Experience from Clinical Practice with Intestinal Gel LECIG in Treating Parkinson's Disease

LCIG and LECIG in the Treatment of Parkinson's Disease

Continuous infusion of levodopa/carbidopa in an intestinal gel (LCIG) is a well-established approach in treating Parkinson's disease with motor fluctuations. It ensures stable levodopa plasma concentrations and its delivery to the brain. It effectively reduces motor fluctuations and dyskinesias, as well as some non-motor fluctuations. It improves patients' quality of life and can be used for many years. However, many patients complain about the size and weight of the portable pump required for the application, and the treatment is also associated with the risk of developing peripheral neuropathy.

In order to reduce the required dose of levodopa, along with carbidopa, which reduces the peripheral metabolism of levodopa to dopamine, catechol-O-methyltransferase (COMT) inhibitors are also administered to block another pathway of its peripheral metabolism. When COMT inhibitors entacapone or tolcapone are given orally together with LCIG, the levodopa dose can be reduced by 20% while maintaining its stable concentration and efficacy. Therefore, an intestinal gel containing levodopa/entacapone/carbidopa (LECIG) was developed. Entacapone was chosen due to its better safety profile. The gel is applied via a portable pump directly into the duodenum or upper jejunum using a permanent tube. This tube is inserted percutaneously through a gastrostomy with an external transabdominal tube and an internal intestinal tube. An alternative solution is radiological gastrojejunostomy. The pump with an inserted cassette can be worn on the body for up to 16 hours; during treatment at night, it can be placed, for example, on a bedside table.

Based on a comparison of LCIG and LECIG in a randomized crossover study, LECIG was approved for clinical use in Sweden in 2018. In the Czech Republic, LECIG has been registered since 2021.

Findings from the Swedish Observational Study with LECIG

Swedish authors recently published their experiences with using LECIG in clinical practice. Monitoring took place from June 2019 to January 2021. The main evaluated parameters were efficacy, tolerability, and usability from the patients' perspective during the first year of use. A total of 24 patients (11 women and 13 men) with idiopathic Parkinson's disease, with an average age of 71.5 years, were evaluated. The median disease duration was 15.5 years. The median duration of LECIG use was 305 days, the median morning dose was 6.0 ml, additional doses were 1.0 ml, and the infusion rate was 2.5 ml/hour.

The median daily dose of levodopa decreased from 1210 mg (range 435–2400 mg) before using LECIG to 1040 mg (370–2000 mg) at the start of LECIG use and 1080 mg (510–1822 mg) at the end of the evaluation. Six patients stopped LECIG treatment, three of them due to diarrhea, one due to hallucinations, and two died (one from COVID-19 and one from cardiac arrest). Three other patients had adverse events that did not lead to discontinuation of treatment - these included sweating, nausea, and chills.

Half of the patients were switched to LECIG directly from LCIG, and another three had previously used LCIG. These patients particularly appreciated the smaller size and weight of the pump, and most described the new pump as more user-friendly. Of the patients who had not previously used levodopa in infusion form, 70% reported symptom alleviation with LECIG. Patients switched from LCIG to LECIG mostly indicated no change or slight improvement. Most patients reported in the questionnaire an improved ability to perform daily activities and an improved quality of life according to their self-assessment. Most patients managed the pump well, but 13 reported not always having enough time to press the appropriate button before the device switched back to the menu, and two considered this a major issue.

Conclusion

This observational study showed that LECIG is a viable therapeutic option in clinical practice for patients with Parkinson's disease, demonstrating expected efficacy and safety. Patients were generally satisfied with the size and operation of the pump. According to the study authors, some technical improvement of the pump is needed, and larger prospective studies should be conducted.  

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Sources:
1. Öthman M., Widman E., Nygren I., Nyholm D. Initial experience of the levodopa-entacapone-carbidopa intestinal gel in clinical practice. J Pers Med 2021 Mar 31; 11 (4): 254, doi: 10.3390/jpm11040254.
2. SPC Lecigimon. Available at: www.sukl.cz/modules/medication/download.php?file=SPC174367.pdf&type=spc&as=lecigimon-spc