马西替坦和他达拉非联合疗法在肺动脉高压发病率和流行率中的应用：来自 OPUS/OrPHeUS 研究的真实世界证据。

IF 3.4 3区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Advances in Therapy Pub Date : 2024-09-24 DOI:10.1007/s12325-024-02964-0

Kelly M. Chin, Richard Channick, Nick H. Kim, Gwen MacDonald, Rose Ong, Nicolas Martin, Assunta Senatore, Vallerie V. McLaughlin

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引用次数: 0

摘要

导言：从历史上看，近期（≤ 6 个月）确诊的肺动脉高压（PAH；偶发）患者的存活率低于确诊 PAH 时间较长（> 6 个月）的患者（流行）。尽管指南建议对大多数 PAH 患者进行初始联合治疗，但仍有许多患者开始并坚持单药治疗。目前还缺乏真实世界的证据来评估早期联合治疗对新诊断患者的益处：从美国多中心 OPUS（前瞻性、观察性药物登记；NCT02126943）和 OrPHeUS（回顾性、病历回顾；NCT03197688）研究（2013-2020 年）的合并数据集中确定了开始接受内皮素受体拮抗剂马西替坦和磷酸二酯酶-5 抑制剂他达拉非（M+T）联合治疗的 PAH 患者。对事件队列和流行队列以及接受M+T作为一线联合疗法的事件患者亚队列（事件初始联合疗法）进行了描述性分析：在 OPUS/OrPHeUS 观察期内，1336 名 PAH 患者接受了 M+T。事件组[n = 453 (33.9%)]、事件初始联合组[n = 272 (20.4%)]和流行组[n = 837 (62.6%)]：M+T接触中位数（Q1、Q3）分别为14.2 (4.2、27.5)、12.2 (3.2、25.5)和14.7 (4.5、28.0)个月。12个月的卡普兰-梅耶估计存活率（95%置信区间）分别为91.2%（87.7，93.7）、88.5%（83.2，92.2）和92.9%（90.6，94.6），未住院患者的存活率分别为59.4%（54.1，64.4%）、88.5%（83.2，92.2）和92.9%（90.6，94.6）。4%（54.1, 64.4）、56.3%（49.1, 62.9）和 62.3%（58.5, 65.9），而坚持接受联合治疗的患者为 68.6%（63.9, 72.8）、65.0%（58.8, 70.6）和 66.9%（63.5, 70.0）。分别有77.8%、80.2%和80.3%的患者报告了不良事件（仅OPUS），未观察到意外不良事件：结论：尽管预后历来较差，但接受M+T（包括作为初始联合疗法）治疗的事件患者的存活率和住院率与患病患者相似。各组群的安全性相似。总之，这些数据支持使用马西替坦和他达拉非进行早期联合治疗。

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Macitentan and Tadalafil Combination Therapy in Incident and Prevalent Pulmonary Arterial Hypertension: Real-World Evidence from the OPUS/OrPHeUS Studies

Introduction

Historically, patients recently (≤ 6 months) diagnosed with pulmonary arterial hypertension (PAH; incident) have had poorer survival than those with a longer (> 6 months) time from PAH diagnosis (prevalent). Despite guideline recommendations for initial combination therapy for most patients with PAH, many are initiated and maintained on monotherapy. Real-world evidence to evaluate the benefit of early combination treatment in newly-diagnosed patients is lacking.

Methods

Patients with PAH initiating combination therapy with the endothelin receptor antagonist macitentan and the phosphodiesterase-5 inhibitor tadalafil (M+T) were identified from the combined dataset of the US, multicenter OPUS (prospective, observational drug registry; NCT02126943) and OrPHeUS (retrospective, medical chart review; NCT03197688) studies (2013–2020). Descriptive analyses were performed for the incident and prevalent cohorts, as well as the subcohort of incident patients who received M+T as first-line combination therapy (incident initial combination).

Results

In OPUS/OrPHeUS, 1336 patients with PAH received M+T during the observation period. For the incident [n = 453 (33.9%)], incident initial combination [n = 272 (20.4%)], and prevalent [n = 837 (62.6%)] cohorts: median (Q1, Q3) M+T exposure was 14.2 (4.2, 27.5), 12.2 (3.2, 25.5), and 14.7 (4.5, 28.0) months. 12-month Kaplan–Meier estimates (95% confidence limits) for survival were 91.2% (87.7, 93.7), 88.5% (83.2, 92.2), and 92.9% (90.6, 94.6), for patients free from hospitalization were 59.4% (54.1, 64.4), 56.3% (49.1, 62.9), and 62.3% (58.5, 65.9), and for patients persisting on combination therapy were 68.6% (63.9, 72.8), 65.0% (58.8, 70.6) and 66.9% (63.5, 70.0). Adverse events (OPUS only) were reported in 77.8%, 80.2%, and 80.3% of patients, respectively, with no unexpected adverse events observed.

Conclusions

Despite a historically worse prognosis, incident patients receiving M+T, including as initial combination therapy, had similar survival and hospitalization as prevalent patients. Safety profiles were similar across cohorts. Together, these data support the use of early combination therapy with macitentan and tadalafil.

Graphical Abstract

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来源期刊

Advances in Therapy 医学-药学

CiteScore

7.20

自引率

2.60%

发文量

353

审稿时长

6-12 weeks

期刊介绍： Advances in Therapy is an international, peer reviewed, rapid-publication (peer review in 2 weeks, published 3–4 weeks from acceptance) journal dedicated to the publication of high-quality clinical (all phases), observational, real-world, and health outcomes research around the discovery, development, and use of therapeutics and interventions (including devices) across all therapeutic areas. Studies relating to diagnostics and diagnosis, pharmacoeconomics, public health, epidemiology, quality of life, and patient care, management, and education are also encouraged. The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, communications and letters. The journal is read by a global audience and receives submissions from all over the world. Advances in Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an international and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of all scientifically and ethically sound research.