Levodopa–Entacapone–Carbidopa Intestinal Gel in advanced Parkinson’s disease: clinical positioning, candidate profiling, and implementation roadmap

Device-aided therapies (DATs) for Parkinson’s disease (PD) with motor complications encompass deep brain stimulation (DBS), intrajejunal and subcutaneous infusions. Levodopa-carbidopa-entacapone intestinal gel (LECIG) infusion is the most recent strategy to be included in the intrajejunal class. By adding peripheral catechol-O-methyltransferase (COMT) inhibition, LECIG increases levodopa bioavailability, enabling a comparable dopaminergic effect at a reduced levodopa dose and infusion volume. Drawing on the discussion of a national advisory board of Italian movement disorder specialists, this perspective addresses the positioning of LECIG in PD patients with motor fluctuations. LECIG broadens the intrajejunal infusion landscape with a smaller device and potential metabolic advantages related to reduced 3-O-methyldopa generation. Two candidate scenarios predominate: the patient requiring a first infusional DAT after failure of optimized oral therapy who is ineligible for or declines DBS, and the patient already on a DAT with residual or worsening/re-emergent fluctuations. Favorable selection features include a levodopa-responsive, motor-fluctuation-predominant phenotype, documented COMT-inhibitor tolerance, absence of overt dementia with adequate caregiver support, a rationale for levodopa dose sparing (e.g., peripheral neuropathy risk), and concomitant dysphagia that features an additional niche benefitting of intestinal therapies. Cautionary or unfavorable features include levodopa-resistant axial disability, severe cognitive impairment, absence of caregiver support, COMT-inhibitor intolerance, and active neuropsychiatric symptoms, other than gastrointestinal contraindication for receiving gastrojejunostomy. Implementation barriers include the need for structured gastroenterology collaboration, and a potential cost-per-quality-adjusted-life-year higher than comparator DATs. Precise, multidimensional patient selection, together with a prescribing roadmap, with prospective registries, and structured multidisciplinary agenda, could be the cornerstone of optimizing outcomes.