Levodopa-Carbidopa Intestinal Gel Superior to Immediate Release Capsules for ON Time Without Dyskinesia

September 15, 2020

Benefits of levodopa-carbidopa intestinal gel lasted throughout the day and showed greater benefits of continuous dopaminergic stimulation in disease control than immediate release oral capsules.

Results from a post-hoc analysis of a double-dummy, double-blind, randomized, controlled trial showed that patients with Parkinson disease (PD) who were treated with levodopa-carbidopa intestinal gel (LCIG) experience a faster time to ON without troublesome dyskinesia (ON-woTD) compared with immediate-release levodopa-carbidopa oral capsules (LCIR).

The data were presented at the 2020 MDS Virtual Congress, September 12–16, 2020, by Rajesh Pahwa, MD, the Laverne and Joyce Rider Professor of Neurology; chief of the Parkinson’s and Movement Disorder Division; and director of the Parkinson's Foundation Center for Excellence at the University of Kansas Medical Center.

Pahwa and colleagues recorded patients’ motor state changes at 30-minute intervals over 3 days at baseline and 12 weeks post-treatment. At baseline, within 30 minutes of waking up, 11.3% of patients on LCIG had ON-woTD compared to 20.0% of those on LCIR, suggesting that LCIG may provide predictability to perform their daily activities without difficulty.

It was noted that prior analyses have established LCIG’s greater efficacy in reducing total patient OFF time relative to LCIR but did not fully demonstrate hour-by-hour benefits. In total, 65.5% of LGIC patients had ON-woTD 1.5 hours after turning the pump on compared to 61.7% of LCIR patients after 2.5 hours.

At the conclusion of treatment at 12 weeks, thrice (32.8%; P <.05) as many LCIG patients versus similar (26.7%; P = .39) LCIR patients had ON-woTD within 30 minutes of wake-up as compared to baseline.

Investigators assessed ON time without dyskinesia (ON-woD), commonly referred to as the best state for patients with PD, for the 16-hour working day using Wilxocon signed-rank tests and ANCOVA models. They found that LCIG also showed the ability to reduce OFF and increase ON-woD consistently throughout the day, demonstrating the benefits of continuous dopaminergic stimulation in greater disease control than LCIR.

Figuring out optimal ways to help patients with PD cope with their OFF time has always been among the top clinical concerns. Additional data presented at the 2020 MDS Virtual Congress from the phase 3b DYSCOVER study showed that treatment with LCIG significantly improved dyskinesia compared to optimized medical treatment (OMT), supporting the idea that LCIG can be an effective treatment for dyskinesia in patients with advanced PD.2

In that study, the primary end point of mean change from baseline in dyskinesia, as measured by the Unified Dyskinesia Rating Scale (UDysRS), was significantly improved in the LCIG group (n = 24; –17.4 [±2.8]) compared to the OMT group (n = 26; –2.3 [±2.6]) at week 12 (mean difference, –15.1; 95% CI, –21.5 to –8.6; <.001).

Pahwa recently sat down with NeurologyLive on Episode 16 of the “Mind Moments” podcast to discuss the challenges of medication adherence in PD and how it impacts OFF episode management. Listen in below.

For more coverage of MDS, click here.

REFERENCES
1. Pahwa R, Aldred J, Gupta N, et al. Rapid on-time onset and sustained improvements in motor states throughout the day following treatment with levodopa/carbidopa intestinal gel (LCIG) vs immediate-release levodopa/carbidopa oral capsules (LCIR). Presented at MDS Virtual Congress; September 12–16, 2020. Abstract 930.
2. Alvarez EF, Spanaki C, Pekkonen E, et al. Effect of levodopa-carbidopa intestinal gel versus optimized medical treatment on dyskinesia in advanced Parkinson’s disease patients: final results of the randomized 12-week DYSCOVER study. Presented at MDS Virtual Congress; September 12–16, 2020. Abstract 867