{"id":23716,"date":"2023-04-18T04:21:00","date_gmt":"2023-04-17T20:21:00","guid":{"rendered":"http:\/\/csccm.org.cn\/?p=23716"},"modified":"2023-04-18T05:29:16","modified_gmt":"2023-04-17T21:29:16","slug":"nejm%e5%8f%91%e8%a1%a8%e8%ae%ba%e6%96%87%ef%bc%9asotatercept%e6%b2%bb%e7%96%97%e8%82%ba%e5%8a%a8%e8%84%89%e9%ab%98%e5%8e%8b%e7%9a%843%e6%9c%9f%e4%b8%b4%e5%ba%8a%e8%af%95%e9%aa%8c","status":"publish","type":"post","link":"https:\/\/csccm.org.cn\/?p=23716","title":{"rendered":"[NEJM\u53d1\u8868\u8bba\u6587]\uff1aSotatercept\u6cbb\u7597\u80ba\u52a8\u8109\u9ad8\u538b\u76843\u671f\u4e34\u5e8a\u8bd5\u9a8c"},"content":{"rendered":"\n

ORIGINAL ARTICLE<\/a><\/p>\n\n\n\n

Phase 3 Trial of Sotatercept for Treatment of Pulmonary Arterial Hypertension<\/h1>\n\n\n\n

Marius M. Hoeper, David B. Badesch, H. Ardeschir Ghofrani,\u00a0et al<\/h3>\n\n\n\n

N Engl J Med March 6, 2023
DOI: 10.1056\/NEJMoa2213558<\/h3>\n\n\n\n

Abstract<\/h2>\n\n\n\n

BACKGROUND<\/h2>\n\n\n\n

Pulmonary arterial hypertension is a progressive disease involving proliferative remodeling of the pulmonary vessels. Despite therapeutic advances, the disease-associated morbidity and mortality remain high. Sotatercept is a fusion protein that traps activins and growth differentiation factors involved in pulmonary arterial hypertension.<\/p>\n\n\n\n

METHODS<\/h2>\n\n\n\n

We conducted a multicenter, double-blind, phase 3 trial in which adults with pulmonary arterial hypertension (World Health Organization [WHO] functional class II or III) who were receiving stable background therapy were randomly assigned in a 1:1 ratio to receive subcutaneous sotatercept (starting dose, 0.3 mg per kilogram of body weight; target dose, 0.7 mg per kilogram) or placebo every 3 weeks. The primary end point was the change from baseline at week 24 in the 6-minute walk distance. Nine secondary end points, tested hierarchically in the following order, were multicomponent improvement, change in pulmonary vascular resistance, change in N-terminal pro\u2013B-type natriuretic peptide level, improvement in WHO functional class, time to death or clinical worsening, French risk score, and changes in the Pulmonary Arterial Hypertension\u2013Symptoms and Impact (PAH-SYMPACT) Physical Impacts, Cardiopulmonary Symptoms, and Cognitive\u2013Emotional Impacts domain scores; all were assessed at week 24 except time to death or clinical worsening, which was assessed when the last patient completed the week 24 visit.<\/p>\n\n\n\n

RESULTS<\/h2>\n\n\n\n

A total of 163 patients were assigned to receive sotatercept and 160 to receive placebo. The median change from baseline at week 24 in the 6-minute walk distance was 34.4 m (95% confidence interval [CI], 33.0 to 35.5) in the sotatercept group and 1.0 m (95% CI, \u22120.3 to 3.5) in the placebo group. The Hodges\u2013Lehmann estimate of the difference between the sotatercept and placebo groups in the change from baseline at week 24 in the 6-minute walk distance was 40.8 m (95% CI, 27.5 to 54.1; P<0.001). The first eight secondary end points were significantly improved with sotatercept as compared with placebo, whereas the PAH-SYMPACT Cognitive\u2013Emotional Impacts domain score was not. Adverse events that occurred more frequently with sotatercept than with placebo included epistaxis, dizziness, telangiectasia, increased hemoglobin levels, thrombocytopenia, and increased blood pressure.<\/p>\n\n\n\n

\"\"\/<\/figure>\n\n\n\n
\"\"\/
Figure 1.\u00a0Change in 6-Minute Walk Distance through Week 24.<\/strong>The line graph shows the observed mean changes from baseline in 6-minute walk distance (in meters) in the sotatercept group (solid triangles) and placebo group (solid circles) with 95% confidence intervals (indicated by \ud835\ude78 bars). Walking distance was recorded at prespecified trial visits (i.e., week 0 [baseline], week 3, week 12, and week 24) during the first 24 weeks of the trial. The data shown are for patients with available data (observed) over time. The imputed median changes from baseline at week 24 for the prespecified and post hoc analyses are plotted as open symbols (open triangle for sotatercept and open circle for placebo). The prespecified and post hoc imputed medians are shown as open symbols with solid and dashed lines, respectively. For the prespecified analysis, missing values at week 24 owing to death or nonfatal clinical worsening events were assigned worst and second-worst rank scores, respectively. For the post hoc analysis, patients with missing values at week 24 owing to death were excluded from the analysis, whereas missing values owing to nonfatal clinical worsening events were imputed as the overall mean. For both the prespecified and post hoc analyses, missing values at week 24 owing to reasons other than death or nonfatal clinical worsening events were imputed with the use of standard multiple imputation with a fully conditional specification model in which the data were assumed to be missing at random (see the Statistical Analyses section in the\u00a0Supplementary Appendix<\/a>). The confidence intervals have not been adjusted for multiplicity and cannot be used to infer definitive treatment effects.<\/figcaption><\/figure>\n\n\n\n
\"\"\/<\/figure>\n\n\n\n
\"\"\/<\/figure>\n\n\n\n
\"\"\/<\/figure>\n\n\n\n

CONCLUSIONS<\/h2>\n\n\n\n

In patients with pulmonary arterial hypertension who were receiving stable background therapy, sotatercept resulted in a greater improvement in exercise capacity (as assessed by the 6-minute walk test) than placebo. (Funded by Acceleron Pharma, a subsidiary of MSD; STELLAR ClinicalTrials.gov number, NCT04576988. opens in new tab<\/a>.)<\/p>\n","protected":false},"excerpt":{"rendered":"

ORIGINAL ARTICLE Phase 3 Trial of Sotatercept for Treat […]<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":[],"categories":[32,23],"tags":[],"_links":{"self":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts\/23716"}],"collection":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=23716"}],"version-history":[{"count":1,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts\/23716\/revisions"}],"predecessor-version":[{"id":23717,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts\/23716\/revisions\/23717"}],"wp:attachment":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=23716"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=23716"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=23716"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}