Objective: To explore if catechol-O-methyl-transferase inhibition (COMT-I) can prolong the efficacy of daytime intrajejunal Levodopa infusion (IJLI) in Parkinson’s disease (PD) along with a reduction in vascular risk factors.

Background: From experience in our centre, COMT-I in combination with IJLI can be effective in reducing 3-O-Methyldopa (3-OMD), an inactive metabolite of Levodopa, which competes with levodopa absorption. Furthermore, it might reduce plasma homocysteine levels, a proposed, although controversial risk factor for vascular events, and nonmotor symptoms (NMS) such as cognitive dysfunction and peripheral neuropathy.

Methods: In this observational ongoing audit based European study, data from King’s College Hospital IJLI registry is reported. Thus far six PD patients, who were treated with IJLI and subsequent addition of single-dose COMT-I (Entacapone 200mg/day or Opicapone 50mg/day), were included. Tolerability, levodopa equivalent daily dose (LEDD), plasma homocysteine and liver enzyme levels (Gamma-glutamyl transferase (GGT) and alkaline phosphatase (AP)) were assessed and baseline Parkinson´s KinetiGraph (PKG) data as well as Parkinson’s disease sleep scale (PDSS) and Parkinson’s disease questionnaire 8 (PDQ-8) scores were gathered.

Results: COMT-I in combination with IJLI was well tolerated during the 4-month treatment period assessed, leading to a total LEDD reduction of 16.5% (from a mean of 1911mg/day to 1596mg/day). There was a reduction in homocysteine levels of 21.3% (from a mean of 24.5mg/dl to 19.3mg/dl) and also a 16.7% reduction of GGT levels and 4.2% of AP levels. Baseline PKG recordings indicated high bradykinesia and dyskinesia scores which had prompted IJLI therapy. Baseline PDSS and PDQ-8 scores were high at an average of 112 points for the PDSS (range 85-127) and 11 points for the PDQ-8 (range 6-19) indicating poor sleep and a reduced quality of life. Subjectively, all patients reported subjectively improved sleep after COMT-I addition.

Conclusions: COMT-I in addition to IJLI is well tolerated, may potentiate its clinical effect by a reduction in total LEDD and may reduce homocysteine levels. Of note, there was no increase in dyskinesias, despite of high dyskinesia scores at pre-infusion baseline. Adding COMT-I to IJLI also improved sleep, potentially via enhanced nocturnal control of parkinsonism.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/combined-catechol-o-methyl-transferase-inhibition-and-intrajejunal-levodopa-infusion-a-real-life-single-centre-experience/