Treatment Options for Advanced Parkinson's Disease Using Medical Devices (DAT)
A new treatment option for advanced Parkinson's disease (PD) using medical devices (DAT − device-aided therapy) is the intestinal infusion gel containing levodopa, entacapone, and carbidopa (LECIG). An article published in 2022 in the journal Therapeutic Advances in Neurological Disorders provides an overview of current DAT modalities in PD patients and presents LECIG as the latest extension of options in this area.
Treatment of PD Using DAT
As Parkinson's disease progresses, oral and transdermal medication regimens may no longer sufficiently control OFF states, and motor complications may arise. For these patients, it is necessary to consider DAT, which offers continuous dopaminergic stimulation. Currently, deep brain stimulation (DBS), continuous subcutaneous apomorphine infusion, or levodopa infusion directly into the upper jejunum can be used. These methods have never been directly compared, but individual studies show very similar efficacy. They are relatively well tolerated, though with varying profiles of adverse events. Not every DAT option is suitable for every patient. An individualized approach is necessary, selecting the most appropriate option based on the clinical picture, personal situation, and patient preferences. Patients need to be properly informed about all available DAT options so they can express their informed preferences during consultations with a neurologist.
Deep Brain Stimulation (DBS)
DBS requires the surgical insertion of an electrode into the subthalamic nucleus, globus pallidus medialis, or nucleus ventralis intermedius in the brain. High-frequency stimulation of these nuclei has demonstrated long-term improvement in motor fluctuations and dyskinesia in patients with advanced PD.
Subcutaneous Apomorphine Infusion
The least invasive DAT is continuous subcutaneous apomorphine infusion. Currently, it is the only non-surgical DAT method. Several short-term and long-term studies have shown its efficacy in reducing OFF states by up to 80% and alleviating dyskinesia while simultaneously reducing oral levodopa doses.
Intestinal Gel LCIG
Intestinal infusion of the gel containing levodopa and carbidopa (LCIG) is administered directly to the proximal jejunum after surgically creating a percutaneous endoscopic gastrostomy, using a jejunal extension tube (PEG-J) with a portable programmable infusion pump. The efficacy and safety of LCIG have been demonstrated in several prospective studies. A 12-week double-blind comparison with standard levodopa administration, a 52-week open-label extension, and a 54-week follow-up for safety showed significant improvement in the ratio of OFF and ON states without dyskinesia and long-term quality of life preservation. A systematic review of long-term published data on LCIG treatment confirmed a persistent effect on reducing OFF states.
LECIG Infusion
Intestinal infusion of LECIG represents the newest available DAT. The method of administration is very similar to LCIG using the PEG-J system, but with the addition of a smaller specially designed lightweight pump. In patients treated with LCIG, the catechol-O-methyltransferase (COMT) inhibitor entacapone is sometimes co-administered, which increases the bioavailability of levodopa. LECIG contains entacapone directly in the infusion, allowing a reduction in the total daily dose of levodopa while achieving its equally effective and stable plasma concentration. Additionally, it bypasses the need for multiple daily doses of oral entacapone. Patients suitable for DAT can be transitioned to LECIG from oral medication or another DAT using a simple step-wise dose calculation and titration. For LCIG patients, the PEG-J system is compatible with LECIG, facilitating treatment transition. This is a relatively new product, and its long-term safety and efficacy still need to be verified. Real-world data will contribute to this verification.
Conclusion
LECIG infusions represent the latest extension of DAT options for treating advanced Parkinson's disease. Today, this method can be considered as useful as DBS, subcutaneous apomorphine infusion, or intestinal LCIG infusion. Clinical studies and existing practice experiences show similar efficacy of LECIG infusions to LCIG, but with a reduction in the total dose of levodopa due to increased bioavailability enabled by the addition of entacapone to the infusion. The smaller dose of levodopa offers the advantage of lower exposure to its potentially harmful metabolites.
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Source: Nyholm D., Jost W. H. Levodopa-entacapone-carbidopa intestinal gel infusion in advanced Parkinson's disease: real-world experience and practical guidance. Ther Adv Neurol Disord 2022 Jun 26; 15: 17562864221108018, doi: 10.1177/17562864221108018.
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