Chung Sun Ju, Calopa Matilde, Ceravolo Maria G, Tambasco Nicola, Antonini Angelo, Chaudhuri K Ray, Robieson Weining Z, Sánchez-Soliño Olga, Zadikoff Cindy, Jin Man, Barbato Luigi M
Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Department of Neurology, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain.
Parkinsons Dis. 2022 Nov 4;2022:1216975. doi: 10.1155/2022/1216975. eCollection 2022.
Nonmotor symptoms (NMS) are common in advanced Parkinson's disease (APD) and reduce health-related quality of life.
The aim of the study was to evaluate levodopa-carbidopa intestinal gel (LCIG) versus optimized medical treatment (OMT) on NMS in APD.
INSIGHTS was a phase 3b, open-label, randomized, multicenter study in patients with APD (LCIG or OMT, 26 weeks) (NCT02549092). Primary outcomes assessed were total NMS (NMS scale (NMSS) and PD sleep scale (PDSS-2)). Key secondary outcomes included the Unified PD Rating Scale (UPDRS) Part II, Clinical Global Impression of Change (CGI-C), and PD Questionnaire-8 (PDQ-8). Additional secondary measures of Patient Global Impression of Change (PGIC), King's PD Pain Scale (KPPS), and Parkinson Anxiety Scale (PAS) also were evaluated. Finally, safety was assessed.
Out of 89 patients randomized, 87 were included in the analysis (LCIG, = 43; OMT, = 44). There were no significant differences in NMSS or PDSS-2 total score changes (baseline to Week 26) between LCIG and OMT; within-group changes were significant for NMSS (LCIG, < 0.001; OMT, = 0.005) and PDSS-2 (LCIG, < 0.001; OMT, < 0.001). Between-group treatment differences were nominally significant for UPDRS Part II ( = 0.006) and CGI-C ( < 0.001) at Week 26 in favor of LCIG; however, statistical significance could not be claimed in light of primary efficacy outcomes. PGIC (Week 26) and KPPS (Week 12) scores were nominally significantly reduced with LCIG versus OMT ( < 0.001; < 0.05). There were no significant differences in PDQ-8 or PAS. Adverse events (AEs) were mostly mild to moderate; common serious AEs were pneumoperitoneum ( = 2) and stoma-site infection ( = 2) (LCIG).
There were no significant differences between LCIG versus OMT in NMSS or PDSS-2; both LCIG and OMT groups significantly improved from baseline. AEs were consistent with the known safety profile.
非运动症状（NMS）在晚期帕金森病（APD）中很常见，会降低与健康相关的生活质量。
本研究旨在评估左旋多巴-卡比多巴肠凝胶（LCIG）与优化药物治疗（OMT）对APD患者非运动症状的影响。
INSIGHTS是一项3b期、开放标签、随机、多中心研究，纳入APD患者（LCIG或OMT治疗，为期26周）（NCT02549092）。评估的主要结局为总的非运动症状（非运动症状量表（NMSS）和帕金森病睡眠量表（PDSS-2））。关键次要结局包括统一帕金森病评定量表（UPDRS）第二部分、临床总体印象变化量表（CGI-C）和帕金森病问卷-8（PDQ-8）。还评估了患者总体印象变化量表（PGIC）、国王帕金森病疼痛量表（KPPS）和帕金森焦虑量表（PAS）等其他次要指标。最后，评估安全性。
89例随机分组患者中，87例纳入分析（LCIG组43例；OMT组44例）。LCIG组和OMT组之间，NMSS或PDSS-2总分变化（基线至第26周）无显著差异；组内NMSS（LCIG组，<0.001；OMT组，=0.005）和PDSS-2（LCIG组，<0.001；OMT组，<0.001）变化显著。第26周时，UPDRS第二部分（=0.006）和CGI-C（<0.001）组间治疗差异名义上显著，LCIG组更优；然而，鉴于主要疗效结局，无法宣称具有统计学意义。与OMT组相比，LCIG组PGIC（第26周）和KPPS（第12周）评分名义上显著降低（<0.001；<0.05）。PDQ-8或PAS无显著差异。不良事件（AE）大多为轻度至中度；常见严重AE为气腹（=2）和造口部位感染（=2）（LCIG组）。
LCIG组和OMT组在NMSS或PDSS-2方面无显著差异；LCIG组和OMT组均较基线有显著改善。不良事件与已知安全性特征一致。
