{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:27:19Z","timestamp":1790774839246,"version":"4.1.0"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100004334","name":"Merck","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004334","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004334","name":"Merck","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004334","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004334","name":"Merck","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004334","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004334","name":"Merck","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004334","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>It is unclear whether carriers of pathogenic variants in PAH-associated genes have a distinct response to PAH treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To evaluate the effect of genetic variant status on the efficacy of sotatercept and the effect of sotatercept treatment on biomarkers in pulmonary arterial hypertension.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>PULSAR (A Study of Sotatercept for the Treatment of Pulmonary Arterial Hypertension; NCT03496207) was a phase II, randomized controlled study of sotatercept versus placebo added to background therapy for pulmonary arterial hypertension. Participants underwent DNA sequencing at baseline to detect genetic variants in disease-associated genes (ACVRL1, BMPR2, CAV1, EIF2AK4, ENG, KCNA3, KCNK3, and SMAD9). Safety (adverse events) and efficacy (pulmonary vascular resistance, 6-min-walk distance) were assessed by variant status and treatment at 24 weeks. Serum concentrations of BMPR2 mRNA and N-terminal prohormone B-type natriuretic peptide were assessed at baseline and 24 weeks by treatment and variant status. Analysis of covariance was used to compare the change from baseline by treatment and variant status.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>Among 76 participants included, pathogenic variants were detected in 25 (23 BMPR2, 2 other), and 51 had no variants or variants of uncertain significance. BMPR2 mutation carriers were younger and more frequently on triple therapy but had less severe clinical characteristics at baseline. Changes at 24 weeks in pulmonary vascular resistance and 6-minute-walk distance did not differ by variant status. BMPR2 gene expression varied less than twofold from baseline over time, irrespective of treatment or variant status. The adverse event profile was generally consistent with that seen in the parent PULSAR study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These results suggest consistent safety and clinical efficacy of sotatercept for treatment of pulmonary arterial hypertension, irrespective of BMPR2 variant status.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.202409-1698oc","type":"journal-article","created":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T09:33:26Z","timestamp":1741080806000},"page":"1028-1037","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":21,"title":["Consistent Safety and Efficacy of Sotatercept for Pulmonary Arterial Hypertension in\n                    <i>BMPR2<\/i>\n                    Mutation Carriers and Noncarriers: A Planned Analysis of a Phase II, Double-Blind, Placebo-controlled Clinical Trial (PULSAR)"],"prefix":"10.1093","volume":"211","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9358-6922","authenticated-orcid":false,"given":"David","family":"Montani","sequence":"first","affiliation":[{"name":"Universit\u00e9 Paris-Saclay, INSERM Unit\u00e9 Mixte de Recherche en Sant\u00e9 999, Hypertension Pulmonaire: Physiopathologie et Innovation Th\u00e9rapeutique (HPPIT), Service de Pneumologie et Soins Intensifs Respiratoires, H\u00f4pital Bic\u00eatre (Assistance Publique\u2013H\u00f4pitaux de Paris), European Reference Network for Rare Respiratory Diseases (ERN-LUNG), Le Kremlin-Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8907-1651","authenticated-orcid":false,"given":"Vallerie V.","family":"McLaughlin","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6147-9252","authenticated-orcid":false,"given":"J. Simon R.","family":"Gibbs","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute, Imperial College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0482-4560","authenticated-orcid":false,"given":"Mardi","family":"Gomberg-Maitland","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, George Washington University, Washington, District of Columbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9086-2293","authenticated-orcid":false,"given":"Marius M.","family":"Hoeper","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine and Infectious Diseases, Hannover Medical School and German Center for Lung Research, Hannover, 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