Objective: To study the effect of COMT inhibitors (opicapone and entacapone) in Parkinson’s disease (PD) patients on levodopa-carbidopa intestinal gel (LCIG) and an insufficient control of motor symptoms.

Background: LCIG is an effective treatment for patients with advanced PD. Addition of a COMT inhibitor, that blocks levodopa’s second-largest pathway, leads to less levodopa conversion to 3-O-methyldopa (3-OMD), increasing the concentration of levodopa in plasma. In addition, as 3-OMT competes with levodopa to pass the blood brain barrier, COMTis allow more levodopa to enter the brain. Finally, the inhibition of COMT reduces the concentration of some levodopa metabolites that could have a neurotoxic effect and the requirements of vitamins B12, B6 and folic acid.

Method: Retrospective analysis of patients undergoing treatment with LCIG who presented an insufficient motor control despite several infusion adjustments.  Opicapone was added when there were predictable fluctuations several times a day or unpredictable fluctuations, while entacapone was added for predictable fluctuations, usually postprandial. Both drugs were prescribed once a day. The dose of levodopa was reduced about a 10% only with opicapone. Fluctuations were measured with Hauser’s diaries. Homocysteine ​​levels were studied before and after treatment. All patients were on vitamin B12 and folic acid supplements.

Results: Sixteen patients mean age 72,2 + 6.5 years, evolution of PD 9,5 + 7,3 years (11 opicapone, 5 entacapone; 8 and 2 with LCIG 24 hours respectively). Daily mean dose of LCIG was 1321,4 mg in the opicapone group and 1028,7 mg in entacapone one. All patients had motor fluctuations and 6/11 also had unpredictable fluctuations. Opicapone reduced OFF time by 1.2 + 0.9 hours (range 0,0-3,1, p = 0,2), and entacapone by 0,2 + 0,2 (range 0,0-0,5). The mean dose reduction of levodopa was 16 + 21 mg/hour, 235,2 mg/day, a 17.8% reduction; the number of extra doses used was reduced from 4,6 to 2,1. A cost analysis yielded a reduction in the cost of LCIG of 3540 euros per patient and year, once opicapone costs were discounted. There were no differences between basal and follow-up homocysteine ​​levels.

Conclusion: Opicapone and entacapone may be useful for controlling motor fluctuations of patients with PD undergoing treatment with LCIG when therapeutic adjustment is insufficient.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/opicapone-and-entacapone-as-add-on-therapy-to-the-treatment-of-infusions-of-levodopa-carbidopa-intestinal-gel-in-patients-with-advanced-parkinsons-disease/