Clinical phenotyping improves choices of biologics in asthma - Authors' reply.

# Clinical phenotyping improves choices of biologics in asthma – Authors’ reply *The Lancet 2026* Correspondence University of Graz, Graz 8036, Austria (KM); Moreover, the apparent treatment and GSK for the NIH PrecISE Study; has received study Department of Medicine V, Comprehensive effect in such uncontrolled data drugs from Sanofi-Regeneron for the NIH IDEA Study; Pneumology Center, University Hospital, LMU has received grants from Amgen, Genentech, and GSK could be inflated by the absence Munich, Member of the German Center of Lung for the NIH SARP4 Study; and has received study Research, Munich, Germany (KM); Clinic for of a blinded comparator. Placebo drugs and a grant for the NIH-funded study PARK Pneumology, Allergology and Intensive Care responses in severe asthma—eg, as from Genentech. DJJ has received consulting fees and Medicine, Department of Internal Medicine, speaker fees, and research grants to his institution, seen in oral corticosteroid-sparing University of Rostock, Rostock, Germany (JCV, ML) from AstraZeneca and GSK. MEW has received grants trials—are substantial. In paid to his institution from Regeneron, GSK, 1 Israel E, Wechsler ME, Jackson DJ, Moore WC. Anti-cytokine biologics for asthma in adults. randomised, double-blind studies AstraZeneca, Sanofi, and Upstream Bio; has received Lancet 2025; 406: 2282–94. of dupilumab and tezepelumab consulting fees from Allakos, Amgen, Areteia 2 Lommatzsch M, Buhl R, Bergmann K-C, et al. Therapeutics, Arrowhead Pharmaceutical, Avalo in oral corticosteroid-dependent Eosinophils in asthma phenotypes: Therapeutics, Belenos Bio, Celldex, Connect perpetrators or guilty by association? asthma, 25–46% of patients in the Biopharma, Eli Lilly, Equillium, Incyte, Jasper Lancet Respir Med 2025; 13: 943–50. placebo group had complete steroid Therapeutics, Kinaset, Kymera, Merck, MyBiometry, 3 Lommatzsch M, Criée C-P, de Jong CCM, et al. Pharming, Phylaxis, Pulmatrix, Rapt Therapeutics, reduction.3,4 In the German guidelines Diagnosis and treatment of asthma: a recludix Pharma, Roche/Genentech, Sentien, Sound guideline for respiratory specialists 2023 – study, the remission rate was 17% in Biologics, Tetherex Pharmaceuticals, Uniquity Bio, published by the German Respiratory Society those who did not receive any biologic Upstream Bio, Verona Pharma, and Zurabio; has (DGP) e. V. Pneumologie 2023; 77: 461–543. received payments or hononoria from AstraZeneca, treatment although those patients 4 Lommatzsch M, Buhl R, Canonica GW, et al. Sanofi, Regeneron, and GSK; has particpated in a data Pioneering a paradigm shift in asthma had not received a placebo. These data safety monitoring board for Sentien; and has stock management: remission as a treatment goal. underscore the difficulty of inferring options in Upstream Bio. WCM has received personal Lancet Respir Med 2024; 12: 96–99. fees for advisory board participation from AstraZeneca 5 Milger K, Suhling H, Skowasch D, et al. true drug-attributable remission rates and GSK; and research support paid to his institution Response to biologics and clinical remission in from observational cohorts lacking a (Wake Forest University) from the National Heart, the adult German Asthma Net severe asthma registry cohort. J Allergy Clin Immunol Pract placebo group. Lung, and Blood Institute, AstraZeneca, Boehringer 2023; 11: 2701–12. Against this background, our Ingelheim, GSK, Genentech, Sanofi-Regeneron, Areteia, Amgen, and TEVA. conclusion that current biologics Authors’ reply produce an absolute increase in *Elliot Israel, David J Jackson, Michael E Wechsler, Wendy C Moore We thank Katrin Milger and colleagues remission of only about 7–15% versus eisrael@bwh.harvard.edu for their thoughtful comments on our placebo in controlled trials1 remains, Series paper on anti-cytokine biologics in our