{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T03:24:58Z","timestamp":1787196298976,"version":"build-2736575974"},"reference-count":32,"publisher":"Walter de Gruyter GmbH","license":[{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec id=\"j_jom-2026-0084_abs_001\">\n                    <jats:title>Context<\/jats:title>\n                    <jats:p>Severe asthma affects 3\u201310\u202f% of all asthma patients but accounts for disproportionately high morbidity and mortality. These patients tend to experience more frequent hospitalization compared to mild-to-moderate controlled asthmatics or the general population. Despite optimized inhaler therapy, many patients experience persistent symptoms and impaired lung function. Biologics targeting type-2 inflammation, including benralizumab, dupilumab, and tezepelumab, have emerged as add-on treatments that improve lung function and quality of life. Blood eosinophil count has been identified as a predictor of treatment response (i.e.,\u00a0\u2265150\u202fcells\/\u00b5L). Although individual randomized controlled trials have evaluated these biologics separately, no prior meta-analysis has compared their effects within a unified framework or systematically examined whether treatment benefits differ by baseline eosinophil levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_jom-2026-0084_abs_002\">\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      The objective of this meta-analysis was to evaluate the efficacy of benralizumab, dupilumab, and tezepelumab in adults with severe asthma. The primary outcome was the change in prebronchodilator forced expiratory volume in 1\u202fs (FEV\n                      <jats:sub>1<\/jats:sub>\n                      ). Secondary outcomes included the Asthma Control Questionnaire (ACQ) and Asthma Quality of Life Questionnaire (AQLQ) scores. Analyses were stratified by baseline blood eosinophil count (\u2265300 vs. &lt;300\u202fcells\/\u03bcL), with interaction testing to determine whether eosinophil levels modify treatment response.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_jom-2026-0084_abs_003\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A systematic literature search identified phase 3 randomized controlled trials evaluating benralizumab, dupilumab, and tezepelumab in adults with severe asthma. Data were extracted from the SIROCCO, QUEST, and PATHWAY\/NAVIGATOR trials. Pooled estimates were calculated utilizing a random-effects meta-analysis model. Continuous outcomes were summarized as mean differences with 95\u202f% confidence intervals (CIs), and subgroup analyses were performed by baseline eosinophil count (\u2265300 vs. &lt;300\u202fcells\/\u03bcL). Interaction was assessed utilizing Cochran\u2019s Q test for subgroup differences, with statistical significance defined as p&lt;0.05.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_jom-2026-0084_abs_004\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The pooled improvement in prebronchodilator FEV\n                      <jats:sub>1<\/jats:sub>\n                      was 0.133\u202fL (95\u202f% CI, 0.107\u20130.159; p&lt;0.001), exceeding the minimal clinically important difference (MCID) of 0.10\u202fL. Effects were comparable across agents: benralizumab 0.130\u202fL, dupilumab 0.132\u202fL, and tezepelumab 0.135\u202fL. The ACQ score improved by\u00a0\u22120.293 (95\u202f% CI,\u00a0\u22120.358 to\u00a0\u22120.227), and the AQLQ score increased by 0.283 (95\u202f% CI, 0.214\u20130.351). Patients with eosinophils\u00a0\u2265300\u202fcells\/\u03bcL had greater FEV\n                      <jats:sub>1<\/jats:sub>\n                      gains (0.201\u202fL; 95\u202f% CI, 0.165\u20130.237) than those with &lt;300\u202fcells\/\u03bcL (0.057\u202fL; 95\u202f% CI, 0.023\u20130.090), with significant subgroup heterogeneity (p&lt;0.