greater than or equal to 75% adherence analyzed using logistic regression models., Results: A total of 232 children (61% boys; mean age of 5.8 [3.6] years) were included; 120 children were prescribed once-daily, and 112 twice-daily, ICS. The median PPDC was 66.8% for the once-daily and 57.9% for the twice-daily group (P = .03). Children prescribed once-daily ICS had a 7.2% (95% confidence interval, 1.3-13.1) greater mean PPDC compared with the twice-daily group and greater odds of having PPDC greater than or equal to 75% (71.4% vs 45.5%; odds ratio, 1.80; 95% confidence interval, 1.01-3.26)., Conclusion: Our findings suggest that once-daily dosing of ICS is associated with better medication adherence than twice-daily dosing. Whether the gain in adherence leads to better asthma control and health outcomes remains to be evaluated., (Copyright © 2022 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Confirmation of effectiveness of asthma biologics in the real world is desirable because patient characteristics and experiences may differ from those included in randomized controlled trials., Objective: To evaluate real-world effectiveness of asthma biologics and identify predictors of response., Methods: We performed a retrospective study in patients with severe asthma receiving biologics. The primary outcome was change in clinically significant exacerbations at 12 months after starting biologic therapy, compared with 12 months before. Secondary outcomes were change in severe exacerbations, maintenance oral corticosteroid (OCS) dose, prebronchodilator forced expiratory volume in 1 second (FEV1), and asthma control test scores. Subgroup analyses were performed for subjects who were biologic naive or not. A stepwise logistic regression model was performed to compare responders to nonresponders., Results: A total of 112 patients were included. Biologic therapy was associated with a 59% reduction in clinically significant exacerbations (P < .001), 65% reduction in severe exacerbations (P < .001), and 54% reduction in maintenance OCS dose (P = .001) in the 12 months after starting therapy. Biologics also resulted in improvement in prebronchodilator FEV1 (P = .002) and Asthma Control Test score (P < .001). Subjects who were previously on another biologic also experienced significant improvements in exacerbation frequency, maintenance OCS dose, and asthma control. Responders were more likely to be nonsmokers and have higher baseline FEV1, gastroesophageal reflux disease, and eosinophil counts greater than 500 cells/μL., Conclusion: In a real-world setting, biologic therapy in asthma is effective in improving exacerbations, asthma control, and lung function. Patients who have a suboptimal response to 1 biologic can still benefit from treatment with a different biologic., (Copyright © 2021 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Objective: To summarize the therapeutic effects and safety of biologics either approved or in clinical development for asthma, chronic obstructive pulmonary disease, urticaria, nasal polyps, atopic dermatitis, and eosinophilic esophagitis. This review attempts to provide some guidance when choosing among agents., Data Sources: Recently published articles obtained through PubMed database searches including research articles, review articles, and case reports., Study Selections: PubMed database searches were conducted using the following keywords: biologics, asthma, COPD, urticaria, atopic dermatitis, food allergy, nasal polyps, and eosinophilic esophagitis., Results: The approval of omalizumab by the Food and Drug Administration in 2003 for patients with asthma paved the way for the development of multiple biologics for a variety of respiratory and allergic diseases. Agents approved by the Food and Drug Administration include mepolizumab, reslizumab, benralizumab, and dupilumab, and several more are in the late stages of clinical development. Owing to the overlap in the pathogenesis of respiratory and allergic diseases, many of these biologics target multiple respiratory and allergic diseases simultaneously., Conclusion: The numerous biologic options have made the selection of the best biologic for each patient a potential conundrum for clinicians. Adequate point of care biomarkers to facilitate personalized medical therapy are generally lacking. Furthermore, although clinically effective and generally safe, none of the biologics discussed in this review have induced long-standing disease remission. Nevertheless, these agents have given us the opportunity to treat the most severe patients and to better understand the biology of respiratory and allergic diseases. As knowledgeable physicians, we should embrace and be educated on these novel therapies and the pathways they target., (Copyright © 2021 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Little is known on the persistence of asthma biologic use in clinical practice., Objective: To evaluate the persistence of asthma biologic use and time to clinical response in clinical practice., Methods: A cohort of people with asthma who used at least 1 asthma biologic was constructed using data from 2003 to 2019 in the