Inova Fairfax Hospital, Fall Church, VA.
United Therapeutics Corporation, Research Triangle Park, NC.
Chest. 2023 Feb;163(2):398-406. doi: 10.1016/j.chest.2022.09.007. Epub 2022 Sep 15.
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) INTERPRETATION: 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.
gov.
肺动脉高压（PH）使许多纤维化间质性肺疾病（ILD）患者的病情复杂化。吸入曲前列尼尔（iTre）已被证明可改善功能能力，并延缓 PH 患者的临床恶化。
较高剂量的 iTre 是否能更大程度地预防临床恶化并实现临床改善？
对 iTre 治疗 PH 患者的 INCREASE 研究进行了事后分析，这是一项为期 16 周的双盲、随机、安慰剂对照试验。根据 4 周时达到的每吸药物或安慰剂的呼吸次数（bps；<9 和≥9 bps），确定了 4 个组。评估患者是否发生临床恶化（6 分钟步行距离下降 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%，同时脑钠肽前体的 30%减少而无任何临床恶化事件）。
在第 4 周时，iTre 组中有 70 例患者的剂量为≥9 bps（高剂量组），79 例患者的剂量为<9 bps（低剂量组），而高剂量组中 86 例患者和低剂量组中 67 例患者在安慰剂组中接受治疗。在第 4 周到第 16 周之间，高剂量曲前列尼尔组中有 17.1%的患者和低剂量治疗组中有 22.8%的患者发生临床恶化事件，而安慰剂组中分别有 33.7%和 34.3%的患者发生临床恶化事件（P=0.006）。到第 16 周时，高剂量和低剂量 iTre 组中分别有 15.7%和 12.7%的患者表现出临床改善，而安慰剂组中分别有 7%和 1.5%的患者表现出临床改善（P=0.003）。
较高剂量的 iTre 总体上在预防临床恶化和实现临床改善方面具有更大的益处。这些数据支持在 PH 患者中尽早开始并滴定剂量至至少每天 4 次，每次 9 次 bps。
ClinicalTrials.gov；编号：NCT02630316；网址：www.clinicaltrials.gov。
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