Objective: To elucidate which levodopa-treated COMT-naïve Parkinson’s Disease (PD) patients were at higher risk for developing dyskinesia when starting opicapone (OPC) 50mg or entacapone (ENT).

Background: OPC, a new once-daily COMT inhibitor, has shown to be effective in the treatment of motor fluctuations in PD patients in two large, pivotal, multinational trials (BIPARK-I and II) [1,2].

Methods: Double-blind, 14 to 15-week, placebo- and active-controlled study. In the emergence of dopaminergic adverse-events (AE) during the first 3-weeks of treatment, investigators could titrate the levodopa daily-dose. Dopamine-agonists (DA) and MAO-B inhibitors (MAO-Bi) for the treatment of PD were allowed provided the regimen remained stable 4-weeks before and throughout the study. Dyskinesia-related AEs were defined as new or worsening of baseline dyskinesia. This subgroup analysis investigated the association of dyskinesia according to the daily-dose of levodopa (<700mg; ≥700mg) as well as concurrent use of DA/MAO-Bi.

Results: A total of 359 patients were randomized to placebo (PLC, n=121), OPC-50mg (n=116) or ENT (n=122). Patients taking OPC-50mg presented more frequently with dyskinesia (16%) compared to ENT (8%) and PLC (4%). Patients with concurrent use of DA and taking levodopa ≥700mg at baseline appeared to be at higher risk of developing dyskinesia. About 64% of all patients with dyskinesia-related AEs had a levodopa daily-dose reduction of ~25%. No new dyskinesia-related AEs were reported during maintenance period for patients on OPC-50mg who reduced their levodopa daily-dose during adjustment period.

Conclusions: High levodopa daily-dose and concomitant DA use were associated with a higher risk of developing treatment-emerging dyskinesia. Patients who develop dyskinesia after starting OPC may benefit from a reduction of their daily-dose of levodopa. Early follow-up within the first weeks of treatment may be warranted, particularly in patients taking high levodopa daily-dose (≥700mg) concomitantly with DA.

References: 1. Ferreira JJ, Lees A, Rocha JF, Poewe W, Rascol O, Soares-da-Silva P, et al. Opicapone as an adjunct to levodopa in patients with Parkinson’s disease and end-of-dose motor fluctuations: a randomised, double-blind, controlled trial. Lancet Neurol 2016;15:154-165. 2. Lees AJ, Ferreira J, Rascol O, Poewe W, Rocha JF, McCrory M, et al. Opicapone as Adjunct to Levodopa Therapy in Patients With Parkinson Disease and Motor Fluctuations: A Randomized Clinical Trial. JAMA Neurol 2017;74:197-206.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/dyskinesia-management-in-comt-naive-patients-starting-adjunctive-therapy-with-opicapone-the-bipark-i-double-blind-experience/