OptumLabs Data Warehouse. Treatment persistence was defined by the length of time that a person continuously used an asthma biologic, allowing for a lapse in use up to 4 months before confirming that a person stopped. Clinical response to treatment (defined as a decline in asthma exacerbations of at least 50% compared with the 6 months before starting an asthma biologic) was described over time and in relation to biologic persistence., Results: There were 9575 people who had at least 1 episode of asthma biologic use. There were 5319 people (64%, 95% confidence interval, 63%-65%) who completed 6 months or more on an asthma biologic and 3284 (45%, 95% confidence interval, 44%-46%) who completed 12 months or more. Of people with 1 or more asthma exacerbation 6 months before index biologic use, 63%, 76%, 80%, and 81% realized a 50% or more reduction in postindex asthma exacerbations in the first 6 months, 6 to 12 months, 12 to 18 months, and 18 to 24 months, respectively., Conclusion: Between 48% and 64% of people remained on an asthma biologic for 6 months or more after first use. Most people who achieved a reduction in asthma exacerbations did so in the first 6 months of treatment., (Copyright © 2021 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Patients with severe asthma (SA) have a heightened risk of exacerbations including hospitalization. The real-world, specialist-verified incidence and characteristics of exacerbations among patients with SA in the United States have not been described., Objective: To describe the real-world incidence, characteristics, and predictors of exacerbations among patients with SA in the United States., Methods: The CHRONICLE study is an ongoing observational study of specialist-treated adults with SA in the United States receiving biologic treatment or maintenance systemic corticosteroids or uncontrolled by high-dosage inhaled corticosteroids with additional controllers. For patients enrolled from February 2018 to February 2020, annualized rates and characteristics of exacerbation-related events were summarized by treatment category for 12 months before enrollment and after enrollment through the latest data collection. Results were further analyzed for subgroups of interest., Results: Among 1884 enrolled patients, 53.5% and 12.3% experienced an exacerbation and asthma hospitalization, respectively (0.81 and 0.14 per person-year). Of all exacerbations, 36%, 9%, and 15% required an unscheduled health care provider visit, emergency department visit without hospitalization, and hospitalization, respectively. Among patients not receiving biologics or systemic corticosteroids, higher blood eosinophil count, higher fractional exhaled nitric oxide, and lower total immunoglobulin E level were associated with higher exacerbation rates. Exacerbation rates decreased after starting or switching biologics (n = 1299). Multivariate analyses of enrolled patients revealed previous-year exacerbations or hospitalizations, lack of asthma control, and the geographic region also predicted event risk., Conclusion: In this real-world cohort of specialist-treated adults with SA in the United States, there was a substantial burden of exacerbations and associated health care resource utilization. Patients receiving biologics had a lower exacerbation burden., Trial Registration: ClinicalTrials.gov Identifier: NCT03373045., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Nasal polyps (NPs) are a common comorbidity of asthma. Differences in disease endotype and phenotype may have treatment implications for these concomitant conditions, including biologic therapies., Objective: To determine putative differences in type 2 biomarkers, lung function, and asthma control in patients with asthma with NPs (AwNPs) and those with asthma alone (A)., Methods: A total of 140 consecutive patients with moderate to severe asthma with or without endoscopic NPs taking a daily inhaled corticosteroid dose of greater than or equal to 800 µg and at least 1 second-line controller were identified from our National Health Service specialist respiratory and rhinology clinics. Data were collected before starting on biologics, including peripheral blood eosinophils (PBEs), fractional exhaled nitric oxide (FeNO), allergy status, spirometry, impulse oscillometry, Asthma Control Questionnaire, oral corticosteroid requiring asthma exacerbations, NP score, and Lund-Mackay score., Results: The PBE count and FeNO levels were significantly higher (P < .01), whereas specific and total immunoglobulin E levels (P < .05) were significantly lower in AwNPs vs A. In addition, FeNO had sensitivity of 81% and specificity of 67% for detecting NPs (area under the curve = 0.76; P = .001). Patients with AwNPs had less severe asthma than those with asthma without NPs (A), as reflected by fewer exacerbations (P < .001), lower inhaled corticosteroid dose (P < .001), and less impairment of impulse oscillometry (P < .05)., Conclusion: Patients with moderate to severe asthma with NPs have higher levels of PBE and FeNO despite better asthma control and lower total and specific allergy than those without NPs., (Copyright © 2021 