Journal Article

Effectiveness and safety of different catechol-o-methyl transferase inhibitors for patients with parkinson’s disease: Systematic review and network meta-analysis

Wu, Wenshuo, Hong, Du, Lu, Xiaohui, Zhang, Liping

2024

Overview

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. •We compared different COMT inhibitors with different dose through statistical analysis of 18 RCTs.•Opicapone (50 mg) as an adjuvant therapy for PD prolonged the total ON-time and decrease OFF-time of patients with PD.•Opicapone (50 mg) was less prone to adverse events.

• Publisher: Elsevier B.V,Elsevier Limited
• Subject: Adverse events / Antiparkinson Agents - adverse effects / Bias / Catechol / Catechol O-Methyltransferase Inhibitors - pharmacology / Catechol O-Methyltransferase Inhibitors - therapeutic use / Catechols - adverse effects / Clinical trials / COMT inhibitors / Dopamine / Dyskinesia / Handbooks / Humans / Levodopa / Levodopa - adverse effects / Meta-analysis / Movement disorders / Network meta-analysis / Neurodegenerative diseases / Neurology / Neurosurgery / Nitriles / Parkinson Disease - drug therapy / Parkinson's disease / Placebos / Randomized Controlled Trials as Topic / Software / Statistical analysis / Systematic review / Tolcapone / Tolcapone - therapeutic use / Transferases - therapeutic use