Levodopa-Carbidopa Gel Safely Reduces Parkinson's Disease Tremors
VANCOUVER, BC—Patients with advanced Parkinson's disease had resting tremors improved with levodopa-carbidopa intestinal gel, a study presented at the 68th Annual AAN Meeting has found.
"Levodopa-carbidopa intestinal gel may alleviate resting tremor that was not well controlled by optimized oral medication in patients with advanced Parkinson's disease," noted lead study author Hubert Fernandez, MD, of the Center for Neurological Restoration, Cleveland Clinic, Cleveland, OH.
In patients with advanced Parkinson's disease, 70% to 100% report resting tremor. Although typically treated with dopaminergic or agents such as amantadine, "the resting tremor response to dopaminergic therapy is often regarded as insufficient and underpins one of the reasons why deep brain stimulation, which requires an invasive procedure, may be chosen over other non-oral therapies in advanced Parkinson's disease," he stated.
Dr. Fernandez and colleagues evaluated the effect of levodopa-carbidopa intestinal gel administered via a percutaneous endoscopic gastrojejunostomy (PEG-J) tube in a Phase 3, 12-month open-label study. Following a screening period, during which patients were converted to and stabilized on oral levodopa monotherapy, a PEG-J tube was surgically placed.
"The Unified Parkinson's Disease Rating Scale (UPDRS) Part III Question 20 (resting tremor) total score (5 categories: arms, legs, and face) was used to stratify patients into 3 subgroups defined by their maximum baseline tremor score," he noted. "Efficacy and safety were evaluated in the context of these 3 baseline tremor subgroups."
Patients recorded "on" and "off" time with troublesome dyskinesia using the Parkinson's Disease Symptom Diary.
Of the 354 patients enrolled in the study, 196 (69%) had no baseline tremor, 38 (13%) had mild baseline tremor, and 52 (18%) had significant baseline tremor.
Results showed that across all 3 subgroups, mean change from baseline to final levodopa dose was similar, and amantadine use decreased from approximately 30% at baseline to approximately 10% during the study.
"The mean change from baseline in UPDRS Part III Question 20 total scores was greater in patients with significant baseline tremor than in patients with mild baseline tremor," Dr. Hernandez reported.
Overall, use of the levodopa-carbidopa intestinal gel resulted in 78% of patients in the mild tremor group experiencing a 100% reduction in resting tremor; among those with significant tremor, 70% experienced a 100% reduction. "Two patients (5%) in the mild tremor group and 3 (6%) in the significant tremor group experienced a worsening of resting tremor," he noted. "Improvements in reducing 'off' time and increasing 'on' time without troublesome dyskinesia were comparable across subgroups."
Adverse events were observed in 94% of patients, and serious adverse events in 32%, with rates being similar across the 3 baseline tremor subgroups. Serious adverse events that occurred in >3% of patients included complication of the PEG-J device insertion, polyneuropathy, and pneumoperitoneum.
"Controlled, prospective studies are need to confirm the improvement in tremor seen with levodopa-carbidopa intestinal gel treatment in this study," Dr. Fernandez concluded.