German Delphi consensus: COMT inhibitors in the management of wearing-off fluctuations in Parkinson’s disease

COMT inhibitors (COMT-Is) have now been established for thirty years as adjunctive medication in the treatment of Parkinson's disease (PD). When they were first introduced, the prolonged duration of action of levodopa and the increase in levodopa levels were regarded as significant advances. Many questions regarding their practical application have not been fully addressed scientifically. This has led to a degree of uncertainty regarding the assessment of the efficacy and, consequently, the use of COMT-Is. For this reason, the aim of this Delphi consensus was to assess the current status of COMT inhibition in PD in Germany, to identify any shortcomings, and to find new approaches to close our knowledge gaps and reach a consensus on recommendations. In doing so, the authors who formulated the questions for the Delphi consensus aim to provide their colleagues with practical guidance on the use of COMT-Is in the treatment of Parkinson's symptoms. To achieve this aim, 200 specialists in movement disorders across Germany were asked to evaluate 22 statements across three subject areas. 115 specialists responded. Key findings: In topic area 1, 'Response fluctuations and the use of COMT-Is', it emerged that the Wearing-off Questionnaire, 9-item version (WOQ-9) was not unanimously regarded as a suitable tool for diagnosing response fluctuations (agreement rate: 64%). In topic area 2 (role of COMT-Is in the treatment of fluctuations in efficacy), there was a contradiction in that while COMT-Is were not considered the first-line treatment of choice (agreement rate 58%), respondents agreed that they should be used at an early stage when fluctuations in efficacy occur (agreement rate 95%). In topic area 3 (comparison of various aspects of individual COMT-Is), opicapone was unanimously rated as the easiest to manage in daily use due to its once-daily dosing and favourable safety profile (agreement rate: 83%). In summary, the survey provides significant insights into fluctuations diagnosis and the current role of COMT-I in the treatment of PD. The efficacy and tolerability/safety of opicapone observed in clinical trials for the treatment of Parkinson's patients with motor fluctuations are also confirmed in this survey in clinical practice.