COMT inhibition in PD: are we making the most of it?

Fabrizio Stocchi & Joaquim Ferreira

The third and final debate of the PD Summit focused on the question, COMT inhibition in PD: are we making the most of it? A vote taken before the debate showed that three-quarters of the audience thought that more could be made of COMT inhibition in PD, so Fabrizio Stocchi had a difficult case to make in favour.

He outlined how, as hard as we try to provide continuous dopamine stimulation with PD therapies, oral levodopa only provides pulsatile stimulation of striatal dopamine receptors. A number of attempts have been made to provide more continuous delivery of dopamine, including intrajejunal levodopa administration and more frequent administration of oral levodopa with entacapone (including the 2010 STRIDE-PD trial, led by Stocchi²), but without significant success. He went on to conclude that providing continuous dopamine stimulation remains an unmet need in the approach to Parkinson’s treatment.

Joaquim Ferreira had the easier task of arguing that more could be made of COMT inhibition in PD, in line with the audience majority. He noted that not all COMT inhibitors are alike, and drew on findings from the opicapone pharmacokinetics 203 trial³ and the ADOPTION clinical programme¹ to support the role of opicapone as an early add-on to levodopa in patients with PD and OFF symptoms. He argued that whilst the primary endpoint of the STRIDE-PD trial was negative, there were positive secondary outcomes and much had been learned from this pioneering trial.² He argued for a role for COMT inhibition much earlier in the development of motor fluctuations as a way to optimise levodopa.

A vote taken after the debate showed that even more of the audience (83%) were persuaded that more can be made of COMT inhibition in PD.