Levodopa–carbidopa intestinal gel for treatment of advanced Parkinson’s disease

Abstract

Background:

Levodopa is the mainstay of Parkinson’s disease (PD) treatment, but is often eventually associated with disabling motor complications in patients with advanced PD. The inability of perorally administered levodopa to provide more physiologic continuous dopaminergic stimulation (CDS) is a leading hypothesis to explain these complications.

Objective:

To investigate the cumulative efficacy and safety, and re-evaluate the role, of levodopa–carbidopa intestinal gel (LCIG) infusion in treatment of advanced PD patients experiencing levodopa-associated motor complications, through its purported mechanism for providing CDS.

Methods:

Literature searches in the MEDLINE/PubMed database were used to identify peer-reviewed publications examining the role of CDS in levodopa-associated motor complications and pharmacologic strategies for CDS, focusing on LCIG infusion for advanced PD patients.

Results:

LCIG, an aqueous gel, is continuously infused (daytime only or 24 h) via a portable pump and tube permanently inserted into the duodenum through percutaneous endoscopic gastrostomy (PEG). LCIG infusion provides stable levodopa plasma levels, which are significantly less variable than those with oral levodopa. Clinical trials indicate LCIG may significantly improve motor complications (reduction of time in ‘off’ and time in ‘on with dyskinesias’), motor scores using the Unified Parkinson’s Disease Rating Scale (UPDRS), non-motor symptomatology (Non-motor Symptom Scale) and health-related quality of life (HRQOL) in advanced PD patients. The adverse-event profile of LCIG is similar to that of oral levodopa, although technical problems with the infusion device have occurred in up to 70% of patients.

Conclusion:

LCIG has demonstrated efficacy in reducing levodopa-associated motor complications in patients with advanced PD, and improving UPDRS and HRQOL scores. Because it involves PEG and its associated risks, LCIG is recommended for patients in whom motor fluctuations and dyskinesias are inadequately treated with traditional peroral medication. For these patients, LCIG can be a valuable alternative to deep brain stimulation (DBS), especially when DBS is contraindicated. These conclusions are limited by the modest number and size of completed randomized, controlled trials of LCIG.

Key words::

• continuous dopaminergic stimulation
• dyskinesias
• levodopa-carbidopa intestinal gel
• motor fluctuations
• Parkinson’s disease

Transparency

Declaration of funding

This article was supported by Abbott Laboratories.

Declaration of financial/other relationships

H.H.F. participated as a site-PI for LCIG studies, and is a member of the Steering Committee/a Team Leader for the United States, for the current double-blind and open-label LCIG global studies. However, a contract has been made for these services between Solvay/Abbott and the University of Florida/Cleveland Clinic Foundation and no compensation has been received personally by Dr Fernandez. P.O. has participated as site-PI for several LCIG studies. However, a contract has been made for these services between Solvay/Abbott and Central Hospital Bremerhaven and no compensation has been received personally by Dr Odin.

CMRO peer reviewers may have received honoraria for their review work. The peer reviewers on this manuscript have disclosed that they have no relevant financial relationships.

Acknowledgements

The authors would like to thank the Curry Rockefeller Group for providing editorial support. Funding for this support was provided by Abbott. The authors accept sole responsibility for the content and accuracy of the manuscript and also had final responsibility for the decision to submit for publication.

Notes

*Duodopa is a registered trade name of Abbott Products GmbH, Hannover, Germany.