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
DOI:
https://doi.org/10.56782/pps.563Keywords:
Parkinson’s Disease, Opicapone, adverse events, safety eventsAbstract
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 on 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 of 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.
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1. Greenwood, J.; Pham, H.; Rey, J. Opicapone: A third generation COMT inhibitor. Clin. Park. Relat. Disord. 2020, 4, Art. No: 100083. DOI: 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. Eur. Rev. Med. Pharmacol. Sci. 2023, 27(18), 8850-8859. DOI: 10.26355/eurrev_202309_33805
3. Ferreira, J.J.; Lee, J.Y.; Ma, H.I.; 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. J. Neurol. 2024, 271(10), 6729-6738. DOI: 10.1007/s00415-024-12614-8
4. Ferreira, J.J.; Lees, A.; Rocha J.F.; 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 Neurol. 2016, 15(2), 154-165. DOI: 10.1016/s1474-4422(15)00336-1
5. Lees A.J.; Ferreira, J.J.; Rascol O.; et al. Opicapone as Adjunct to levodopa Therapy in Patients With Parkinson Disease and Motor Fluctuations. JAMA Neurol. 2017, 74(2), 197-206. DOI: 10.1001/jamaneurol.2016.4703
6. Ferreira, J.J.; Lees A.J.; Poewe W.; et al. Effectiveness of opicapone and switching from entacapone in fluctuating Parkinson disease. Neurology 2018, 90(21), e1849-e1857. DOI: 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. Mov. Disord. 2020, 36(2), 415-423. DOI: 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. J. Neural Transm. 2021, 128(3), 337-344. DOI: 10.1007/s00702-021-02315-1
9. Ferreira, J.J.;, Rascol, O.; Stocchi, F.; et al. Opicapone as adjunct to levodopa in treated Parkinson’s disease without motor complications: A randomized clinical trial. Eur. J. Neurol. 2025, 32(1), Art. No: e16420. DOI: 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. Front. Pharmacol. 2022, 13, Art. No: 1042992. DOI: 10.3389/fphar.2022.1042992
11. Page, M.J.; McKenzie, J.E.; Bossuyt, P.M.; et al. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. BMJ 2021, 372, Art. No: n71. DOI: 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, J.M.; Grandas, F.; Nomoto, M.; Goetz, C.G. Levodopa‐induced dyskinesias. Mov. Disord. 2007, 22(10), 1379-1389. DOI: 10.1002/mds.21475
14. Clarke, C.E.; 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, J.A.C.; Savović, J.; Page, M.J.; et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ 2019, 366(1), Art. No: l4898. DOI: 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. J. Clin. Epidemiol. 2021, 137, 163-175. DOI: 10.1016/j.jclinepi.2021.03.026
19. Regensburger, M.; Ip, C.W.; Kohl, Z.; et al. Clinical benefit of MAO-B and COMT inhibition in Parkinson’s disease: practical considerations. J. Neural Transm. 2023, 130(6), 847-861. DOI: 10.1007/s00702-023-02623-8
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