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Jonathan Corren,1 David J Jackson,2,3 Thomas B Casale,4 Larry Borish,5,6 Klaus F Rabe,7,8 William W Busse,9 Jorge F Maspero,10 Daniel J Jackson,11 Nadia Daizadeh,12 Arman Altincatal,12 Amr Radwan,13 Angela Khodzhayev,13 Michel Djandji,12 Juby A Jacob-Nara,12,14 Paul J Rowe,14 Yamo Deniz13 1David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; 2King’s College London, London, UK; 3Guy’s and St Thomas’ NHS Foundation Trust, London, UK; 4Division of Allergy and Immunology, University of South Florida, Tampa, FL, USA; 5Asthma and Allergic Disease Center, University of Virginia Health System, Charlottesville, VA, USA; 6Carter Immunology Center, University of Virginia Health System, Charlottesville, VA, USA; 7LungenClinic Grosshansdorf (Member of the German Center for Lung Research [DZL]), Airway Research Center North (ARCN), Grosshansdorf, Germany; 8Christian-Albrechts University (Member of the German Center for Lung Research [DZL]), Airway Research Center North (ARCN), Kiel, Germany; 9UW Allergy, Pulmonary and Critical Care Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; 10Fundación CIDEA, Buenos Aires, Argentina; 11University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; 12Sanofi, Cambridge, MA, USA; 13Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA; 14Sanofi, Bridgewater, NJ, USACorrespondence: Jonathan Corren, David Geffen School of Medicine at UCLA, 10780 Santa Monica Blvd., Suite 280, Los Angeles, CA, 90025, USA, Email jcorren@ucla.eduPurpose: Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukins-4/-13, key and central drivers of type 2 (T2) inflammation in multiple diseases. In phase 3 QUEST (NCT02414854), dupilumab vs placebo significantly reduced asthma exacerbation rates (AER) and improved pre-bronchodilator forced expiratory volume in 1 second (FEV1) in patients with uncontrolled, moderate-to-severe asthma, with greater effects in patients with elevated T2 biomarkers (≥ 150 eosinophils/μL or fractional exhaled nitric oxide [FeNO] ≥ 25 parts per billion). Overall safety was consistent with the known dupilumab safety profile. This post hoc analysis assessed dupilumab efficacy in QUEST patients with T2 asthma with evidence of an allergic phenotype (baseline serum IgE ≥ 30 IU/mL and aeroallergen-specific IgE ≥ 0.35 IU/mL) by number of aeroallergen sensitizations: 1, 2, 3, or ≥ 4. Non-sensitized patients (serum total IgE < 30 IU/mL without evidence of allergic phenotype) were also assessed.Patients and Methods: Endpoints were annualized AER, change from baseline in pre-bronchodilator FEV1 and asthma control (5-item Asthma Control Questionnaire [ACQ-5]), and FeNO and serum total IgE levels over the 52-week treatment period.Results: In all subgroups by number of allergens sensitized, dupilumab vs placebo reduced AER by 35– 67% and improved both pre-bronchodilator FEV1 at Week 12 (least squares mean differences: 0.10– 0.26 L across subgroups) and ACQ-5 score at Week 52 (– 0.26 to – 0.43). Dupilumab significantly reduced FeNO and total IgE levels at Week 52 compared with placebo. Similar results were observed in non-sensitized patients.Conclusion: Dupilumab improved clinical outcomes and reduced biomarker levels in patients with uncontrolled, moderate-to-severe T2 asthma irrespective of allergen sensitization status or number.Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT02414854.Keywords: dupilumab, allergic asthma, type 2 asthma, perennial aeroallergen

Nicola A Hanania,1 Jorge F Maspero,2 David MG Halpin,3 David J Jackson,4,5 Reynold A Panettieri,6 Mario Castro,7 Christian Domingo,8 Nadia Daizadeh,9 Rebecca Gall,10 Juby A Jacob-Nara,11 Benjamin Ortiz,10 Michel Djandji,9 Paul J Rowe,11 Yamo Deniz10 1Section of Pulmonary and Critical Care Medicine, Baylor College of Medicine, Houston, TX, USA; 2Fundación CIDEA, Buenos Aires, Argentina; 3University of Exeter Medical School, College of Medicine and Health, University of Exeter, Exeter, UK; 4School of Immunology and Microbial Sciences, King’s College London, London, UK; 5Guy’s Severe Asthma Centre, Guy’s and St Thomas’ NHS Foundation Trust, London, UK; 6Child Health Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA; 7University of Kansas School of Medicine, Kansas City, KS, USA; 8Pulmonary Service, Corporació Sanitària Parc Taulí, Sabadell, Autonomous University of Barcelona, Barcelona, Spain; 9Sanofi, Cambridge, MA, USA; 10Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA; 11Sanofi, Bridgewater, NJ, USACorrespondence: Nicola A Hanania, Section of Pulmonary and Critical Care Medicine, Baylor College of Medicine, Houston, TX, USA, Tel +1 713 798-2400, Email hanania@bcm.edu

Alan Kaplan,1 Kenneth R Chapman,2 Syed M Anees,3 Irvin Mayers,4 Driss Rochdi,5 Michel Djandji,5 David Préfontaine,5 Andrew McIvor6 1Family Physician Airways Group of Canada, University of Toronto, Toronto, ON, Canada; 2Division of Respiratory Medicine, Department of Medicine, University of Toronto, Toronto, ON, Canada; 3Schulich School of Medicine & Dentistry – Western University, University of Windsor, ON, Canada; 4Division of Pulmonary Medicine, Department of Medicine, University of Alberta, Edmonton, AB, Canada; 5Novartis Pharmaceuticals Canada Inc., Montreal, QC, Canada; 6Department of Medicine, McMaster University, Firestone Institute for Respiratory Health, Hamilton, ON, Canada Purpose: In contrast to randomized controlled trials (RCTs), changes in maintenance pharmacotherapy in clinical practice occur without a washout period. The Prospective cohort study