Objective: To identify genetic variants associated with different clinical responses in patients with Parkinson’s disease(PD) treated with opicapone.

Background: Opicapone is a catechol‐O‐methyltransferase(COMT) inhibitor used as adjunct to levodopa(LD) therapy in patients with PD and motor fluctuations. It has been shown to reduce “off” time with few adverse events(AE) and to improve their quality of life[1][2][3]. There is little data regarding the effect of genetic variants of genetic variants in the COMT and UGT1A genes on opicapone response[4][5].

Method: A retrospective study was performed including PD patients treated with opicapone between May of 2017 to November of 2021 from our Movement Disorders Unit.

Clinical data was collected from the first visit after opicapone prescription. Clinical response, including change in motor fluctuations and dyskinesias (classified as improvement, stability or worsening), the Clinical Global Impression (CGI) score and the AE development were analyzed. We genotyped rs4818, rs4680, rs4633 in the COMT gene and rs1105880 in the UGT1A gene using Taqman probes. Binomial and ordinal logistic regression analyses were used to correlate clinical variables with the genotype.

Results: We included 171 patients(58,4% male, mean age 63±12 years; with a mean disease duration 12±7years). According to the dominant inheritance model for rs4680, the genotype associated with low o intermediate activity in the COMT enzyme seemed to act as a protective factor against the worsening of motor fluctuations after opicapone introduction. This was confirmed using binomial logistic regression(p=0.026), ordinal logistic regression without adjusting(p=0.027) and after adjusting by age, sex, PD duration and levodopa equivalent dose(LEDD)(p=0.009). Being heterozygous for rs4818 variant was associated with clinical improvement based on GCI score after the introduction of opicapone, using ordinal logistic regression adjusting by the same factors(p=0.046). No significant association was found between the other COMT and UGT1A variants and clinical responses with opicapone.

Conclusion: The rs4680 variant was associated to a reduced risk of worsening in motor fluctuations, and the rs4818 heterozygosis state to a clinical improvement according to their CGI score. These results shed light on the possible use of pharmacogenetics to help in predicting drug response in PD patients.

References: 1. Fabbri M, Ferreira JJ, Lees A, Stocchi F, Poewe W, Tolosa E, et al. Opicapone for the treatment of Parkinson’s disease: A review of a new licensed medicine: Opicapone in The treatment of PD. Mov Disord. 2018 Oct;33(10):1528–39.
2. Ferreira JJ, 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 fluctua- tions: a randomised, double-blind, controlled trial. Lancet Neurol. 2016;15(2):154–65.
3. Reichmann H, Lees A, Rocha J-F, Magalhães D, Soares-da-Silva P. Effectiveness and safety of opicapone in Parkinson’s disease patients with motor fluctuations: the OPTIPARK open-label study. Transl Neurodegener. 2020 Dec;9(1):9.
4. Bialecka M, Kurzawski M, Klodowska-Duda G, Opala G, Tan EK, Drozdzik M. The association of functional catechol-O-methyltransferase haplotypes with risk of Parkinson’s disease, levodopa treatment response, and complications. Pharmacogenetics and Genomics. 2008 Sep;18(9):815–21.
5. Politi C, Ciccacci C, Novelli G, Borgiani P. Genetics and Treatment Response in Parkinson’s Disease: An Update on Pharmacogenetic Studies. Neuromol Med. 2018 Mar;20(1):1–17.

« Back to 2023 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/effect-of-variants-in-comt-and-ugt1a-genes-on-clinical-response-in-patients-with-parkinsons-disease-treated-with-opicapone/