Ruan Xinglin, Lin Fabin, Wu Dihang, Chen Lina, Weng Huidan, Yu Jiao, Wang Yingqing, Chen Ying, Chen Xiaochun, Ye Qinyong, Meng Fangang, Cai Guoen
Department of Neurology, Fujian Medical University Union Hospital, Fujian, China.
Department of Clinical Medicine, Fujian Medical University, Fujian, China.
Front Neurosci. 2021 Oct 29;15:728083. doi: 10.3389/fnins.2021.728083. eCollection 2021.
Movement fluctuations are the main complication of Parkinson's disease (PD) patients receiving long-term levodopa (L-dopa) treatment. We compared and ranked the efficacy and safety of dopamine agonists (DAs) with regard to motor fluctuations by using a Bayesian network meta-analysis (NMA) to quantify information from randomized controlled trials (RCTs). We carried out a systematic review and meta-analysis, and only RCTs comparing DAs for advanced PD were included. Electronic databases (PubMed, Embase, and Cochrane Library) were systematically searched for relevant studies published until January 2021. Two reviewers independently extracted individual study data and evaluated studies for risk of bias using the Cochrane Risk of Bias tool. Network meta-analyses using a Bayesian framework were used to calculate the related parameters. The pre-specified primary and secondary outcomes were efficacy ("ON" time without troublesome dyskinesia, "OFF" time, "ON" time, "UPDRS-III," and "UPDRS-II") and safety [treatment-emergent adverse events (TEAE) and other adverse events] of DAs. The results are presented as the surface under the cumulative ranking (SUCRA) curve. A total of 20 RCTs assessing 6,560 patients were included. The general DA effects were ranked from high to low with respect to the amount of "ON" time without troublesome dyskinesia as follows: apomorphine (SUCRA = 97.08%), pramipexole_IR (probability = 79.00%), and ropinirole_PR (SUCRA = 63.92%). The general safety of DAs was ranked from high to low with respect to TEAE as follows: placebo (SUCRA = 74.49%), pramipexole_ER (SUCRA = 63.6%), sumanirole (SUCRA = 54.07%), and rotigotine (SUCRA = 53.84%). This network meta-analysis shows that apomorphine increased "ON" time without troublesome dyskinesia and decreased "OF" time for advanced PD patients. The addition of pramipexole, ropinirole, or rotigotine to levodopa treatment in advanced PD patients with motor fluctuations increased "ON" time without troublesome dyskinesia, improved the UPDRS III scores, and ultimately ameliorated the UPDRS II scores, thereby maximizing its benefit. This NMA of pramipexole, ropinirole, and rotigotine represents an effective treatment option and has an acceptable safety profile in patients with advanced PD.
运动波动是帕金森病（PD）患者长期接受左旋多巴（L - 多巴）治疗的主要并发症。我们通过使用贝叶斯网络荟萃分析（NMA）来量化随机对照试验（RCT）中的信息，比较并排序了多巴胺激动剂（DAs）在运动波动方面的疗效和安全性。我们进行了一项系统评价和荟萃分析，仅纳入了比较DAs用于晚期PD的RCT。系统检索电子数据库（PubMed、Embase和Cochrane图书馆）中截至2021年1月发表的相关研究。两名评价者独立提取个体研究数据，并使用Cochrane偏倚风险工具评估研究的偏倚风险。使用贝叶斯框架的网络荟萃分析用于计算相关参数。预先设定的主要和次要结局是DAs的疗效（无麻烦异动症的“开”期时间、“关”期时间、“开”期时间、“统一帕金森病评定量表第三部分”[UPDRS - III]和“统一帕金森病评定量表第二部分”[UPDRS - II]）和安全性[治疗中出现的不良事件（TEAE）和其他不良事件]。结果以累积排序曲线下面积（SUCRA）表示。共纳入20项评估6560例患者的RCT。就无麻烦异动症的“开”期时间而言，DAs的总体疗效从高到低排序如下：阿扑吗啡（SUCRA = 97.08%）、普拉克索速释片（概率 = 79.00%）和罗匹尼罗缓释片（SUCRA = 63.92%）。就TEAE而言，DAs的总体安全性从高到低排序如下：安慰剂（SUCRA = 74.49%）、普拉克索缓释片（SUCRA = 63.6%）、舒马曲坦（SUCRA = 54.07%）和罗替戈汀（SUCRA = 53.84%）。这项网络荟萃分析表明，阿扑吗啡增加了晚期PD患者无麻烦异动症的“开”期时间并减少了“关”期时间。在有运动波动的晚期PD患者中，在左旋多巴治疗中添加普拉克索、罗匹尼罗或罗替戈汀可增加无麻烦异动症的“开”期时间，改善UPDRS III评分，并最终改善UPDRS II评分，从而使其获益最大化。这项对普拉克索、罗匹尼罗和罗替戈汀的NMA代表了一种有效的治疗选择，并且在晚期PD患者中具有可接受的安全性。
