Abstract：
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.
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.
摘要：
背景：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，缓解晚期帕金森病（PD）的运动波动。然而,最优策略，包括COMT抑制剂的类型和剂量仍然未知.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。
方法：PubMed，Embase,Cochrane图书馆和WebofScience在2022年11月20日之前进行了筛选。COMT抑制剂（entacapone，opicapone,包括PD患者的托卡朋）。合格的结果是总的ON时间，导通时间>1小时的速率，左旋多巴治疗的每日总剂量，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。网络荟萃分析将直接和间接证据与安慰剂作为常见的比较物相结合。
结果：我们确定了18项研究，包括7564名患者。Opicapone,entacapone,与安慰剂相比，托卡朋可以增加总ON时间。然而,opicapone（25毫克，MD4.0，95％CrI：1.1-7.5）和opicapone（50mg，MD5.1，95％CrI：2.2-8.7）统计学上显着增加总ON时间。与安慰剂相比，opicapone和entacapone可以增加ON时间>1h的速率。只有opicapone（5mg）与安慰剂没有统计学意义（OR1.4，95％CrI：0.74-2.4）。我们发现opicapone(50毫克，SURCA,0.796）是与其他治疗方法相比的最佳选择。TOL（200mg）在左旋多巴治疗总每日剂量的等级概率检验中排名最高，其次是OPI（50毫克），TOL(400mg)和TOL(100mg)依次为。SUCRA排名确定TOL（200mg）是最可能增加不良事件的治疗方法（SUCRA27.19％），其次是TOL(400毫克，SUCRA27.20%)和OPI(5毫克，SUCRA30.81%）。SUCRA概率为91.6%，75.2%,67.9%,59.3%,45.6%,41.1%,35.1%,PLA的24.6%和9.4%，TOL(400mg),ENT(100mg),ENT(200mg),OPI（5毫克），TOL(100mg),OPI（25毫克），OPI（50毫克），和TOL(200mg)。
结论：结论：与其他COMT抑制剂相比，opicapone（50mg）可能是治疗PD的更好选择。
方法：PubMed，Embase,Cochrane图书馆和WebofScience在2022年11月20日之前进行了筛选。COMT抑制剂（entacapone，opicapone,包括PD患者的托卡朋）。合格的结果是总的ON时间，导通时间>1小时的速率，左旋多巴治疗的每日总剂量，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。网络荟萃分析将直接和间接证据与安慰剂作为常见的比较物相结合。
结果：我们确定了18项研究，包括7564名患者。Opicapone,entacapone,与安慰剂相比，托卡朋可以增加总ON时间。然而,opicapone（25毫克，MD4.0，95％CrI：1.1-7.5）和opicapone（50mg，MD5.1，95％CrI：2.2-8.7）统计学上显着增加总ON时间。与安慰剂相比，opicapone和entacapone可以增加ON时间>1h的速率。只有opicapone（5mg）与安慰剂没有统计学意义（OR1.4，95％CrI：0.74-2.4）。我们发现opicapone(50毫克，SURCA,0.796）是与其他治疗方法相比的最佳选择。TOL（200mg）在左旋多巴治疗总每日剂量的等级概率检验中排名最高，其次是OPI（50毫克），TOL(400mg)和TOL(100mg)依次为。SUCRA排名确定TOL（200mg）是最可能增加不良事件的治疗方法（SUCRA27.19％），其次是TOL(400毫克，SUCRA27.20%)和OPI(5毫克，SUCRA30.81%）。SUCRA概率为91.6%，75.2%,67.9%,59.3%,45.6%,41.1%,35.1%,PLA的24.6%和9.4%，TOL(400mg),ENT(100mg),ENT(200mg),OPI（5毫克），TOL(100mg),OPI（25毫克），OPI（50毫克），和TOL(200mg)。
结论：结论：与其他COMT抑制剂相比，opicapone（50mg）可能是治疗PD的更好选择。
