Levodopa Intestinal Gel Seen to Ease Long Off Periods of Advanced Disease

Levodopa/carbidopa intestinal gel (LCIG), a formulation of levodopa and carbidopa infused into the intestines, can lower the duration of off episodes in people with advanced Parkinson’s disease, and is likely to be especially helpful to those whose daily episodes are long-lasting, an analysis of registry study data show.

A majority of patients in these analyses were experiencing off periods of at least three hours a day before starting treatment, the researchers wrote.

The study, “Predictors of Response for “Off” Time Improvement With Levodopa-Carbidopa Intestinal Gel Treatment: An Analysis of the GLORIA Registry,” was published in the journal Frontiers in Neurology.

Levodopa-based treatments increase the levels of dopamine, a brain chemical essential for balance and movement coordination whose levels are very low in people with Parkinson’s. They are currently the main forms of treating this disease’s motor symptoms.

However, side effects that include off episodes — periods where symptoms return before another dose can be taken — are common in patients on these treatments for years.

LCIG, developed by AbbVie (brand name, Duodopa) and available in countries including the U.S. and EU, is a long-term therapy for patients at advanced stages of Parkinson’s. It allows for levodopa and carbidopa to be continuously infused into the upper intestine, via a soft plastic tube surgically inserted through the skin and with the help of a portable pump.

Previous studies suggest that LCIG is effective at reducing symptom fluctuations associated with the long-term use of levodopa-based therapies in patients with advanced Parkinson’s.

However, “one critical data gap is determining when to transition a patient to a more advanced therapy and baseline characteristics that would predict a favorable response to LCIG therapy,” that researchers wrote.

In this study, scientists at AbbVie in collaboration with colleagues at the University of Innsbruck and at the University of Padua analyzed data from a registry study to identify factors that could predict which patients would benefit most after starting LCIG.

The global registry study, called GLORIA (Global LOng-term Registry on efficacy and safety of LCIG in patients with Advanced Parkinson’s disease in routine care), documented the clinical outcomes of advanced Parkinson’s patients using LCIG in a routine care setting for two years.

Of the 375 patients enrolled in the registry, 152 had data available on the treatment’s effectiveness at both the study’s start (baseline data) and its end. This smaller group was included in post-hoc analyses.

Nearly all, 86% or 131 patients, saw off episodes lessen by at least one hour after two years of treatment, the minimum amount of time a treatment could be considered as giving a clinically meaningful benefit. More than half — 64% or 97 patients —  experienced reductions in off time of three or more hours.

Patient characteristics at baseline were similar in those experiencing a lesser reduction in off time (called weak responders) and those with a greater, three or more hour, reduction after two years of treatment (called robust responders).

But robust responders also had shorter episodes of dyskinesia (involuntary movements) before starting with LCIG.

Despite a more modest, median of 33% reduction in the duration of off time, weak responders saw their time with dyskinesia decline by a median of 44%. This was similar to that seen for dyskinesia in robust responders, with a median reduction of 50% from baseline after two years of treatment.

The duration of off episodes that patients experienced before treatment with LCIG was the best and only factor that could significantly predict who was more likely to have the greatest reduction in off time with treatment, the study noted.

“Overall, these data provide important real-world clinical evidence to confirm the efficacy of LCIG therapy for ‘Off’ time reduction. These results are encouraging and show that patients with severe motor fluctuations in terms of amount of daily ‘Off’ time are likely to show the most impressive response to LCIG therapy,” the researchers wrote.

“These data provide important clinical information related to LCIG patient selection and therapeutic response when considering advanced therapies,” they added.