for the real-life effectiveness evaluation of glycOpyrronium With indacatERol combination in the management of COPD in Canada (POWER) study evaluated the real-life effectiveness of indacaterol/glycopyrronium (IND/GLY) following a direct switch from a long-acting muscarinic antagonist (LAMA, tiotropium) or long-acting β2-agonist (LABA)/inhaled corticosteroid (ICS) maintenance treatment (salmeterol/fluticasone [SFC]).Methods: POWER was a single-cohort, prospective, multicenter, interventional study in which patients with moderate-to-severe COPD, who remained symptomatic on their current treatment of once-daily (od) tiotropium 18 µg or twice-daily (bid) SFC (any dose), were switched to treatment with open-label IND/GLY 110/50 µg od for 16 weeks. Effectiveness end points were change from baseline in trough FEV1, transition dyspnea index (TDI) total scores, and COPD assessment test (CAT) scores at 16 weeks.Results: Trough FEV1 improved by 175 mL at Week 16 in patients who switched to IND/GLY. The change was 176 mL (95% CI: 135–217) when switched from tiotropium and 172 mL (95% CI: 85–258) when switched from SFC fixed-dose combination (FDC). At Week 16, significant improvements were observed in the mean TDI total scores (Δ=2.5) and CAT scores (Δ=-6.5) after the switch to IND/GLY treatment (both P

Background: Accumulating data implicate interleukin (IL)-33, a proinflammatory cytokine released locally upon epithelial cell damage, in the pathogenesis of COPD. In a phase 2 study, itepekimab, a human monoclonal antibody against IL-33, reduced exacerbations and improved lung function in a subgroup analysis of former smokers with COPD with an acceptable safety profile., Methods: The study designs of AERIFY-1 and AERIFY-2 are described in this article., Discussion: The primary objective of AERIFY-1/2 (NCT04701983/NCT04751487), two phase 3 randomised, double-blind, placebo-controlled trials, is to assess the efficacy and safety of itepekimab versus placebo in a population of former smokers with moderate-to-severe COPD over up to 52 weeks. An additional secondary population of current smokers are being enrolled in AERIFY-2. These two studies will enrol patients (aged 40-85 years) with COPD and chronic bronchitis who had ≥2 moderate or ≥ 1 severe exacerbations within the previous year despite standard-of-care triple or double background therapy. All participants are required to have ≥10-pack-year smoking history, and ≥6 months since smoking cessation for former smokers. The primary end-point is the annualised rate of moderate or severe acute exacerbation of COPD. Secondary end-points include change from baseline in pre- and post-bronchodilator forced expiratory volume in 1 s, and annualised frequency of severe exacerbations. Symptomatic end-points include Evaluating Respiratory Symptoms in COPD and St. George's Respiratory Questionnaire, safety and anti-drug antibody responses., Competing Interests: Conflict of interest: K.F. Rabe reports consultancy, speaker fees’ and advisory board membership for AstraZeneca, Boehringer Ingelheim, Chiesi, Gilead, GSK, Novartis, Pearl, Sanof and Teva; and is cofounder of rnatics, Germany. Conflict of interest: F.J. Martinez has been on steering committees for Afferent/Merck, AstraZeneca, Bayer, Boehringer Ingelheim, Gilead, GlaxoSmithKline, Nitto Pharma, Patara Pharma/Respivant Sciences, Pearl Pharmaceuticals, ProMedior/Roche, ProMetic Life Sciences, Stromedix/Biogen and Veracyte; has been an advisory board member for AstraZeneca, BioScale/ProTerrix Bio, Boehringer Ingelheim, Chiesi, CSL Behring, Gala Therapeutics, Genentech, GlaxoSmithKline, Novartis, Pearl Pharmaceuticals, Physicians Education Resource, Sunovion, Teva and Zambon; has been a consultant for Bridge Biotherapeutics, Bristol Myers Squibb and twoXR; reports continuing medical education presentation support from the Canadian Respiratory Network, Chiesi, CME Outfitters, Dartmouth University, France Foundation, Inova Fairfax, MD Magazine, Methodist Hospital, Miller Communications, National Association for Continuing Education/Haymarket, New York University, PeerView, Prime Education, Rare Diseases Healthcare Communication, Rockpointe, University of Alabama at Birmingham, UpToDate, Vindico Pharmaceuticals, WebMD/MedScape and Zambon; and has been on the data and safety monitoring board for Boehringer Ingelheim and GlaxoSmithKline. Conflict of interest: S.P. Bhatt has served on advisory boards for Boehringer Ingelheim and Regeneron, received consulting fees from Sanofi, and reports fees for continuing medical education from IntegrityCE. Conflict of interest: T. Kawayama reports support from GSK, AstraZeneca, Novartis Pharma and Healios. Conflict of interest: B.G. Cosio has served as a consultant and received speaker fees from AstraZeneca, Boehringer Ingelheim, Novartis, Chiesi, Menarini, GSK, Sanofi and Teva. Conflict of interest: R.M. Mroz reports support from AstraZeneca, Boehringer Ingelheim, Chiesi, Genentech, MSD, Gilead, GSK, Novartis, Pearl Pharmaceuticals, Sanofi and Teva. Conflict of interest: M.M. Boomsma, H. Goulaouic, M. Djandji, Y. Liu, C.R. Xu and H. Staudinger are Sanofi employees and may hold stock and/or stock options in the company. Conflict of interest: M.C. Nivens, X. Soler, M.P. Kosloski and D.J. Lederer are Regeneron Pharmaceuticals Inc. employees and shareholders. Conflict of interest: N. Amin is a prior employee and shareholder for Regeneron Pharmaceuticals Inc. Conflict of interest: R.M. Abdulai is a prior employee and stock holder for Sanofi., (Copyright ©The authors 2024.)

