#AANAM – CLES Led to Sustained Reductions in ‘Off’ Time

Editor’s note: The Parkinson’s News Today team is providing in-depth coverage of the 2021 Virtual AAN Annual Meeting, April 17–22. Go here to read the latest stories from the conference.

Carbidopa/levodopa enteral suspension (CLES) provided long-term, sustained, and clinically meaningful reductions in “off” time for people with Parkinson’s disease, according to data from a real-world study in the U.S.

The two-year data also showed that controlling motor symptom fluctuations was associated with meaningful improvements in patients’ quality of life, which were observed early on in the study, and were maintained throughout the two years.

These findings were presented in the poster “Sustained Clinically Meaningful Improvement in Quality of Life at 24 months After Initiation of Carbidopa/Levodopa Enteral Suspension (CLES) in Advanced Parkinson’s Disease (APD) Patients in USA: Interim Results from the PROviDE Study” at the 2021 American Academy of Neurology virtual meeting, running through April 22.

CLES (duodopa), also known as levodopa/carbidopa intestinal gel (LCIG) outside the U.S., is an intestinal gel formulation of the carbidopa-levodopa combo developed by AbbVie.

The therapy has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of motor fluctuations in patients with advanced Parkinson’s disease.

Administered via a small, portable infusion pump it delivers the medication directly into the small intestine continuously for 16 hours daily.

Data from clinical studies have shown that CLES significantly reduced the time when standard levodopa treatment wears off — periods known as “off” times — and improved patients’ quality of life.

However, most data is derived from studies in Europe, and real-world evidence of the therapy’s effectiveness in the U.S. is lacking.

The Pursuing real-world Outcomes via Duodopa Ecosystem (PROviDE) observational study was designed to evaluate the real-world, long-term effectiveness of CLES in patients with advanced Parkinson’s living in the U.S.

The prospective study, underway for three years, followed patients from their homes and constituted the “largest U.S-specific cohorts of patients with APD [advanced Parkinson’s disease]” being treated with CLES for a long period of time, the researchers wrote.

Its primary goal was to assess changes in patient’s reported “off-time” per day.

Additional (secondary) goals included measures of quality of life — assessed using the Parkinson’s Disease Questionnaire 8 (PDQ-8) — and treatment satisfaction, as measured using the Treatment Satisfaction Questionnaire for Medication version 9, TSQM-9.

PDQ-8 is a measure of health-related quality of life, in which higher scores indicate poorer quality. TSQM-9 assesses patients’ satisfaction with medication, using a range of zero to 100 with higher scores indicating increased satisfaction.

In total, the analysis included 38 patients (mean age 66.6 years, 65.8% men). At the start of the trial, the mean “off” time (normalized to a 16-hour waking day) was 6.2 hours, the mean PDQ-8 score was 43.4, and the mean TSQM-9 score was 44.9.

Treatment effect was assessed at 3, 6, 12, 18, and 24 months after the study began

Following CLES treatment for up to 24 months, “off” times were reduced significantly at all time intervals measured by three hours or more (mean 6.2 vs 2.7 hours/day). A reduction of one hour in “off” time is considered clinically meaningful.

This reduction was sustained for more than two years following the start of CLES treatment.

Quality of life was significantly improved after treatment started, as shown by marked reductions in the PDQ-8 score observed in all measured times points, which were sustained until the end of the 24 months.

The biggest improvement was observed at 18 months post-treatment, with a drop of 9.7 points in the PDQ-8 score. (A drop of 5.7 points in the PDQ-8 score is considered clinically meaningful).

Treatment satisfaction also was significantly improved, especially regarding satisfaction with the effectiveness of treatment, as well as convenience.

Overall, the results show that CLES treatment “provides sustained clinically meaningful reduction in ‘OFF’-time in the real-world U.S. setting that is similar to improvements reported in clinical trials,” the researchers concluded.