Clinical phenotyping improves choices of biologics in asthma.

# Clinical phenotyping improves choices of biologics in asthma *The Lancet 2026* Correspondence 8 Lewin SZ. Exhibit 5. Aug 3, 1972. https://cdn. existed then, nor do we have any variable and of minor pathogenetic toxicdocs.org/85/85JyymOw7EB568x1mExoq evidence that the editorial staff had any importance. In contrast, in intrinsic, RQVe/85JyymOw7EB568x1mExoqRQVe.pdf (accessed March 19, 2026). knowledge of the author’s affiliation non-allergic (typically adult-onset) 9 Spivak J. FDA plans to impose limits on with Johnson & Johnson. The author is asthma, eosinophilia is persistent and a asbestos in certain cosmetics. The Wall Street now deceased so we could not verify crucial driver of the disease. Accordingly, Journal, Feb 26, 1973. any of this with him. Despite not having biologics targeting eosinophils (either 10 The Cosmetic, Toiletry and Fragrance Association. CTFA Standards Committee. a complete record of The Lancet’s interleukin-5 or its receptor) are highly Aug 27, 1975. https://cdn.toxicdocs.org/V3/ previous editorial policies, Roe’s conflict effective in intrinsic phenotypes but V3pEx8RX2wqVY3BQXJMGqrq08/ V3pEx8RX2wqVY3BQXJMGqrq08.pdf of interest with Johnson & Johnson was not in allergic phenotypes of asthma, (accessed March 19, 2026). a clear breach of publishing ethics. In suggesting that blood eosinophil 11 Schwartz H. Document our view, had the editors at the time counts should not be used as a zoQjL87oyxvjNQ5D6LY3znQE0. Jan 18, 1973. https://www.toxicdocs.org/d/zoQjL87oyxvjNQ known of this situation and been aware standalone treatable trait in severe 5D6LY3znQE0?lightbox=1 (accessed of the author’s undeclared competing asthma but rather as a complement to March 19, 2026). 12 Cardillo v Chanel, Inc. Case number interest, they would not have accurate clinical phenotyping.2 2023-05986, part 33, testimony of Gerald published this commentary. The Lancet The algorithm for selecting biologics Markowitz, p 741. Supreme Court of the State of New York; NY, USA; Jan 11, 2024. has therefore decided to retract2 the published in the German asthma 13 Howarth P. Francis Roe 1924–2007. commentary. guidelines3,4 encompasses not only Toxicol Pathol 2007; 35: 851–52. eosinophils, exhaled nitric oxide, The Editors of The Lancet and comorbidities, but also the age editorial@lancet.com Editors’ reply of asthma onset and the presence The Lancet Group, London EC2Y 5AS, UK On Dec 8, 2025, we were informed of of clinically relevant allergies. This 1 No authors listed. Cosmetic talc powder. Published Online a serious conflict of interest in a Lancet Lancet 1977; 1: 1348–49. approach results in higher remission March 25, 2026 publication. We thank David Rosner 2 The Editors of The Lancet. Retraction: rates5 than those reported by Israel and https://doi.org/10.1016/ and Gerald Markowitz for their Cosmetic talc powder. Lancet 2026; published colleagues.1 S0140-6736(26)00559-3 online March 25. https://doi.org/10.1016/ rigorous investigation in drawing See Online/Correspondence S0140-6736(26)00552-0. KM received research grants from Bundesministerium https://doi.org/10.1016/ attention to an unsigned commentary für Bildung und Forschung; consulting and speaker S0140-6736(26)00558-1 published in 1977 in The Lancet,1 which frees from AstraZeneca, Chiesi, Insmed, GSK, and Clinical phenotyping Sanofi; and speaker fees from Novartis. JCV received See Online/Comment concluded that, “there is no reason research grants from Deutsche https://doi.org/10.1016/ to believe that normal consumer improves choices of Forschungsgemeinschaft, Land Mecklenburg– S0140-6736(26)00552-0 exposure to cosmetic talc has in the Vorpommern, GSK, and Merck Sharp Dohme; has biologics in asthma given independent lectures for and received past led either to cancer at any site or honoraria from AstraZeneca, Avontec, Bayer, Bencard, to measurable loss of lung function. It Bionorica, Boehringer Ingelheim, Chiesi, Essex/ seems unlikely that future exposure to We read with interest the Series paper Schering–Plough, GSK, Janssen–Cilag, Lupin, Leti, MEDA, Merck, Merck Sharp Dohme, Mundipharma, cosmetic talc of the specifications now by Elliot Israel and colleagues on Novartis, Nycomed/Altana, Pfizer, Regeneron, agreed to by major manufacturers will current biologic treatment options Revotar, Sandoz–Hexal, Sanofi–Aventis, Stallergens, present a health hazard”. in severe asthma.1 The authors use TEVA, UCB/Schwarz–Pharma, and Zydus/Cadila; and participated on advisory boards and provided Publishing unsigned commentaries blood eosinophil count thresholds—in independent advice for AstraZeneca, Avontec, Bayer, used to be standard practice. However, addition to assessing comorbidities— Bencard, Boehringer Ingelheim, Chiesi, Essex/ looking back at the published text as the main basis for their algorithm to Schering–Plough, GSK, Janssen–Cilag, MEDA, Merck Sharp Dohme, Mundipharma, Novartis, Regeneron, and the documents provided to select a targeted biologic treatment. Revotar, Roche, Sanofi–Aventis, Sandoz–Hexal, TEVA, The Lancet by Rosner and Markowitz, Furthermore, they compare the and UCB/Schwarz–Pharma. ML received grants for this commentary does indeed efficacy of biologics in clinical trials research or clinical trials, paid to his institution, from appear to have been authored by based solely on a blood eosinophil AstraZeneca, Deutsche Forschungsgemeinschaft, and GSK; and consulting fees, travel expenses, or See Online for appendix Francis J C Roe (appendix). The Lancet’s count threshold of 300 or more honoraria for lectures from ALK, Allergopharma, records show that the editor at the time eosinophils per µL. However, using AstraZeneca, Berlin–Chemie, Boehringer Ingelheim, had manually annotated an archived blood eosinophil thresholds alone to Chiesi, GSK, HAL Allergy, Leti, Novartis, Merck Sharp Dohme, Sanofi, Stallergenes, and Teva. copy of the journal with the full name compare biological efficacy falls short and address of the author, for the of the fact that the clinical significance *Katrin Milger, purpose of attributing payment. As of blood eosinophils depends strongly Johann Christian Virchow, Marek Lommatzsch the editors from 1977 are no longer on the clinical asthma phenotype,2 available to comment and we no which varies among the populations katrin.milger-kneidinger@medunigraz. longer have correspondence and files in the reported trials.1 at from that time, we are not aware of In allergen-driven (typically early- Division of Respiratory Medicine, Department of the competing interests policies that onset) asthma, eosinophil counts are Internal Medicine, Lung Research Cluster, Medical 1330 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/7932541/7be71f8b87fcd5ccf70cea3c96f101e3d7b075cdded13d1446ec945593523d92/Clinical-phenotyping-improves-choices-of-biologics-in-asthma.pdf) DOI: 10.1016/S0140-6736(26)00140-6