Objective: The open-label extension TRAVERSE study (NCT02134028) assessed dupilumab long-term safety and efficacy in patients who completed Phase 2/3 dupilumab asthma studies. This post hoc analysis evaluated long-term efficacy in type 2 patients with and without evidence of allergic asthma who enrolled in TRAVERSE from Phase 3 QUEST (NCT02414854) and Phase 2b (NCT01854047) studies. Non-type 2 patients with evidence of allergic asthma were also assessed., Methods: Unadjusted annualized exacerbation rates during parent study and TRAVERSE treatment period, and changes from parent study baseline in pre-bronchodilator forced expiratory volume in 1 s (FEV 1 ) and in 5-item Asthma Control Questionnaire (ACQ-5) scores were assessed in patients from QUEST and Phase 2b; change from parent study baseline in total IgE level was assessed in patients enrolled from Phase 2b., Results: 2062 patients from Phase 2b and QUEST enrolled in TRAVERSE. Of these, 969 were type 2 with evidence of allergic asthma; 710 were type 2 without evidence of allergic asthma; and 194 were non-type 2 with evidence of allergic asthma at parent study baseline. In these populations, reductions in exacerbation rates observed during parent studies were sustained during TRAVERSE. Type 2 patients who switched from placebo arm to dupilumab in TRAVERSE experienced similar reductions in severe exacerbation rates, and improvements in lung function and asthma control to those patients who already received dupilumab during the parent study., Conclusion: Dupilumab efficacy was sustained for up to 3 years in patients with uncontrolled, moderate-to-severe type 2 inflammatory asthma, with or without evidence of allergic asthma.ClinicalTrials.gov identifier: NCT02134028.

Background: Cytokines, such as interleukins (IL)-4/5/13, play a key role in multiple type 2 inflammatory diseases, including allergic asthma. Dupilumab, a human monoclonal antibody, blocks the shared receptor component for IL-4/IL-13, inhibiting signaling. In this post hoc analysis of VOYAGE (NCT02948959), dupilumab efficacy was evaluated in patients aged 6-11 years with type 2 asthma with or without evidence of allergic asthma (baseline serum total IgE ≥30 IU/mL and ≥1 perennial aeroallergen-specific IgE ≥0.35kU/L)., Methods: Annualized severe exacerbation rates (AER) and changes in pre-bronchodilator (Pre-BD) forced expiratory volume in one second (FEV 1 ), percent-predicted pre-BD FEV 1 (ppFEV 1 ), and Asthma Control Score (ACQ)-7 were assessed during the treatment period., Results: 350 children (261 with and 89 without evidence of allergic asthma) were included. Dupilumab versus placebo significantly reduced AER in patients with (0.24 vs. 0.62, relative risk reduction [RRR]: 62% [95% CI, 39-76], P < .0001) and without (0.39 vs. 0.80, RRR: 51% [95% CI, 0-76], P < .05) evidence of allergic asthma. Significant improvements in ppFEV 1 , pre-bronchodilator FEV 1 , and ACQ-7 scores were observed in dupilumab versus placebo throughout the treatment period in patients with evidence of allergic asthma. In patients without evidence of allergic asthma, numerical improvements in pre-bronchodilator FEV 1 and asthma control were observed by Week 52., Conclusion: Dupilumab versus placebo reduced asthma exacerbations in children with type 2 asthma irrespective of evidence of allergic asthma; similar trends were observed in changes in lung function. Significant improvement in asthma control was observed in patients with evidence of allergic asthma, but not in those without., (© 2023 Sanofi and The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Objective: While advances in asthma care have been made in Latin America, there is still a large unmet need in patients with uncontrolled asthma. This post hoc analysis of the QUEST study assessed safety and efficacy of dupilumab in the subgroup of patients enrolled in Latin American countries with a type 2 inflammatory asthma phenotype (blood eosinophils ≥ 150cells/µL or FeNO ≥25ppb)., Methods: LIBERTY ASTHMA QUEST (NCT02414854) was a phase 3, multinational, randomized, double-blind, placebo-controlled study in patients with uncontrolled, moderate-to-severe asthma. Eligible patients ≥ 12 years of age were randomized in a 2:2:1:1 ratio to receive 52 weeks of add-on subcutaneous dupilumab 200 or 300 mg every 2 weeks or matched-volume placebos. Pre-specified co-primary efficacy endpoints were the annualized rate of severe exacerbations during the treatment period and the change from baseline in pre-bronchodilator FEV 1 at treatment week 12. Asthma control, changes in asthma biomarker levels, and dupilumab safety were also evaluated., Results: 530 (27.9% of the overall QUEST population; dupilumab: 353, placebo: 177) Latin-American patients were recruited; 420 (79.2%) had a type 2 inflammatory asthma phenotype. Dupilumab vs placebo reduced the annualized rate of severe exacerbations by 52.7% ( P  < 0.001) and increased pre-bronchodilator FEV 1 at week 12 by 0.15 L ( P  < 0.001), in the type 2 population. Safety was consistent with the known dupilumab safety profile., Conclusions: Consistent with the results in the overall population, dupilumab reduced the risk of severe asthma exacerbations and improved lung function in Latin American patients with uncontrolled, moderate-to-severe asthma and a type 2 phenotype.

