Fixed-dose combination therapy for Parkinson’s disease with a spotlight on entacapone in the past 20 years: a reduced pill burden and a simplified dosing regime

ABSTRACT

Introduction

Parkinson’s disease (PD) is a progressive, chronic neurodegenerative disorder. The main neuropathological cause of the disease is the death of dopaminergic neurons in the substantia nigra. Unfortunately, there is no curative treatment yet. The gold-standard of the treatment is levodopa (LD). During the course of the disease, motor complications develop, which postulates the addition of entacapone (ENT) to the dopaminergic medication. Previous studies have suggested that patients have a better quality of life when entacapone is added in a combination with LD.

Areas covered

A systematic literature search was performed. Articles were identified through PubMed (MEDLINE), Web of Science, Ovid, and ClinicalTrials.gov databases. The following search terms were used: ‘Levodopa’ AND ‘Carbidopa’ OR ‘Benserazide’ AND ‘Entacapone’. The search period was between 2000 and 2020. Twenty randomized and 10 non-randomized clinical trials (12,893 subjects) were included in the qualitative analysis. The systematic review was written in line with the PRISMA guideline.

Expert opinion

ENT administered in combination with LD resulted in a better quality of life compared to separate tablets. Therefore, in PD patients where impaired motor performance develops and the application of entacapone is necessary, it is suggested to be administered in a single tablet form.

KEYWORDS:

• Adherence
• combination
• entacapone
• fixed-dose
• non-motor symptoms
• Parkinson’s disease
• UPDRS

Article highlights

• Parkinson’s disease is the second most common neurodegenerative disorder with an estimated prevalence of around 10-18 persons per 100 000.

• The gold-standard of the treatment is levodopa (LD). However, during the course of the disease, motor complications develop which often leads the prescription of entacapone (ENT) in addition to the dopaminergic medication.

• ENT is a peripherally acting COMT-inhibitor.

• ENT administered in combination (LD/CD/ENT) results in a better quality of life compared to the drugs administered separately (LD/CD + ENT or LD/B + ENT)

• The cost-effectiveness of combination formulations may be an important future aspect for the patient’s and health insurance’s budget, especially as an increased QoL could increase a patient’s number of active years and reduce the need for hospital care.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work was supported by the Hungarian Brain Research Program (No. 2017-1.2.1-NKP-2017-00002_VI/4), the Hungarian National Research, Development and Innovation Office (NKFIH) through project GINOP 2.3.2-15-2016-00034 and The Ministry of Human Capacities, Hungary through grant TUDFO/47138-1/2019-ITM.