Inhaled Treprostinil Dosage in Pulmonary Hypertension Associated With Interstitial Lung Disease and Its Effects on Clinical Outcomes.
Inhaled Treprostinil Dosage in Pulmonary Hypertension Associated With Interstitial Lung Disease and Its Effects on Clinical Outcomes.
复制标题
DOI：
10.1016/j.chest.2022.09.007
复制
发表时间：
2023-02
期刊：
影响因子：
9.6
通讯作者：
Waxman, Aaron B.
中科院分区：
文献类型：
--
作者：
Nathan, Steven D.;Deng, Chunqin;King, Christopher S.;DuBrock, Hilary M.;Elwing, Jean;Rajagopal, Sudarshan;Rischard, Franz;Sahay, Sandeep;Broderick, Meredith;Shen, Eric;Smith, Peter;Tapson, Victor F.;Waxman, Aaron B.
肺高压(PH)使许多纤维化间质性肺疾病(ILD)患者的病程复杂化。吸入曲普替尼(ITRE)已被证明可以改善ILD引起的PH患者的功能能力和延缓临床恶化。更大剂量的ITRE在预防临床恶化和实现临床改善方面是否有更大的好处？该研究是一项为期16周的双盲、随机、安慰剂对照试验，用于ILD引起的PH患者的ITRE。根据4周时获得的活性药物或安慰剂的每次呼吸次数(Bps；9和≥9)，确定了四组。对患者进行临床恶化(6分钟步行距离减少15%、心肺住院、肺移植或死亡)或临床改善(6分钟步行距离增加15%伴随着30%脑钠素前激素减少而没有任何临床恶化事件)进行评估。在4周时，70名患者的≥剂量为9 Gbps(高剂量组)，79名患者的Itre手臂剂量为9 Gbps(低剂量组)，而安慰剂组为786名患者和67名患者。在第4周和第16周，大剂量曲普替尼组和低剂量治疗组分别有17.1%和22.8%的患者经历了临床恶化事件，而两个安慰剂组的患者分别为33.7%和34.3%(P=0.006)。到第16周时，高剂量和低剂量ITRE组分别有15.7%和12.7%的患者表现出临床改善，而安慰剂组分别为17.7%和1.5%(P=0.003)。总体上，较高剂量的ITRE在防止临床恶化和实现临床改善方面显示出更大的益处。这些数据支持ILD导致的PH患者早期开始并上调治疗剂量，每天四次，至少9个基点。ClinicalTrials.gov；编号：NCT02630316；网址：www.Clinicaltrials.gov
Pulmonary hypertension (PH) complicates the course of many patients with fibrotic interstitial lung disease (ILD). Inhaled treprostinil (iTre) has been shown to improve functional ability and to delay clinical worsening in patients with PH resulting from ILD. Do higher dosages of iTre have greater benefits in preventing clinical worsening and achieving clinical improvement? Post hoc analysis of the INCREASE study, a 16-week double-blind, randomized, placebo-controlled trial of iTre in patients with PH resulting from ILD. Four groups were identified based on the number of breaths per session (bps; < 9 and ≥ 9 bps) of active drug or placebo attained at 4 weeks. Patients were evaluated for clinical worsening (15% decrease in 6-min walkdistance, cardiopulmonary hospitalization, lung transplantation, or death) or clinical improvement (15% increase in the six-minute walk distance with a concomitant 30% reduction in N-terminal prohormone of brain natriuretic peptide without any clinical worsening event). At 4 weeks, 70 patients were at a dose of ≥ 9 bps (high-dosage group) and 79 patients were at a dose of < 9 bps (low-dosage group) in the iTre arm vs 86 patients in the high-dose group and 67 patients in the low-dose group in the placebo arm. Between weeks 4 and 16, 17.1% of patients in the high-dose treprostinil group and 22.8% in the low-dose treatment group experienced a clinical worsening event vs 33.7% and 34.3% of patients in the two placebo arms, respectively (P = .006). By week 16, 15.7% and 12.7% of patients in the high- and low-dose iTre groups, respectively, demonstrated clinical improvement vs 7% and 1.5% patients in the placebo arms (P = .003) Higher dosages of iTre overall show greater benefit in terms of preventing clinical worsening and achieving clinical improvement. These data support the early initiation and uptitration of therapy to a dosage of at least 9 bps four times daily in patients with PH resulting from ILD. ClinicalTrials.gov; No.: NCT02630316; URL: www.clinicaltrials.gov
登录
查看更多内容
影响因子：
4.3
作者：
Nathan, Steven D.;du Bois, Roland M.;King, Talmadge E., Jr.
通讯作者：
King, Talmadge E., Jr.
DOI：
10.1164/rccm.201203-0480oc
发表时间：
2012-09-01
影响因子：
24.7
作者：
Mathai, Stephen C.;Puhan, Milo A.;Wise, Robert A.
通讯作者：
Wise, Robert A.
DOI：
10.1164/rccm.201403-0446oc
发表时间：
2014-07-15
影响因子：
24.7
作者：
Corte, Tamera J.;Keir, Gregory J.;Wort, Stephen J.
通讯作者：
Wort, Stephen J.
影响因子：
158.5
作者：
Waxman, Aaron;Restrepo-Jaramillo, Ricardo;Nathan, Steven D.
通讯作者：
Nathan, Steven D.
DOI：
10.1164/rccm.201007.1179oc
发表时间：
2011-05-01
影响因子：
24.7
作者：
du Bois, Roland M.;Weycker, Derek;King, Talmadge E., Jr.
通讯作者：
King, Talmadge E., Jr.