Background: FeNO may have a role as both a prognostic and predictive biomarker in combination with eosinophils for assessing responsiveness to some biological therapies., Objective: We evaluated the value of baseline FeNO, adjusted for baseline blood eosinophil levels and other clinical characteristics, as an independent predictor of treatment response to dupilumab in patients with uncontrolled moderate-to-severe asthma., Methods: We performed a post hoc analysis of LIBERTY ASTHMA QUEST (NCT02414854), a phase 3, double-blind study in patients aged 12 years and older with uncontrolled moderate-to-severe asthma, who received dupilumab 200 or 300 mg, or placebo every 2 weeks up to 52 weeks. We assessed the annualized event rate of severe exacerbations and least-squares mean change from baseline in prebronchodilator FEV 1 at weeks 12 and 52 in relationship to baseline FeNO, adjusted for eosinophils and other clinical characteristics., Results: The annualized event rate increased with increasing baseline FeNO in placebo and decreased in dupilumab groups. The relative risk of severe exacerbations was 22·7%, 58·3%, and 69·3% lower for dupilumab versus placebo for the FeNO less than 25, 25 to less than 50, and 50 and greater parts per billion subgroups. The magnitude of FEV 1 improvement increased with higher baseline FeNO for dupilumab and was consistent across the continuum of FeNO levels in placebo. Both findings were independent of blood eosinophil levels. Significant differences were observed between FeNO subgroups., Conclusions: Increased baseline FeNO was associated with greater clinical effects in dupilumab versus placebo independently of eosinophil levels and other clinical characteristics., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Type 2 cytokines IL-4/IL-5/IL-13 play an important role in pathogenesis of type 2 conditions, including asthma. Dupilumab, a human monoclonal antibody, blocks the shared receptor component for IL-4/IL-13, inhibiting signaling. In phase 2b (P2B) (NCT01854047) and phase 3 VENTURE (NCT02528214), dupilumab reduced annualized severe exacerbation rates (AER), improved forced expiratory volume in 1 second (FEV 1 ), and was generally well tolerated in patients with uncontrolled, moderate-to-severe, or oral corticosteroid (OCS)-dependent severe asthma., Objective: The post hoc assessment of dupilumab efficacy versus placebo in P2B and VENTURE in patients stratified by allergic status., Methods: Allergic asthma was defined as total serum IgE ≥30 IU/mL and ≥1 perennial aeroallergen-specific IgE ≥0.35 kU/L at baseline. AER, prebronchodilator (BD) FEV 1 , FEV 1 /forced vital capacity (FVC) ratio, asthma control (5-item Asthma Control Questionnaire), health-related quality of life (HRQoL; Asthma Quality of Life Questionnaire), type 2 biomarkers, specific IgE, and OCS reduction (VENTURE only) were assessed., Results: In patients with allergic asthma, dupilumab (P2B: pooled 200/300 mg; VENTURE: 300 mg) every 2 weeks versus placebo reduced AER (P2B: -60%, P < .01; VENTURE: -72%, P < .001), and, in P2B, increased pre-BD FEV 1 (P < .01) and FEV 1 /FVC (P < .05). In both studies, dupilumab significantly improved asthma control and HRQoL and reduced most type 2 biomarkers. Dupilumab significantly reduced OCS use in VENTURE. Similar benefits were observed in patients without evidence of allergic asthma., Conclusions: Dupilumab significantly reduced AER and improved lung function, asthma control, and HRQoL in patients with or without evidence of allergic asthma., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Safety and efficacy data for dupilumab beyond 1 year are lacking for patients from Japan with moderate-to-severe asthma., Methods: The TRAVERSE open-label extension (OLE) study (NCT02134028) assessed the safety and efficacy of dupilumab 300 mg every 2 weeks up to 96 weeks in 2282 patients who completed a previous dupilumab asthma study. The primary endpoint was incidence of treatment-emergent adverse events (TEAEs). Secondary endpoints included annualized severe exacerbation rate and change from parent study baseline in pre-bronchodilator forced expiratory volume in 1 second (FEV 1 ), asthma control, quality of life, and blood eosinophil levels. Anti-drug antibodies (ADA) were evaluated. We report results in 160 (7.8% of exposed population) patients recruited from Japanese centers with non-oral corticosteroid (OCS)-dependent asthma rolled over from two parent studies, and in subgroups with a type 2 inflammatory phenotype., Results: TEAEs were consistent with the parent studies and the known safety profile of dupilumab. One patient permanently discontinued treatment due to TEAEs. Exacerbation rates remained low and were sustained to Week 96, as were improvements in pre-bronchodilator FEV 1 . Rapid, sustained improvements were observed in dupilumab-treated patients who previously received placebo in a parent study, while further improvements in exacerbation rates, asthma control, and asthma-related quality of life were observed in those continuing dupilumab. Blood eosinophil levels decreased progressively while on treatment. Treatment-emergent ADA responses were highest in patients who had previously received placebo. Efficacy results were consistent in patients with a type 2 phenotype., Conclusions: Long-term dupilumab treatment was well tolerated and efficacious in patients with non-OCS-dependent, moderate-to-severe asthma recruited from Japan. (Funded by Sanofi and Regeneron Pharmaceuticals, Inc.; ClinicalTrials.gov identifier, NCT02134028)., (Copyright © 2022 Japanese Society of Allergology. Published by Elsevier B.V. All rights reserved.)

