Utilization of COMT inhibitors, dopamine agonists, and MAO-B inhibitors with levodopa-carbidopa instestinal gel in advanced Parkinson's disease patients: Summary of phase 3 and real-world studies

Abstract

Levodopa remains the most effective treatment for Parkinson's disease (PD); however, as disease evolves, uncontrolled motor and non-motor symptoms with chronic oral therapy may necessitate the use of advanced therapies. Continuous levodopa delivery with levodopa-carbidopa intestinal gel (LCIG) improves motor fluctuations and may reduce the need for concomitant dopamine replacement therapies (DRT). This analysis summarizes add-on medication use in advanced PD patients before and after LCIG treatment from a phase 3 study and real-world observations. Add-on PD medication use including catechol-O-methyl transferase (COMT) inhibitors, dopamine agonists (DAs), and monoamine oxidase (MAO)-B inhibitors was determined at baseline (recent use before LCIG) and after approximately 1 year of LCIG treatment from a phase 3 study (NCT00335153), UK-based retrospective chart review (IRAS ID: 135453), and GLORIA observational registry. The phase 3 trial required LCIG monotherapy (no concomitant PD medications) from LCIG initiation to treatment week 4, after which adjunctive medication use was permitted. In the phase 3 study, patients using COMT inhibitors decreased from 28% to 1%, representing a 96% reduction. Under real-world conditions, patients using COMT inhibitors decreased from 23% to 2% in the retrospective chart review and from 57% to 9% in the GLORIA registry, representing 91% and 84% reductions, respectively. Decreased DA and MAO-B inhibitor use after LCIG therapy were observed in all three studies (Fig. 1). This summary of 840 advanced PD patients treated in a controlled clinical trial setting or during routine clinical care highlights reductions in add-on DRT use following 12 months of LCIG treatment.