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Objective: To identify treatment approaches that can be used in the management of patients with asthma who lack significant type 2 inflammation, also called T2 low asthma., Data Sources: Recent expert guideline updates on the management of asthma, recent journal articles and review articles, and foundational journal articles are referenced., Study Selections: This review cites clinical cohort studies of highly characterized patients with asthma, clinical interventional trials of high impact, mechanistic studies relevant to T2 low asthma, and emerging work in this area., Results: T2 low asthma accounts for approximately one-third to one-half of individuals with asthma. Characteristics of participants with T2 low asthma include higher body mass index, cigarette smoking/smoke exposure, relative lack of responsiveness to steroids, less bronchodilator reversibility, and often the presence of neutrophilic inflammation. Multiple available interventions target these characteristics, including standard inhalers, azithromycin, and lifestyle interventions of weight loss and smoking cessation., Conclusion: Treatment of T2 low asthma should involve currently available approaches and will benefit from improved definition and understanding of disease pathobiology., (Copyright © 2021 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Objective: To provide an overview of the risk factors and mechanisms underlying asthma exacerbations and the role of inhaled corticosteroids (ICSs) in preventing exacerbations., Data Sources: Queries for asthma exacerbations and ICSs were conducted using PubMed, searching for primary articles and reviews., Study Selections: Studies written in English, with a focus on well-designed randomized controlled clinical trials., Results: Asthma exacerbations remain a major source of morbidity, with future exacerbations most likely among patients with previous exacerbations and among those with peripheral blood eosinophilia. Exacerbations are often triggered by viral respiratory tract infections, but recent evidence supports nonviral triggers as well. In terms of exacerbation prevention, several approaches to ICS therapy have been found to be effective, including intermittent high-dose ICS without use of background controller in preschool children with recurrent episodic wheezing, intermittent high-dose ICS without use of background controller in adults with mild asthma, and as-needed ICS dosing whenever rescue treatment is needed among children, adolescents, and adults with mild asthma not receiving daily controller therapy., Conclusion: ICSs are highly effective in preventing exacerbations of asthma. Multiple dosing strategies have been found to reduce exacerbation risk, allowing for a personalization of approaches based on individual patient phenotypes and preferences., (Copyright © 2021 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Patients with severe asthma may remain uncontrolled despite biologic therapy in addition to standard therapy, but this disease burden has not been quantified., Objective: To estimate the clinical and economic burden in a US national sample., Methods: Patients who have severe asthma with indicated biologic treatment (earliest use = index date) were selected from the MarketScan database between January 1, 2013, and June 30, 2018. Inclusion criteria were continuous enrollment for 12 months postindex with a minimum of 2 biologic fills, greater than or equal to 12 years of age, evidence of medium- to high-dose inhaled corticosteroids and long-acting β-agonist combination before the index, and absence of other respiratory diagnoses and malignancies. Disease exacerbations (used to classify asthma control), health care costs, and treatment characteristics were reported during the 12-month postindex period., Results: The sample included 3262 biologic patients; 88% with anti-immunoglobulin E therapy (omalizumab) and 12% non-anti-immunoglobulin E (reslizumab, mepolizumab, benralizumab). The mean age was 49 (±15) years; 64% were women. Prescriptions included inhaled corticosteroids and long-acting β-agonist (82%), systemic corticosteroids (76%), and leukotriene receptor antagonists (68%). Notably, 63% of patients presented greater than or equal to 1 asthma exacerbation (mean 1.3 per patient/year). Furthermore, 35% of patients were categorized as having controlled asthma, whereas 28% were suboptimally controlled and 29% were uncontrolled. Patients with uncontrolled disease had higher all-cause and asthma-related costs ($69,206 and $45,693, respectively) than patients with suboptimally controlled ($59,407 and $40,793, respectively) or controlled disease ($53,083 and $38,393, respectively). Furthermore, 62% of newly treated patients were persistent with their index biologic., Conclusion: Biologic therapies are effective in reducing exacerbations, but a substantial proportion of patients with severe asthma treated with current biologics continue to experience uncontrolled disease, highlighting a remaining unmet need for patients with severe uncontrolled asthma., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)