view, appropriately cautious. Harvard Medical School, Brigham and Women’s Hospital, Division of Pulmonary and Critical Care and for severe asthma.1 We agree that Considering the high costs of biologics Allergy and Immunology, Boston, MA 02115, USA blood eosinophils should not be used for asthma, we strongly support (EI); Guy’s Severe Asthma Centre, School of in isolation and that multicomponent the call by Milger and colleagues Immunology & Microbial Sciences, Guy’s Hospital, King’s College London, London, UK (DJJ); The Cohen phenotyping—including age of for continued refinement and Family Asthma Institute, Denver, CO, USA (MEW); onset, allergic status, biomarkers, validation of phenotype-driven and Department of Medicine, Pulmonary, Critical Care and comorbidities—can help identify biomarker-driven algorithms. We also and Sleep Medicine, National Jewish Health, Denver, patients more likely to benefit from look forward to the development of CO, USA (MEW); Pulmonary, Critical Care, Allergy and Immunologic Diseases, Wake Forest University biologic therapy. However, the strongest newer biologics, with the hope that we School of Medicine, Winston-Salem, NC, USA (WCM) predictor of response remains the can further increase remission rates 1 Israel E, Wechsler ME, Jackson DJ, Moore WC. baseline level of type 2 inflammation. beyond those achievable with placebo Anti-cytokine biologics for asthma in adults. Milger and colleagues highlight the and optimised standard care. Lancet 2025; 406: 2282–94. 2 Milger K, Suhling H, Skowasch D, et al. German guideline-based algorithm EI has received research grants paid to his institution Response to biologics and clinical remission in and the impressive overall remission from AstraZeneca, the US National Institutes of Health the adult German Asthma Net severe asthma rates observed in the German Severe (NIH), the Patient-Centered Outcomes Research registry cohort. J Allergy Clin Immunol Pract Institute (PCORI) iCare, Sanofi, and TEVA; has received 2023; 11: 2701–12. Asthma Registry. However, even in royalties from UpToDate–Wolters Kluwer; has received 3 Rabe KF, Nair P, Brusselle G, et al. Efficacy and that carefully phenotyped but non- consulting fees from Amgen, AnaptyBio, Apogee safety of dupilumab in glucocorticoid randomised, unblinded study, the Therapeutics, Arrowhead Pharmaceuticals, dependent severe asthma. N Engl J Med 2018; 378: 2475–85. AstraZeneca, Bain Capital, Chiesi, Clearview Health absolute difference in remission Partners, Ecor1, Generate Biomedicine, GSK, 4 Wechsler ME, Menzies-Gow A, Brightling CE, between patients who received Guidepoint, Jasper Therapeutics, Leerink Partners, et al. Evaluation of the oral corticosteroid- sparing effect of tezepelumab in adults with biologics and those who did not was Merck, Mountainfield, OrbiMed, Reach Market oral corticosteroid-dependent asthma approximately 20%, and the remission Research, Regeneron, Sanofi, TEVA, Third Rock (SOURCE): a randomised, placebo-controlled, Ventures, Windrose Consulting Group, Wolters Kluwer, phase 3 study. Lancet Respir Med 2022; rate in patients who did not receive and Yuhan; has received payment or honoraria from 10: 650–60. any biologic treatment was still 17%.2 Aspen Allergy Conference, New York University; has participated on a data safety monitoring board for Thus, while enrichment clearly occurs, Amgen; has received stock options from Vorso the incremental benefit over (unpaid); has received equipment from Circassia and optimised non-biologic management study drugs from TEVA for the PCORI-PREPARE study; has received study drugs from Sun Pharma, Laurel remains modest. Pharmaceuticals, Om Pharma, Nestle, CSL Behring, --- [PDF原文](https://sci-net.xyz/storage/7932541/5e13f3784dd9ff63ed64931ed12cf39a737e1fb2265d5923dfd500a6625468c0/Clinical-phenotyping-improves-choices-of-biologics-in-asthma-Authors-reply.pdf) DOI: 10.1016/S0140-6736(26)00371-5