Zhejiang Chinese Medical University, 548th Binwen Road, Hangzhou 310053, PR China.
The First School of Medicine, Zhejiang Chinese Medical University, 548th Binwen Road, Hangzhou 310053, PR China.
Clin Neurol Neurosurg. 2024 Apr;239:108189. doi: 10.1016/j.clineuro.2024.108189. Epub 2024 Feb 23.
Levodopa treatment requires the addition of other drugs, such as catechol-O-methyl transferase (COMT) inhibitors, to alleviate motor fluctuations in advanced parkinson's disease (PD). However, the optimal strategy, including the type and dose of COMT inhibitors remains unknown. This systematic review and network meta-analysis aimed to assess the efficacy and safety of different COMT inhibitors and for treating PD patients.
PubMed, Embase, Cochrane Library and Web of Science were screened up to November 20, 2022. Randomized controlled trials (RCTs) of COMT inhibitors (entacapone, opicapone, tolcapone) for PD patients were included. Eligible outcomes were total ON-time, rate of ON-time >1 h, total daily dose of levodopa therapy, mean change from baseline to final follow up in Unified Parkinson's Disease Rating Scale (UPDRS) part III scores, adverse events and dyskinesia. Network meta-analyses integrated direct and indirect evidence with placebo as a common comparator.
We identified 18 studies with 7564 patients. Opicapone, entacapone, and tolcapone could increase total ON-time when compared with placebo. However, opicapone (25 mg, MD 4.0, 95%CrI: 1.1-7.5) and opicapone (50 mg, MD 5.1, 95%CrI: 2.2-8.7) statistically significant increase the total ON-time. opicapone and entacapone could increase the rate of ON-time >1 h when compared with placebo. Only opicapone (5 mg) showed no statistically significant with placebo (OR 1.4, 95%CrI: 0.74-2.4). We found that opicapone (50 mg, SURCA, 0.796) is the best option compared with other treatments. TOL (200 mg) was ranked highest in the rank probability test for total daily dose of levodopa therapy, followed by OPI (50 mg), TOL (400 mg) and TOL (100 mg) in order. SUCRA rankings identified TOL (200 mg) as the most likely therapy for increasing adverse events (SUCRA 27.19%), followed by TOL (400 mg, SUCRA 27.20%) and OPI (5 mg, SUCRA 30.81%). The SUCRA probabilities were 91.6%, 75.2%, 67.9%, 59.3%, 45.6%, 41.1%, 35.1%, 24.6% and 9.4% for PLA, TOL (400 mg), ENT (100 mg), ENT (200 mg), OPI (5 mg), TOL (100 mg), OPI (25 mg), OPI (50 mg), and TOL (200 mg) respectively.
In conclusion, opicapone (50 mg) may be a better choice for treatment PD when compared with other COMT inhibitors.
左旋多巴治疗需要添加其他药物，如儿茶酚-O-甲基转移酶（COMT）抑制剂，以缓解晚期帕金森病（PD）的运动波动。然而，最佳策略，包括 COMT 抑制剂的类型和剂量，仍不清楚。本系统评价和网络荟萃分析旨在评估不同 COMT 抑制剂治疗 PD 患者的疗效和安全性。
截至 2022 年 11 月 20 日，我们在 PubMed、Embase、Cochrane 图书馆和 Web of Science 上进行了筛选。纳入了 COMT 抑制剂（恩他卡朋、奥匹卡朋、托卡朋）治疗 PD 患者的随机对照试验（RCT）。纳入的结局指标包括总开期时间、开期时间＞1 h 的比例、左旋多巴治疗的总日剂量、统一帕金森病评定量表（UPDRS）第三部分评分从基线到最终随访的平均变化、不良事件和运动障碍。网络荟萃分析整合了直接和间接证据，并将安慰剂作为共同比较剂。
我们共纳入了 18 项研究，涉及 7564 名患者。与安慰剂相比，奥匹卡朋、恩他卡朋和托卡朋均可增加总开期时间。然而，奥匹卡朋（25mg，MD 4.0，95%CrI：1.1-7.5）和奥匹卡朋（50mg，MD 5.1，95%CrI：2.2-8.7）显著增加了总开期时间。奥匹卡朋和恩他卡朋可增加开期时间＞1 h 的比例。与安慰剂相比，只有奥匹卡朋（5mg）没有统计学意义（OR 1.4，95%CrI：0.74-2.4）。我们发现，与其他治疗相比，奥匹卡朋（50mg，SURCA，0.796）是最佳选择。TOL（200mg）在总左旋多巴治疗日剂量的秩概率检验中排名最高，其次是 OPI（50mg）、TOL（400mg）和 TOL（100mg）。SUCRA 排名确定 TOL（200mg）为增加不良事件的最可能治疗方法（SUCRA 27.19%），其次是 TOL（400mg，SUCRA 27.20%）和 OPI（5mg，SUCRA 30.81%）。PLA、TOL（400mg）、ENT（100mg）、ENT（200mg）、OPI（5mg）、TOL（100mg）、OPI（25mg）、OPI（50mg）和 TOL（200mg）的 SUCRA 概率分别为 91.6%、75.2%、67.9%、59.3%、45.6%、41.1%、35.1%、24.6%和 9.4%。
综上所述，与其他 COMT 抑制剂相比，奥匹卡朋（50mg）可能是治疗 PD 的更好选择。
