Incidence of Adverse and Safety Events in Individuals with Parkinson’s Disease Treated with Catechol-O-Methyltransferase Inhibitor Opicapone as an Add-On to Levodopa Treatment: A Systematic Review and Meta-Analysis

Paula Abola; George Jabishvili

doi:10.56782/pps.563

Published : 2025-08-13

No. 2025 (Early Access)

Incidence of Adverse and Safety Events in Individuals with Parkinson’s Disease Treated with Catechol-O-Methyltransferase Inhibitor Opicapone as an Add-On to Levodopa Treatment: A Systematic Review and Meta-Analysis

Paula Abola

George Jabishvili

DOI: https://doi.org/10.56782/pps.563

Abstract

Opicapone, a once-daily catechol-O-methyltransferase (COMT) inhibitor, is used as an add-on to levodopa treatment to manage motor fluctuations in Parkinson’s Disease (PD). Although its efficacy in extending ON time is established, the safety profile of opicapone, particularly regarding adverse events and dyskinesia, remains under investigation. A systematic review and meta-analysis were performed with randomized controlled trials (RCTs) and open-label trials that investigated the incidence of adverse events in individuals with PD treated with opicapone as an add-on to levodopa treatment. The systematic search was conducted in PubMed, Cochrane, and EBSCO Megafile databases. Random-effects meta-analyses calculated risk ratios (RR) for adverse events, serious adverse events, adverse events leading to discontinuation, and dyskinesia. Certainty of evidence was assessed using the Cochrane Grading Recommendations Assessment, Development and Evaluation approach. Six studies (n = 2705) were included, with four RCTs eligible for meta-analysis. Opicapone at both 25 mg and 50 mg doses was associated with a significantly increased risk of dyskinesia compared to placebo (25 mg: RR = 2.47; 50 mg: RR = 2.75). No statistically significant differences were found for overall adverse events, serious adverse events, or adverse events leading to discontinuation. Heterogeneity across studies was generally low. Opicapone, as an add-on to levodopa treatment, shows a favorable overall safety profile, with the primary concern being an increased incidence of dyskinesia. Clinicians should monitor for motor complications and adjust levodopa dosing as needed. Further research is needed to refine dyskinesia management strategies and evaluate long-term safety outcomes.

Keywords:

Parkinson’s Disease, Opicapone, adverse events, safety events

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Abola, P., & Jabishvili, G. (2025). Incidence of Adverse and Safety Events in Individuals with Parkinson’s Disease Treated with Catechol-O-Methyltransferase Inhibitor Opicapone as an Add-On to Levodopa Treatment: A Systematic Review and Meta-Analysis. Prospects in Pharmaceutical Sciences, (2025 (Early Access). https://doi.org/10.56782/pps.563

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References

1. Greenwood J, Pham H, Rey J. opicapone: A third generation COMT inhibitor. Clinical Parkinsonism & Related Disorders. 2021;4:100083. doi:https://doi.org/10.1016/j.prdoa.2020.100083

2. Antonini A, Barone P, Calabresi P, et al. The role of opicapone in the management of Parkinson’s disease: an Italian consensus through a combined Nominal Group Technique and Delphi approach. European review for medical and pharmacological sciences. 2023;27(18):8850-8859. doi:https://doi.org/10.26355/eurrev_202309_33805

3. Ferreira JJ, Lee JY, Ma HI, et al. opicapone for the treatment of early wearing-off in levodopa-treated Parkinson’s disease: pooled analysis of patient level data from two randomized open-label studies. Journal of neurology. 2024;271(10):6729-6738. doi:https://doi.org/10.1007/s00415-024-12614-8

4. Ferreira JJ, Lees A, Rocha JF, Poewe W, Rascol O, Soares-da-Silva P. opicapone as an adjunct to levodopa in patients with Parkinson’s disease and end-of-dose motor fluctuations: a randomised, double-blind, controlled trial. The Lancet Neurology. 2016;15(2):154-165. doi:https://doi.org/10.1016/s1474-4422(15)00336-1