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_jom-2026-0084_abs_005\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>All three biologics produced similar, clinically meaningful improvements in lung function. Higher baseline eosinophil counts predicted a greater response. Patient-reported outcomes improved modestly but did not reach MCID thresholds, possibly due to ceiling effects in patients already receiving maximal inhaler therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1515\/jom-2026-0084","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T02:56:17Z","timestamp":1787194577000},"source":"Crossref","is-referenced-by-count":0,"title":["Efficacy of benralizumab, dupilumab, and tezepelumab in severe asthma: a meta-analysis with eosinophil-stratified subgroup analysis"],"prefix":"10.1515","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7215-4445","authenticated-orcid":false,"given":"Ahmed","family":"Gamal","sequence":"first","affiliation":[{"name":"University Hospitals St. John Medical Center , Westlake , OH , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Hostoffer","sequence":"additional","affiliation":[{"name":"University Hospitals, Cleveland Medical Center , Cleveland , OH , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2026,8,20]]},"reference":[{"key":"2026082002561008443_j_jom-2026-0084_ref_001","unstructured":"Global Initiative for A. Diagnosis and management of difficult-to-treat & severe asthma. GINA Severe Asthma Guide. Fontana, USA: Global Initiative for Asthma; 2025."},{"key":"2026082002561008443_j_jom-2026-0084_ref_031","doi-asserted-by":"crossref","unstructured":"Barberio, J, Li, X, Sinnott, SJ. Comparing two approaches to identify individuals with severe asthma in United States claims data. Pharmacoepidemiol Drug Saf 2025;34:e70220.","DOI":"10.1002\/pds.70220"},{"key":"2026082002561008443_j_jom-2026-0084_ref_032","doi-asserted-by":"crossref","unstructured":"Hekking, PPW, Wener, RR, Amelink, M, Zwinderman, AH, Bouvy, ML, Bel, EH. The prevalence of severe refractory asthma. J Allergy Clin Immunol 2015;135:896\u2013902.","DOI":"10.1016\/j.jaci.2014.08.042"},{"key":"2026082002561008443_j_jom-2026-0084_ref_002","doi-asserted-by":"crossref","unstructured":"Burnette, A, Wang, Y, Rane, PB, Chung, Y, Princic, N, Park, J, et al.. Incremental cost burden among patients with severe uncontrolled asthma in the United\u00a0States. J\u00a0Manag Care Spec Pharm 2023;29:825\u201334. https:\/\/doi.org\/10.18553\/jmcp.2023.29.7.825.","DOI":"10.18553\/jmcp.2023.29.7.825"},{"key":"2026082002561008443_j_jom-2026-0084_ref_003","doi-asserted-by":"crossref","unstructured":"Chung, KF, Wenzel, SE, Brozek, JL, Bush, A, Castro, M, Sterk, PJ, et al.. International ERS\/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J 2014;43:343\u201373. https:\/\/doi.org\/10.1183\/09031936.00202013.","DOI":"10.1183\/09031936.00202013"},{"key":"2026082002561008443_j_jom-2026-0084_ref_004","doi-asserted-by":"crossref","unstructured":"Wang, E, Wechsler, ME, Tran, TN, Heaney, LG, Jones, RC, Menzies-Gow, AN, et al.. Characterization