{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T05:53:24Z","timestamp":1793944404991,"version":"4.8.0"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2021,8,1]],"date-time":"2021-08-01T00:00:00Z","timestamp":1627776000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Pulmonary hypertension (PH) has been described in patients treated with leflunomide.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To assess the association between leflunomide and PH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We identified incident cases of PH in patients treated with leflunomide from the French PH Registry and through the pharmacoVIGIlAnce in Pulmonary ArTerial Hypertension (VIGIAPATH) program between September 1999 to December 2019. PH etiology, clinical, functional, radiologic, and hemodynamic characteristics were reviewed at baseline and follow-up. A pharmacovigilance disproportionality analysis using the World Health Organization\u2019s global database was conducted. We then investigated the effect of leflunomide on human pulmonary endothelial cells. Data are expressed as median (min\u2013max).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Twenty-eight patients treated with leflunomide before PH diagnosis was identified. A total of 21 (75%) had another risk factor for PH and 2 had two risk factors. The median time between leflunomide initiation and PH diagnosis was 32 months (1\u2013120). Right heart catheterization confirmed precapillary PH with a cardiac index of 2.37 L\u22c5min\u22121 \u22c5m\u22122 (1.19\u20133.1) and elevated pulmonary vascular resistance at 9.63 Wood Units (3.6\u201322.1) without nitric oxide reversibility. Five patients (17.9%) had no other risk factor for PH besides exposure to leflunomide. No significant hemodynamic improvement was observed after leflunomide withdrawal. The pharmacovigilance disproportionality analysis using the World Health Organization\u2019s database revealed a significant overrepresentation of leflunomide among reported pulmonary arterial hypertension\u2013adverse drug reactions. In vitro studies showed the dose-dependent toxicity of leflunomide on human pulmonary endothelial cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>PH associated with leflunomide is rare and usually associated with other risk factors. The pharmacovigilance analysis suggests an association reinforced by experimental data.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1513\/annalsats.202008-913oc","type":"journal-article","created":{"date-parts":[[2021,1,26]],"date-time":"2021-01-26T13:21:52Z","timestamp":1611667312000},"page":"1306-1315","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":18,"title":["Association between Leflunomide and Pulmonary Hypertension"],"prefix":"10.1093","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3543-6675","authenticated-orcid":false,"given":"Thomas Lacoste","family":"Palasset","sequence":"first","affiliation":[{"name":"Service de Pneumologie, Centre de R\u00e9f\u00e9rence de l\u2019Hypertension Pulmonaire, and"},{"name":"Universit\u00e9 Paris-Saclay, Le Kremlin-Bic\u00eatre, France"},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale Unit\u00e9 Mixte de Recherche_S 999, H\u00f4pital Marie Lannelongue, Le Plessis-Robinson, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1217-8442","authenticated-orcid":false,"given":"Marie-Camille","family":"Chaumais","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale Unit\u00e9 Mixte de Recherche_S 999, H\u00f4pital Marie Lannelongue, Le Plessis-Robinson, France"},{"name":"Service de Pharmacie, Centre Hospitalier Universitaire de Bic\u00eatre, Assistance Publique H\u00f4pitaux de Paris, Le Kremlin-Bic\u00eatre, France"},{"name":"Facult\u00e9 de Pharmacie, Universit\u00e9 Paris-Saclay, Chatenay-Malabry, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0615-4575","authenticated-orcid":false,"given":"Jason","family":"Weatherald","sequence":"additional","affiliation":[{"name":"Division of Respirology, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Savale","sequence":"additional","affiliation":[{"name":"Service de Pneumologie, Centre de R\u00e9f\u00e9rence de l\u2019Hypertension Pulmonaire, and"},{"name":"Universit\u00e9 Paris-Saclay, Le Kremlin-Bic\u00eatre, France"},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale Unit\u00e9 Mixte de Recherche_S 999, H\u00f4pital Marie Lannelongue, Le Plessis-Robinson, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Ja\u00efs","sequence":"additional","affiliation":[{"name":"Service de Pneumologie, Centre de R\u00e9f\u00e9rence de l\u2019Hypertension Pulmonaire, and"},{"name":"Universit\u00e9 Paris-Saclay, Le Kremlin-Bic\u00eatre, France"},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale Unit\u00e9 Mixte de Recherche_S 999, H\u00f4pital Marie Lannelongue, Le Plessis-Robinson, 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