Sood Namita, Aranda Alvaro, Platt David, LaRose Anneliese, Kleinjung Frank, O'Brien Gerald
1 McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA.
2 CardioPulmonary Research Center, San Juan, Puerto Rico.
Pulm Circ. 2019 Jan-Mar;9(1):2045894018823715. doi: 10.1177/2045894018823715. Epub 2018 Dec 21.
Pulmonary arterial hypertension (PAH) is characterized by progressive dyspnea and exercise limitation and is associated with reduced health-related quality of life. Few clinical studies have evaluated the primary effects of treatment of PAH from the patient perspective. Here, we present the impact of riociguat on patient-reported outcomes (PROs) in treatment-naïve patients with PAH. MOTION (NCT02191137) was an open-label, phase 4 trial of riociguat monotherapy in treatment-naïve patients with PAH. The primary endpoint was the change in total score from baseline to Week 24 in the Living with Pulmonary Hypertension (LPH) questionnaire. The Short Form-12 Health Survey and Work Limitations Questionnaire 8 were also utilized to assess PROs. Other secondary endpoints included change from baseline in World Health Organization functional class (WHO FC), 6-min walk distance (6MWD), Modified Borg Dyspnea Scale, and safety. At week 24 (n = 66), the mean (standard deviation [SD]) total LPH score was 37.17 (24.61), for a mean (SD) change from baseline of -10.99 (22.51). At last visit, with week 24 imputed, the mean (SD) total score was 40.63 (28.38), for a mean (SD) change from baseline of -5.40 (27.8) (n = 75; P = 0.0484). Improvement in LPH questionnaire total score was observed by week 4 and was maintained through week 24. Improvements were observed in WHO FC, Modified Borg Dyspnea Scale, and accelerometer-measured 6MWD at week 24. Treatment with riociguat had a positive impact on PROs in treatment-naïve patients with PAH and was well tolerated, with a similar safety profile to that observed in placebo-controlled phase 3 trials.
肺动脉高压(PAH)的特征是进行性呼吸困难和运动受限,并与健康相关生活质量下降有关。很少有临床研究从患者角度评估PAH治疗的主要效果。在此,我们展示了利奥西呱对初治PAH患者报告结局(PROs)的影响。MOTION(NCT02191137)是一项在初治PAH患者中进行的利奥西呱单药治疗的开放标签4期试验。主要终点是肺动脉高压生存(LPH)问卷中从基线到第24周的总分变化。还使用了简短健康调查问卷12和工作限制问卷8来评估PROs。其他次要终点包括世界卫生组织功能分级(WHO FC)、6分钟步行距离(6MWD)、改良Borg呼吸困难量表的基线变化以及安全性。在第24周(n = 66)时,LPH总分的平均值(标准差[SD])为37.17(24.61),相对于基线的平均(SD)变化为 -10.99(22.51)。在末次访视时,推算第24周的数据,总分的平均值(SD)为40.63(28.38),相对于基线的平均(SD)变化为 -5.40(27.8)(n = 75;P = 0.0484)。在第4周时观察到LPH问卷总分有所改善,并持续到第24周。在第24周时,WHO FC、改良Borg呼吸困难量表以及加速度计测量的6MWD均有改善。利奥西呱治疗对初治PAH患者的PROs有积极影响,且耐受性良好,其安全性与安慰剂对照3期试验中观察到的相似。