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NATRON was a randomized, double-blind placebo-controlled phase 3 study evaluating the efficacy and safety of benralizumab in\n                    <jats:italic>FIP1L1::PDGFRA<\/jats:italic>\n                    -negative HES. The primary endpoint was time to first HES flare. In total, 133 patients (median (range) age 51 (14\u201387) years, 62% female) were randomized (1:1) to receive benralizumab 30\u2009mg every 4\u2009weeks or placebo for 24\u2009weeks, in addition to background therapy. Benralizumab significantly reduced the risk of first flare versus placebo (hazard ratio 0.35, 95% CI 0.18 to 0.69,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.0024). Adverse events occurred in 64.2% and 66.7% of benralizumab- and placebo-treated patients, respectively. Benralizumab\u2019s safety was consistent with its known profile. These results demonstrate the efficacy and safety of add-on benralizumab in the treatment of HES. ClinicalTrials.gov identifier:\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\/ct2\/show\/NCT04191304\" ext-link-type=\"uri\">NCT04191304<\/jats:ext-link>\n                    .\n                  <\/jats:p>","DOI":"10.1038\/s41591-026-04315-8","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T09:02:39Z","timestamp":1774947759000},"page":"2017-2025","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Benralizumab versus placebo for hypereosinophilic syndrome: a randomized, placebo-controlled phase 3 trial"],"prefix":"10.1038","volume":"32","author":[{"given":"Princess U.","family":"Ogbogu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Roufosse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Praveen","family":"Akuthota","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2401-0070","authenticated-orcid":false,"given":"Piotr","family":"Kuna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthieu","family":"Groh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Reiter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Yokota","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salman H.","family":"Siddiqui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pim G. 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F.R. has received consulting fees from GSK, AstraZeneca and Merck; honoraria from AstraZeneca and GSK; and royalties from UpToDate. P.A. has received grant funding from AstraZeneca, Sanofi and Recode, as well as consulting fees from AstraZeneca, Connect Biopharma, Sanofi, Regeneron, GSK, Amgen, Vida Ventures and Enveda. P. Kuna has received honoraria from Adamed, Angellini, AstraZeneca, Berlin Chemie Menarini, Glenmark, Chiesi, GSK, Celon Pharma, Polpharma, Sanofi and Teva. M.G. has received consulting fees from AstraZeneca and GSK. A.R. has received grant funding from Abbvie, AOP, AstraZeneca, BMS, Blueprint Medicines, GSK and Incyte; consulting fees from Abbvie, AOP, AstraZeneca, BMS, Blueprint Medicines, GSK, Incyte and Novartis; and honoraria from AOP, AstraZeneca, BMS, Blueprint Medicines, GSK and Novartis. S.H.S. has received consulting fees from AstraZeneca, GSK, Areteia Therapeutics, Sanofi and Chiesi; honoraria from AstraZeneca, GSK, Chiesi and Medscape; and has a patent in breath analysis and biomarkers submitted at the time of writing. P.G.N.J.M. has received grant funding from AstraZeneca. L.M.B. is employed by AstraZeneca and may hold stock in AstraZeneca. A.B. is employed by AstraZeneca and holds stock in AstraZeneca, Pfizer and GSK. G.B. is employed by AstraZeneca and may hold stock in AstraZeneca. L.G.B. is employed by AstraZeneca and may hold stock in AstraZeneca. J.F. is employed by AstraZeneca and may hold stock in AstraZeneca. H.G. is employed by AstraZeneca and may hold stock in AstraZeneca. C.N.H. is employed by AstraZeneca and may hold stock in AstraZeneca. P.J. is employed by AstraZeneca and may hold stock in AstraZeneca. R.L.P. is employed by AstraZeneca and may hold stock in AstraZeneca. M.L.J. is employed by AstraZeneca and may hold stock in AstraZeneca. A.D.K. has received royalties from UpToDate. The other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}