Background and Objective: Dupilumab blocks the shared receptor component for interleukin (IL)-4/IL-13, key and central drivers of type 2 inflammation in multiple diseases. In phase 3 QUEST (NCT02414854), add-on dupilumab 200 and 300 mg every 2 weeks reduced severe exacerbations, improved pre-bronchodilator forced expiratory volume in 1 s (FEV 1 ), and was generally well tolerated in patients with uncontrolled moderate-to-severe asthma. This post hoc analysis assessed dupilumab efficacy in subpopulations of patients with type 2 asthma and high-dose inhaled corticosteroids (ICS)., Methods: Adjusted annualized severe exacerbation rates over the treatment period, least squares (LS) mean change from baseline at Week 12 in pre-bronchodilator FEV 1 , and LS mean change from baseline at Week 24 in 5-item Asthma Control Questionnaire (ACQ-5) scores were analyzed in subgroups of patients receiving high-dose (>500 μg) ICS with baseline blood eosinophils ≥150 cells/μL and/or fractional exhaled nitric oxide ≥25 ppb. Subgroups included allergic phenotype (with/without), comorbid chronic rhinosinusitis and/or nasal polyposis (with/without), pre-bronchodilator FEV 1 /forced vital capacity (<70%/≥70%), blood eosinophil level, exacerbation history, median baseline pre-bronchodilator FEV 1 , age at asthma onset (≤40/>40 years), median FEV 1 reversibility, body mass index (<30/≥30 kg/m 2 ), and sex., Results: Dupilumab vs placebo reduced exacerbations and improved pre-bronchodilator FEV 1 at Week 12 and ACQ-5 at Week 24 across subgroups of patients with type 2 asthma and high-dose ICS at baseline. Dupilumab was also effective in patients receiving medium-dose ICS., Conclusion: Dupilumab reduced severe exacerbations and improved lung function and asthma control in subgroups of patients with type 2 asthma and high-dose ICS at baseline., Clinical Trial Registration Number: NCT02414854., Competing Interests: Declaration of competing interest Bourdin A: GSK – non-financial support during the conduct of the study; Acceleron Pharma, Actelion, Galapagos, Merck Sharp & Dohme, Nuvaira, Pulmonx, United Therapeutics, Vertex Pharmaceuticals – other; Boehringer Ingelheim – grants, personal fees; AstraZeneca, Chiesi, GSK, Regeneron Pharmaceuticals, Inc., Sanofi – personal fees. Virchow JC: Altana, AstraZeneca, Avontec, Bayer, Bencard Allergie, Bionorica, Boehringer Ingelheim, Chiesi, Essex Pharma Development, GSK, Hexal, Janssen-Cilag, Leti, Meda Pharmaceuticals, Merck, MSD, Mundipharma, Novartis, Nycomed, Pfizer, Revotar Biopharmaceuticals, Sandoz, Stallergenes Greer, Schwarz Pharma, Teva, UCB, Zydus Cadila – honoraria. Avontec, Boehringer Ingelheim, Chiesi, Essex Pharma Development, GSK, Hexal, Janssen-Cilag, Meda Pharmaceuticals, MSD, Mundipharma, Novartis, Regeneron Pharmaceuticals, Inc., Revotar Biopharmaceuticals, Roche, sanofi-aventis, Sandoz, Schwarz Pharma, Teva, UCB – advisory board participant. Deutsche Forschungsgesellschaft, GSK, Land Mecklenburg-Vorpommern, MSD – research grants. Papi A: AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Mundipharma, Teva – report grants, personal fees, nonfinancial support, other; Menarini, Novartis, Zambon – personal fees, nonfinancial support; Sanofi – grants (all outside the submitted work). Lugogo NL: Amgen, AstraZeneca, Avillion, Genentech, Gossamer Bio, GSK, Regeneron Pharmaceuticals, Inc., Sanofi, Teva − research support paid to institution; Amgen, AstraZeneca, Genentech, GSK, Novartis, Regeneron Pharmaceuticals, Inc., Sanofi, Teva − advisory board member, consultant; AstraZeneca – travel support; AstraZeneca, GSK – honoraria for non-speaker's bureau presentations. Bardin P: AstraZeneca, Boehringer Ingelheim, GSK, Novartis, Sanofi – consultant, speaker fees. Antila M: AbbVie, Angion Biomedica Corp, AstraZeneca, BeiGene, EMS, Eurofarma, GSK, Humanigen, Janssen, Novartis, Sanofi – clinical trial funding; Aché, AstraZeneca, Chiesi, Eurofarma, IPI ASAC Brasil, Sanofi – honoraria; AstraZeneca, GSK, Novartis, Sanofi – meeting or travel support; Abbott, AstraZeneca, Chiesi, Sanofi, Zambon – data safety monitoring board and/or advisory board member. Halpin DMG: AstraZeneca, Boehringer Ingelheim, Chiesi, CSL Behring, GSK, Novartis, Pfizer, Sandoz, Sanofi – advisory board member, speaker fees. Daizadeh N: Sanofi – former employee, may hold stock and/or stock options in the company. Djandji M, Jacob-Nara JA, Rowe PJ: Sanofi − employees, may hold stock and/or stock options in the company. Ortiz B: Regeneron – former employee, may hold stock and/or stock options in the company. Gall R, Deniz Y: Regeneron Pharmaceuticals, Inc. – employees and shareholders., (Copyright © 2022. Published by Elsevier Ltd.)