of severe asthma worldwide: data from the International Severe Asthma Registry. Chest 2020;157:790\u2013804. https:\/\/doi.org\/10.1016\/j.chest.2019.10.053.","DOI":"10.1016\/j.chest.2019.10.053"},{"key":"2026082002561008443_j_jom-2026-0084_ref_005","doi-asserted-by":"crossref","unstructured":"Hansen, S, von Bulow, A, Cooper, A, Sandin, P, Ernstsson, O, Kankaanranta, H, et al.. Mortality in severe asthma: results from the NORDSTAR cohort. Eur Respir J 2026;67:2501289. https:\/\/doi.org\/10.1183\/13993003.01289-2025.","DOI":"10.1183\/13993003.01289-2025"},{"key":"2026082002561008443_j_jom-2026-0084_ref_006","doi-asserted-by":"crossref","unstructured":"Mosnaim, G. Asthma in adults. N\u00a0Engl J Med 2023;389:1023\u201331. https:\/\/doi.org\/10.1056\/nejmcp2304871.","DOI":"10.1056\/NEJMcp2304871"},{"key":"2026082002561008443_j_jom-2026-0084_ref_007","doi-asserted-by":"crossref","unstructured":"Israel, E, Wechsler, ME, Jackson, DJ, Moore, WC. Anti-cytokine biologics for asthma in adults. Lancet 2025;406:2282\u201394. https:\/\/doi.org\/10.1016\/s0140-6736(25)01625-3.","DOI":"10.1016\/S0140-6736(25)01625-3"},{"key":"2026082002561008443_j_jom-2026-0084_ref_008","doi-asserted-by":"crossref","unstructured":"Fahy, JV. Type 2 inflammation in asthma--present in most, absent in many. Nat Rev Immunol 2015;15:57\u201365. https:\/\/doi.org\/10.1038\/nri3786.","DOI":"10.1038\/nri3786"},{"key":"2026082002561008443_j_jom-2026-0084_ref_009","doi-asserted-by":"crossref","unstructured":"Chiang, DT, Clark, J, Casale, TB. Omalizumab in asthma: approval and\u00a0postapproval experience. Clin Rev Allergy Immunol 2005;29:3\u201316. https:\/\/doi.org\/10.1385\/criai:29:1:003.","DOI":"10.1385\/CRIAI:29:1:003"},{"key":"2026082002561008443_j_jom-2026-0084_ref_010","doi-asserted-by":"crossref","unstructured":"Wechsler, ME, Ruddy, MK, Pavord, ID, Israel, E, Rabe, KF, Ford, LB, et al.. Efficacy and safety of itepekimab in patients with moderate-to-severe asthma. N\u00a0Engl J Med 2021;385:1656\u201368. https:\/\/doi.org\/10.1056\/nejmoa2024257.","DOI":"10.1056\/NEJMoa2024257"},{"key":"2026082002561008443_j_jom-2026-0084_ref_011","doi-asserted-by":"crossref","unstructured":"Gauvreau, GM, O\u2019Byrne, PM, Boulet, LP, Wang, Y, Cockcroft, D, Bigler, J, et al.. Effects of an anti-TSLP antibody on allergen-induced asthmatic responses. N\u00a0Engl J Med 2014;370:2102\u201310. https:\/\/doi.org\/10.1056\/nejmoa1402895.","DOI":"10.1056\/NEJMoa1402895"},{"key":"2026082002561008443_j_jom-2026-0084_ref_012","doi-asserted-by":"crossref","unstructured":"Menzies-Gow, A, Corren, J, Bourdin, A, Chupp, G, Israel, E, Wechsler, ME, et al.. Tezepelumab in adults and adolescents with severe, uncontrolled asthma. N\u00a0Engl J Med 2021;384:1800\u20139. https:\/\/doi.org\/10.1056\/nejmoa2034975.","DOI":"10.1056\/NEJMoa2034975"},{"key":"2026082002561008443_j_jom-2026-0084_ref_013","doi-asserted-by":"crossref","unstructured":"Page, MJ, McKenzie, JE, Bossuyt, PM, Boutron, I, Hoffmann, TC, Mulrow, CD, et al.. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021;372:n71. https:\/\/doi.org\/10.1136\/bmj.n71.","DOI":"10.1136\/bmj.n71"},{"key":"2026082002561008443_j_jom-2026-0084_ref_014","doi-asserted-by":"crossref","unstructured":"Santanello, NC, Zhang, J, Seidenberg, B, Reiss, TF, Barber, BL. What are minimal important changes for asthma measures in a clinical trial? Eur Respir J 1999;14:23\u20137. https:\/\/doi.org\/10.1034\/j.1399-3003.1999.14a06.x.","DOI":"10.1034\/j.1399-3003.1999.14a06.x"},{"key":"2026082002561008443_j_jom-2026-0084_ref_015","doi-asserted-by":"crossref","unstructured":"Kim, LHY, Saleh, C, Whalen-Browne, A, O\u2019Byrne, PM, Chu, DK. Triple vs dual inhaler therapy and asthma outcomes in moderate to severe asthma: a systematic review and meta-analysis. JAMA 2021;325:2466\u201379. https:\/\/doi.org\/10.1001\/jama.2021.7872.","DOI":"10.1001\/jama.2021.7872"},{"key":"2026082002561008443_j_jom-2026-0084_ref_016","doi-asserted-by":"crossref","unstructured":"Holguin, F, Cardet, JC, Chung, KF, Diver, S, Ferreira, DS, Fitzpatrick, A, et al.. Management of severe asthma: a European Respiratory Society\/American Thoracic Society guideline. Eur Respir J 2020;55:1900588. https:\/\/doi.org\/10.1183\/13993003.00588-2019.","DOI":"10.1183\/13993003.00588-2019"},{"key":"2026082002561008443_j_jom-2026-0084_ref_017","doi-asserted-by":"crossref","unstructured":"Tepper, RS, Wise, RS, Covar, R, Irvin, CG, Kercsmar, CM, Kraft, M, et al.. Asthma outcomes: pulmonary physiology. J\u00a0Allergy Clin Immunol 2012;129:S65\u201387. https:\/\/doi.org\/10.1016\/j.jaci.2011.12.986.","DOI":"10.1016\/j.jaci.2011.12.986"},{"key":"2026082002561008443_j_jom-2026-0084_ref_018","doi-asserted-by":"crossref","unstructured":"Corren, J, Menzies-Gow, A, Chupp, G, Israel, E, Korn, S, Cook, B, et al.. Efficacy of tezepelumab in severe, uncontrolled asthma: pooled analysis of the PATHWAY and NAVIGATOR clinical trials. Am J Respir Crit Care Med 2023;208:13\u201324. https:\/\/doi.org\/10.1164\/rccm.202210-2005oc.","DOI":"10.1164\/rccm.202210-2005OC"},{"key":"2026082002561008443_j_jom-2026-0084_ref_019","doi-asserted-by":"crossref","unstructured":"Bleecker, ER, FitzGerald, JM, Chanez, P, Papi, A, Weinstein, SF, Barker, P, et al.. Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting beta(2)-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial. Lancet 2016;388:2115\u201327. https:\/\/doi.org\/10.1016\/s0140-6736(16)31324-1.","DOI":"10.1016\/S0140-6736(16)31324-1"},{"key":"2026082002561008443_j_jom-2026-0084_ref_020","doi-asserted-by":"crossref","unstructured":"Castro, M, Corren, J, Pavord, ID, Maspero, J, Wenzel, S, Rabe, KF, et al.. Dupilumab efficacy and safety in moderate-to-severe uncontrolled asthma. N\u00a0Engl J Med 2018;378:2486\u201396. https:\/\/doi.org\/10.1056\/nejmoa1804092.","DOI":"10.1056\/NEJMoa1804092"},{"key":"2026082002561008443_j_jom-2026-0084_ref_021","doi-asserted-by":"crossref","unstructured":"Bonini, M, Di Paolo, M, Bagnasco, D, Baiardini, I, Braido, F, Caminati, M, et al.. Minimal clinically important difference for asthma endpoints: an expert consensus report. Eur Respir Rev 2020;29:190137. https:\/\/doi.org\/10.1183\/16000617.0137-2019.","DOI":"10.1183\/16000617.0137-2019"},{"key":"2026082002561008443_j_jom-2026-0084_ref_022","doi-asserted-by":"crossref","unstructured":"Reddel, HK, Taylor, DR, Bateman, ED, Boulet, LP, Boushey, HA, Busse, WW, et al.. An official American Thoracic Society\/European Respiratory Society statement: asthma control and exacerbations: standardizing endpoints for clinical asthma trials and clinical practice. Am J Respir Crit Care Med 2009;180:59\u201399. https:\/\/doi.org\/10.1164\/rccm.200801-060st.","DOI":"10.1164\/rccm.200801-060ST"},{"key":"2026082002561008443_j_jom-2026-0084_ref_023","doi-asserted-by":"crossref","unstructured":"Ogulur, I, Mitamura, Y, Yazici, D, Pat, Y, Ardicli, S, Li, M, et al.. Type 2 immunity in allergic diseases. Cell Mol Immunol 