Advanced Lung Disease and Lung Transplant Program, Inova Fairfax Hospital, Falls Church, Virginia.
Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California.
Am J Respir Crit Care Med. 2022 Jan 15;205(2):198-207. doi: 10.1164/rccm.202107-1766OC.
The INCREASE study of inhaled treprostinil met its primary endpoint of change in 6-minute-walk distance at Week 16. In addition, there were significantly fewer clinical worsening events in patients receiving inhaled treprostinil. However, the incidence of multiple events in the same patient is unknown. This analysis evaluated the effect of continued treatment with inhaled treprostinil on the frequency and impact of multiple disease progression events. Patients enrolled in INCREASE were analyzed for disease progression events, defined as at least 15% decline in 6-minute-walk distance, exacerbation of underlying lung disease, cardiopulmonary hospitalization, lung transplantation, at least 10% decline in forced vital capacity, or death during the duration of the 16-week study. In total, 147 disease progression events occurred in the inhaled treprostinil group (89/163 patients, 55%) compared with 215 events (109/163 patients, 67%) in the placebo group ( = 0.018). There was a lower incidence of each disease progression component in the inhaled treprostinil group: 6-minute-walk distance decline (45 vs. 64 events), lung disease exacerbation (48 vs. 72 events), FVC decline (19 vs. 33), cardiopulmonary hospitalization (23 vs. 33 events), and death (10 vs. 12). Fewer patients receiving inhaled treprostinil had multiple progression events compared with those receiving the placebo (35 vs. 58, 22% vs. 36%; = 0.005). Patients who received inhaled treprostinil were significantly less likely to experience further disease progression events after an initial event compared with patients receiving placebo. These results support the continuation of inhaled treprostinil despite the occurrence of disease progression in clinical practice.
INCREASE 研究达到了其主要终点，即吸入曲前列尼尔治疗组患者在第 16 周时的 6 分钟步行距离改善。此外，吸入曲前列尼尔治疗组患者临床恶化事件明显减少。然而，同一患者中多个事件的发生率尚不清楚。本分析评估了持续接受吸入曲前列尼尔治疗对多种疾病进展事件的频率和影响。对 INCREASE 研究中的患者进行了疾病进展事件分析，定义为至少 15%的 6 分钟步行距离下降、基础肺部疾病恶化、心肺住院、肺移植、用力肺活量至少下降 10%或在 16 周研究期间死亡。在吸入曲前列尼尔组，共发生 147 例疾病进展事件（163 例患者中有 89 例，55%），而安慰剂组发生 215 例（163 例患者中有 109 例，67%）（ = 0.018）。吸入曲前列尼尔组的每个疾病进展组成部分的发生率较低：6 分钟步行距离下降（45 例与 64 例）、肺部疾病恶化（48 例与 72 例）、用力肺活量下降（19 例与 33 例）、心肺住院（23 例与 33 例）和死亡（10 例与 12 例）。与安慰剂组相比，接受吸入曲前列尼尔治疗的患者发生多种进展事件的人数较少（35 例与 58 例，22%与 36%； = 0.005）。与接受安慰剂的患者相比，接受吸入曲前列尼尔治疗的患者在发生初始事件后发生进一步疾病进展事件的可能性显著降低。这些结果支持在临床实践中继续使用吸入曲前列尼尔，尽管存在疾病进展。