Background: Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin-4/-13, key and central drivers of type 2 inflammation in multiple diseases. In the phase 3 LIBERTY ASTHMA VENTURE (VENTURE) study (NCT02528214), dupilumab versus placebo reduced oral corticosteroid (OCS) dose and improved clinical outcomes in patients with OCS-dependent severe asthma. Dupilumab efficacy in patients with varying disease burden (defined by baseline OCS dose) has not been assessed., Objective: This post hoc analysis of VENTURE evaluated dupilumab efficacy across subgroups defined by baseline OCS dose., Methods: The OCS dose, proportion no longer needing OCS at week 24, annualized severe exacerbation rate, and least squares mean change from baseline in pre- and post-bronchodilator forced expiratory volume in 1 second at week 24 were evaluated in VENTURE patients with OCS-dependent severe asthma receiving dupilumab 300 mg every 2 weeks versus placebo, categorized by a baseline OCS dose of less than 10 mg/d or 10 or more mg/d., Results: Dupilumab reduced daily OCS dose from baseline at week 24 in both dose groups. In dupilumab-/placebo-treated patients with a baseline OCS dose of less than 10 mg/d and 10 or more mg/d, 72%/42% and 37%/23% stopped OCS by week 24 (P < .01/P < .05), respectively. Dupilumab significantly reduced the annualized severe exacerbation rate by 71% and 48% (P < .01/P < .05). At week 24, dupilumab improved pre- and post-bronchodilator forced expiratory volume in 1 second in patients in both dose groups., Conclusions: In patients with OCS-dependent severe asthma receiving lower or higher baseline OCS doses, dupilumab significantly reduced the OCS dose and improved the likelihood of no longer requiring OCS while also reducing exacerbations and improving lung function., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Type 2 inflammatory diseases often coexist in patients. Dupilumab targets type 2 inflammation and has demonstrated treatment benefits in patients with atopic dermatitis (AD), asthma, and chronic rhinosinusitis with nasal polyps (CRSwNP) with an acceptable safety profile., Objective: This post hoc analysis across five phase 3 studies in patients with moderate to severe AD or asthma, or severe CRSwNP, evaluated time of onset and duration of the treatment response., Methods: Patients received subcutaneous dupilumab 200/300 mg or placebo. Assessments included the Eczema Area and Severity Index, Peak Pruritus Numerical Rating Scale, and Dermatology Life Quality Index in AD; pre-bronchodilator FEV 1 , daily morning peak expiratory flow, and symptom scores in asthma; and University of Pennsylvania Smell Identification Test, daily nasal congestion, and loss of smell scores in CRSwNP., Results: At week 2 after the initiation of dupilumab versus placebo, 67.8% versus 36.5% of AD patients achieved a clinically meaningful benefit (Eczema Area and Severity Index: 50% or greater improvement; Peak Pruritus Numerical Rating Scale: 3 point or greater improvement; or Dermatology Life Quality Index: 4 point or greater improvement) (P < .001). Moreover, 61.6% versus 39.9% of asthma patients achieved improvements in pre-bronchodilator FEV 1 of 100 mL or greater and 48.8% versus 26.3% achieved 200 mL or greater improvement (both P < .001); 33.2% versus 5.6% of CRSwNP patients regained a sense of smell (P < .001). Treatment effects further improved or were sustained to the end of treatment., Conclusions: Clinically meaningful responses were achieved rapidly after the first dupilumab dose in AD, asthma, or CRSwNP and were sustained throughout treatment (see Video in this