2025;22:211\u201342. https:\/\/doi.org\/10.1038\/s41423-025-01261-2.","DOI":"10.1038\/s41423-025-01261-2"},{"key":"2026082002561008443_j_jom-2026-0084_ref_024","doi-asserted-by":"crossref","unstructured":"Chiarella, SE, Novoa-Caicedo, I, Pongdee, T, Wi, CI, Juhn, YJ. Biomarkers for selecting biologic therapies in asthma. Ther Adv Respir Dis 2026;20:17534666261430646. https:\/\/doi.org\/10.1177\/17534666261430646.","DOI":"10.1177\/17534666261430646"},{"key":"2026082002561008443_j_jom-2026-0084_ref_025","doi-asserted-by":"crossref","unstructured":"Bleecker, ER, Wechsler, ME, FitzGerald, JM, Menzies-Gow, A, Wu, Y, Hirsch, I, et al.. Baseline patient factors impact on the clinical efficacy of benralizumab for severe asthma. Eur Respir J 2018;52:1800936. https:\/\/doi.org\/10.1183\/13993003.00936-2018.","DOI":"10.1183\/13993003.00936-2018"},{"key":"2026082002561008443_j_jom-2026-0084_ref_026","doi-asserted-by":"crossref","unstructured":"Corren, J, Pham, TH, Garcia, GE, Sa\u0142apa, K, Ren, P, Parnes, JR, et al.. Baseline type 2 biomarker levels and response to tezepelumab in severe asthma. Allergy 2022;77:1786\u201396. https:\/\/doi.org\/10.1111\/all.15197.","DOI":"10.1111\/all.15197"},{"key":"2026082002561008443_j_jom-2026-0084_ref_027","doi-asserted-by":"crossref","unstructured":"Wenzel, S, Ford, L, Pearlman, D, Spector, S, Sher, L, Skobieranda, F, et al.. Dupilumab in persistent asthma with elevated eosinophil levels. N\u00a0Engl J Med 2013;368:2455\u201366. https:\/\/doi.org\/10.1056\/nejmoa1304048.","DOI":"10.1056\/NEJMoa1304048"},{"key":"2026082002561008443_j_jom-2026-0084_ref_028","doi-asserted-by":"crossref","unstructured":"Pelaia, C, Calabrese, C, Vatrella, A, Busceti, MT, Garofalo, E, Lombardo, N, et al.. Benralizumab: from the basic mechanism of action to the potential use in the biological therapy of severe eosinophilic asthma. Biomed Res Int 2018;2018:4839230. https:\/\/doi.org\/10.1155\/2018\/4839230.","DOI":"10.1155\/2018\/4839230"},{"key":"2026082002561008443_j_jom-2026-0084_ref_029","doi-asserted-by":"crossref","unstructured":"Corren, J, Karpefors, M, Hellqvist, A, Parnes, JR, Colice, G. Tezepelumab reduces exacerbations across all seasons in patients with severe, uncontrolled asthma: a post hoc analysis of the PATHWAY phase 2b study. J\u00a0Asthma Allergy 2021;14:1\u201311. https:\/\/doi.org\/10.2147\/jaa.s286036.","DOI":"10.2147\/JAA.S286036"},{"key":"2026082002561008443_j_jom-2026-0084_ref_030","doi-asserted-by":"crossref","unstructured":"Carr, TF, Moore, WC, Kraft, M, Brusselle, G, Castro, M, Chupp, GL, et al.. Efficacy of tezepelumab in patients with severe, uncontrolled asthma across multiple clinically relevant subgroups in the NAVIGATOR study. Adv Ther 2024;41:2978\u201390. https:\/\/doi.org\/10.1007\/s12325-024-02889-8.","DOI":"10.1007\/s12325-024-02889-8"}],"container-title":["Journal of Osteopathic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/jom-2026-0084\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/jom-2026-0084\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T02:56:30Z","timestamp":1787194590000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/jom-2026-0084\/html"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,20]]},"references-count":32,"alternative-id":["10.1515\/jom-2026-0084"],"URL":"https:\/\/doi.org\/10.1515\/jom-2026-0084","relation":{},"ISSN":["2702-3648"],"issn-type":[{"value":"2702-3648","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,20]]}}}