5. Lees AJ, Ferreira J, Rascol O, et al. opicapone as Adjunct to levodopa Therapy in Patients With Parkinson Disease and Motor Fluctuations. JAMA Neurology. 2017;74(2):197. doi:https://doi.org/10.1001/jamaneurol.2016.4703

6. Ferreira JJ, Lees AJ, Poewe W, et al. Effectiveness of opicapone and switching from entacapone in fluctuating Parkinson disease. Neurology. 2018;90(21). doi:https://doi.org/10.1212/wnl.0000000000005557

7. Takeda A, Takahashi R, Tsuboi Y, et al. Randomized, Controlled Study of opicapone in Japanese Parkinson’s Patients with Motor Fluctuations. Movement Disorders. 2020;36(2):415-423. doi:https://doi.org/10.1002/mds.28322

8. Takeda A, Takahashi R, Tsuboi Y, et al. Long-term safety and efficacy of opicapone in Japanese Parkinson’s patients with motor fluctuations. Journal of Neural Transmission. 2021;128(3):337-344. doi:https://doi.org/10.1007/s00702-021-02315-1

9. Ferreira JJ, Rascol O, Stocchi F, et al. opicapone as adjunct to levodopa in treated Parkinson’s disease without motor complications: A randomized clinical trial. European Journal of Neurology. 2025;32(1). doi:https://doi.org/10.1111/ene.16420

10. Xie L, Qi X, Wang X, et al. Adverse event profiles of adjuvant treatment with opicapone in Parkinson’s disease: A systematic review and meta-analysis. Frontiers in Pharmacology. 2022;13. doi:https://doi.org/10.3389/fphar.2022.1042992

11. Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. British Medical Journal. 2021;372(71). doi:https://doi.org/10.1136/bmj.n71

12. Palmer R, Dimairo M, Latimer N, et al. Definitions of adverse events and serious adverse events and categories of serious adverse event results. www.ncbi.nlm.nih.gov. Published April 1, 2020. Accessed May 23, 2024. https://www.ncbi.nlm.nih.gov/books/NBK556726/

13. Fabbrini G, Brotchie JM, Grandas F, Nomoto M, Goetz CG. levodopa‐induced dyskinesias. Movement Disorders. 2007;22(10):1379-1389. doi:https://doi.org/10.1002/mds.21475

14. Clarke CE, Smitaa Patel, Ives N, et al. UK Parkinson’s Disease Society Brain Bank Diagnostic Criteria. Nih.gov. Published August 2016. https://www.ncbi.nlm.nih.gov/books/NBK379754/

15. Sterne JAC, Savović J, Page MJ, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366(1):l4898. doi:https://doi.org/10.1136/bmj.l4898

16. Cochrane. 9.5.2 Identifying and measuring heterogeneity. Cochrane.org. Published 2019. https://handbook-5-1.cochrane.org/chapter_9/9_5_2_identifying_and_measuring_heterogeneity.htm

17. Cochrane. 10.4.3.1 Recommendations on testing for funnel plot asymmetry. Cochrane.org. Published 2019. https://handbook-5-1.cochrane.org/chapter_10/10_4_3_1_recommendations_on_testing_for_funnel_plot_asymmetry.htm

18. Zeng L, Brignardello-Petersen R, Hultcrantz M, et al. GRADE guidelines 32: GRADE offers guidance on choosing targets of GRADE certainty of evidence ratings. Journal of Clinical Epidemiology. 2021;137:163-175. doi:https://doi.org/10.1016/j.jclinepi.2021.03.026

19. Regensburger M, Chi Wang Ip, Kohl Z, et al. Clinical benefit of MAO-B and COMT inhibition in Parkinson’s disease: practical considerations. Journal of Neural Transmission. 2023;130(6):847-861. doi:https://doi.org/10.1007/s00702-023-02623-8

Paula Abola

paula.abola@uj.edu

Affiliation:

a:1:{s:5:"en_US";s:23:"University of Jamestown";} United States

George Jabishvili

Affiliation:

FIECON United Kingdom