article's Online Repository at www.jaci-inpractice.org)., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The phase 3 LIBERTY ASTHMA QUEST study (ClinicalTrials.gov: NCT02414854) in patients with uncontrolled, moderate-to-severe asthma has demonstrated the efficacy and safety of dupilumab 200 and 300 mg every 2 weeks versus placebo. This post hoc analysis assessed the effect of dupilumab on efficacy outcomes and asthma control across a range of historical exacerbation rates in patients with type 2-high asthma., Methods: Annualised severe exacerbation rates over the 52-week treatment period, pre-bronchodilator forced expiratory volume in 1 s (FEV 1 ) at weeks 12 and 52, and the five-item Asthma Control Questionnaire (ACQ-5) score at weeks 24 and 52 were assessed in patients with ≥1, ≥2 or ≥3 exacerbations in the previous year. Subgroups were stratified by baseline blood eosinophils ≥150 or ≥300 cells·μL -1 or baseline exhaled nitric oxide fraction ≥25 ppb and baseline inhaled corticosteroid (ICS) dose., Results: Across all type 2-high subgroups, dupilumab versus placebo significantly reduced severe exacerbations by 54-90%, with greater improvements in patients with more exacerbations prior to study initiation. Similarly, improvements in FEV 1 (least squares (LS) mean difference versus placebo: ≥1 exacerbations, 0.15-0.25 L; ≥2 exacerbations, 0.12-0.32 L; ≥3 exacerbations, 0.09-0.38 L; majority p<0.05) and ACQ-5 score (LS mean difference range: ≥1 exacerbations, -0.30 to -0.57; ≥2 exacerbations, -0.29 to -0.56; ≥3 exacerbations, -0.43 to -0.61; all p<0.05) were observed, irrespective of prior exacerbation history, across all subgroups., Conclusions: Dupilumab significantly reduced severe exacerbations and improved FEV 1 and asthma control in patients with elevated type 2 biomarkers irrespective of exacerbation history and baseline ICS dose., Competing Interests: Conflict of interest: J. Corren reports nonfinancial support for research from Sanofi, outside the submitted work. Conflict of interest: C.H. Katelaris reports nonfinancial support (advisory board member and principal study investigator) from Sanofi, outside the submitted work. Conflict of interest: M. Castro reports nonfinancial support for research from the American Lung Association, Gossamer, NIH, PCORI and Shionogi, personal fees for lectures and nonfinancial support for research from AstraZeneca, personal fees for lectures and consultancy, and nonfinancial support for research from Boehringer Ingelheim and Sanofi, personal fees for consultancy and nonfinancial support for research from Novartis, personal fees for consultancy from Boston Scientific and Vida Pharma, personal fees for lectures and consultancy from Teva, personal fees for lectures from Genentech and Regeneron Pharmaceuticals, Inc., personal fees (royalties) from Elsevier, outside the submitted work. Conflict of interest: J.F. Maspero reports being a speaker for AstraZeneca, GlaxoSmithKline, Menarini, Novartis, Sanofi, Teva and Uriach; and has received research grants from Novartis, outside the submitted work. Conflict of interest: L.B. Ford reports nonfinancial support for research from AstraZeneca, DBV, Genentech, Gossamer, Novartis and Teva, personal fees for consultancy from Sanofi, outside the submitted work. Conflict of interest: D.M.G. Halpin reports personal fees for lectures and advisory board work from AstraZeneca, Boehringer Ingelheim, Chiesi, CSL Behring, GlaxoSmithKline, Novartis, Pfizer, Sandoz and Sanofi, outside the submitted work. Conflict of interest: M.S. Rice is an employee of Sanofi and may hold stock and/or stock options in the company. Conflict of interest: A. Radwan is an employee and shareholder of Regeneron Pharmaceuticals, Inc. Conflict of interest: Y. Deniz is an employee and shareholder of Regeneron Pharmaceuticals, Inc. Conflict of interest: P.J. Rowe is an employee of Sanofi and may hold stock and/or stock options in the company. Conflict of interest: A. Teper is a former employee of Sanofi. Conflict of interest: M. Djandji is an employee of Sanofi and may hold stock and/or stock options in the company., (Copyright ©The authors 2021.)

