Different Catechol-O-Methyl Transferase Inhibitors in Parkinson's Disease: A Bayesian Network Meta-Analysis

Abstract

Parkinson's disease (PD) is a common, chronic, progressive, debilitating neurodegenerative disease. The current levodopa treatment requires the addition of other drugs, such as catechol-O-methyl transferase (COMT) inhibitors, to alleviate motor fluctuations in advanced PD. Therefore, a theoretical reference for treatment is urgently needed. In this study, an appropriate search strategy was used to screen eligible studies on different drugs to treat patients with PD from the Embase, PubMed, and Cochrane Library. The publication dates were from January 1990 to June 2021. We integrated eligible randomized controlled trials, and statistical analysis was performed on three kinds of effectiveness outcomes and two types of safety outcomes. We assessed the average difference or odds ratio between each drug and placebo and summarized them as the average and 95% confidence interval (CI), respectively. In terms of efficacy, entacapone (mean difference [MD], 0.64 h; 95% CI, 0.29–1.0), opicapone (MD, 0.92 h; 95% CI, 0.35–1.5), and tolcapone (MD, 3.2 h; 95% CI, 2.1–4.2) increased patients' total ON-time compared to placebo. Tolcapone (MD, −100 mg; 95% CI −160 to −45) reduced the total daily dose of levodopa therapy. None of these three drugs was found to have statistical significance in mean change from baseline in UPDRS part III scores when compared with others. In terms of safety, tolcapone (MD, 3.8; 95% CI, 2.1–6.8), opicapone (MD, 3.7; 95% CI, 2–7.2), and entacapone (MD, 2.2; 95% CI, 1.5–3.3) increased the number of cases of dyskinesia compared to placebo. Entacapone (MD, 1.7; 95% CI, 1.3–2.2) and tolcapone (MD, 4.3; 95% CI, 1.3–15) were more likely to cause adverse events than placebo. In conclusion, opicapone showed higher efficiency and fewer safety problems in five indicators we selected when compared with the other two drugs.

Efficacy and Safety of Opicapone for Motor Fluctuations as an Adjuvant to Levodopa Therapy in Patients with Parkinson’s Disease: A Systematic Review and Meta-Analysis

“…However, tolcapone has safety concerns owing to fulminant hepatotoxicity [ 31, 32 ]; thus, entacapone is currently more widely used than tolcapone in patients with advanced PD [ 33 ]. Another recent network meta-analysis showed that opicapone and entacapone were slightly inferior to tolcapone in on-time increase; however, the main outcomes of the present study, including off-time reduction and on-time increase without troublesome dyskinesia, were not analyzed [ 34 ]. According to the BIPARK-I trial, the reduction in off-time was higher in the opicapone 50 mg group (–116.8 min) than in the entacapone 200 mg group (–96.3 min) [ 8 ].…”

The recent guidelines for pharmacotherapy of Parkinson’s Disease

“…Chronic use of L-DOPA leads to certain non-motor symptoms, like L-DOPA-induced-dyskinesia (LID), motor fluctuations, including early-morning off (lack of the efficiency of drug after wake up), wearing-off (reduction of duration of action), delayed-on (delay of drug action), no-on (dose-failure, lack of effect after drug dosage), and on-off phenomena (ON-time, in which the symptoms are under control and the patient can move without difficulty versus the sudden appearance of OFF-time, when the patient is immobile). The mechanism for this is still unclear [2][3][4][5][6].…”

Evaluating Opicapone as Add-on Treatment to Levodopa/DDCI in Patients with Parkinson’s Disease

“…Opicapone combines several advantages: Its potency is similar to that of tolcapone, 6 it only needs to be taken once daily and it provides long-lasting COMT-inhibition due to the high binding affinity and a slow dissociation rate of the opicapone-COMT-complex. After 24 h, COMT activity is only reduced by approx.…”

“… 8 A recent meta-analysis concluded that opicapone is superior to both entacapone and tolcapone in terms of efficacy and safety. 6 …”