Background: Dupilumab blocks the shared receptor component for interleukin (IL)-4/IL-13, key drivers of type 2 inflammation. In phase 2b (NCT01854047) and phase 3 LIBERTY ASTHMA QUEST (NCT02414854), add-on dupilumab 200/300 mg every 2 weeks (q2w) reduced severe exacerbations, improved prebronchodilator (pre-BD) forced expiratory volume in 1 second (FEV 1 ) and quality of life measures, and it was generally well tolerated in patients with uncontrolled, persistent (phase 2b), or moderate-to-severe (phase 3) asthma., Methods: In patients on high-dose inhaled corticosteroids (ICS) with type 2-high asthma (subgroups including baseline blood eosinophils ≥150/300 cells/µL and/or fractional exhaled nitric oxide [FeNO] ≥25 ppb), annualized severe exacerbation rates over the treatment period, changes from baseline in pre-BD FEV 1 and asthma control (5-item asthma control questionnaire [ACQ-5]) were analyzed., Results: In high-dose ICS type 2-high subgroups, dupilumab 200/300 mg q2w vs placebo in the phase 2b (24 weeks) and phase 3 (52 weeks) studies significantly reduced severe exacerbations by 55%-69%/57%-60% (all P<.05) and 53%-69%/48%-66% (all P < .001), respectively, except in patients with ≥ 300 eosinophils/µL in phase 2b study (24%/50% (P = .52/0.15). Across subgroups, pre-BD FEV 1 improved by 0.18-0.22 L/0.19-0.24 L (all P < .05) and 0.23-0.36 L/0.15-0.25 L (all P < .01) and ACQ-5 scores were reduced by 0.46-0.55/0.47-0.85 (all P < .05) and 0.38-0.50/0.24-0.30 (all P < .05), respectively, except dupilumab 200 mg q2w in phase 2b in patients with FeNO ≥ 25 ppb (0.41; P = .09). Dupilumab was also effective in patients taking medium-dose ICS., Conclusion: Dupilumab significantly reduced severe exacerbations and improved lung function and asthma control in patients with type 2-high asthma on high-dose ICS at baseline., (© 2020 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Asthma is the most common chronic disease of childhood and a leading cause of childhood morbidity. The aim of the current study was to assess the effectiveness of montelukast administered as monotherapy or in combination with current inhaled corticosteroids (ICS) in pediatric patients with uncontrolled asthma as per the Canadian Asthma Consensus Guidelines., Methods: Twelve-week, multicentre, open-label, observational study. Primary effectiveness outcome was the proportion of patients achieving asthma control (Asthma Control Questionnaire (ACQ) score ≤0.75) at weeks 4 and 12., Results: A total of 328 patients with uncontrolled asthma (ACQ > 0.75) were enrolled with mean ± SD age of 6.9 ± 3.4 years. Among these, 76 (23.2%) were treated with montelukast monotherapy and 252 (76.8%) with montelukast combined with ICS. By 4 weeks of treatment 61.3% and 52.9% of the patients in the monotherapy and combination group, respectively, achieved asthma control. These proportions increased to 75.0% and 70.9%, respectively, at 12 weeks. Within the monotherapy group, clinically significant improvements in the ACQ score (mean ± SD of 1.67 ± 0.69, 0.71 ± 0.70 and 0.50 ± 0.52 at baseline, 4 and 12 weeks, respectively; p < 0.001) and the PACQLQ score (mean ± SD of 5.34 ± 1.14, 6.32 ± 0.89 and 6.51 ± 0.85 at baseline, 4 and 12 weeks, respectively; p < 0.001) were observed. In the combination group, the mean ± SD ACQ score significantly improved from 2.02 ± 0.83 at baseline to 0.90 ± 0.86 at 4 weeks and 0.64 ± 0.86 at 12 weeks (p < 0.001), while the PACQLQ score improved from 4.42 ± 1.35 at baseline to 5.76 ± 1.30 at 4 weeks and 6.21 ± 1.03 at 12 weeks (p < 0.001). After a 12-week montelukast add-on therapy, 22.6% of patients reduced their ICS dosage. Similar results were observed among preschool- and school-aged patients., Conclusions: Montelukast as monotherapy or in combination with ICS represents an effective treatment strategy for achieving asthma control in pediatric patients and improving caregivers' quality of life., Trial Registration: This study is registered at ClinicalTrial.gov: NCT00832455.

Objective: To evaluate the effectiveness of montelukast as add-on therapy for patients diagnosed with asthma and concurrent allergic rhinitis who remain uncontrolled while receiving inhaled corticosteroid (ICS) monotherapy or ICS/long-acting beta-2-agonist (LABA) therapy in a community practice setting., Design: An eight-week, multicentre, open-label, observational study. Patients were 15 years of age or older and, while treated with an ICS or ICS/LABA, had allergic rhinitis and uncontrolled asthma symptoms by at least two criteria as per the Canadian Asthma Consensus Guidelines. The primary outcome measure was the percentage of patients with controlled asthma symptoms after eight weeks of treatment with montelukast 10 mg once daily added to ICS or ICS/LABA therapy., Results: In total, 1004 patients participated in the survey phase of the study. Of these patients, 319 continued in the treatment phase and 301 (94.4%) completed the eight-week assessment. At baseline, all patients had uncontrolled asthma symptoms based on the Canadian Asthma Consensus Guidelines; at the eight-week assessment, 229 patients (76.1%) achieved asthma control. According to the Asthma Control Questionnaire (as determined by scores of 0.75 or less), 164 patients (54.7%) achieved well-controlled asthma at week 8. The mean (+/- SD) Asthma Control Questionnaire score decreased from 2.03+/-0.80 to 0.92+/-0.80 (P<0.001) for all patients, representing a clinically significant improvement. A statistically and clinically significant reduction in the overall Mini Rhinitis Quality of Life Questionnaire score was achieved with a decrease from 2.57+/-1.20 to 1.12+/-1.00 (-1.45+/-1.35; P<0.001). Patient and physician satisfaction rates with montelukast add-on therapy were also significantly increased when compared with baseline treatment., Conclusion: Montelukast add-on therapy is effective for managing asthma and allergic rhinitis symptoms in patients who were previously uncontrolled with ICS or ICS/LABA treatment.