Real‐life benefits of intrajejunal levodopa infusion therapy in four patients with the parkinsonian variant of progressive supranuclear palsy: A 1‐year follow‐up data report

Abstract

Background: Progressive supranuclear palsy (PSP) is a progressive neurodegenerative condition presenting with different clinical endophenotypes. The parkinsonian variant of PSP (PSP-P) is characterised by early but fading responsiveness to high-dose levodopa therapy; however, high-dose oral therapy is often associated with intolerance due to dopaminergic side effects and so doses may have to be capped despite clinical benefits. Evidence from animal models and real-life registries suggest far higher doses of levodopa can be tolerated if given in a continuous drug delivery (CDD) manner. We investigated tolerance and possible clinical benefits in patients with PSP-P still responsive to levodopa after initiating CDD in the form of intrajejunal levodopa infusion (IJLI) therapy as part of a compassionate usage program (CU).Methods: This is an observational clinical data report from the IJLI implementation program undertaken in regional tertiary referral Parkinson's centres in India and at King's College Hospital London, Dubai as part of a CU. Four patients with PSP-P receiving IJLI as a part of a CU underwent evaluations of liver and renal function, motor and nonmotor function, quality of life, sleep dysfunction, fatigue, anxiety and depression, and cognitive impairment at baseline and 6 and 12 months post-IJLI initiation.Results: In total, three out of four patients successfully completed 12 months of treatment (6 months in one patient). All four patients showed good tolerability to IJLI even at higher doses (1400 and 1960 mg at 6 and 12 months, respectively) when compared to oral levodopa (812.5 ± 103 levodopa equivalent daily dose [LEDD]) and presented with overall persistent improvements in motor and nonmotor scores and quality-oflife scores at 6 and 12 months post-IJLI. All patients showed improvement in estimated glomerular filtration rate (43.50 ml/min/1.73 m 2 to 67.5 ml/min/1.73 m 2 and 79.5 ml/min/1.73 m 2 at 6 and 12 months, respectively).

Can Continuous Levodopa Delivery Be Achieved in the Absence of Intrajejunal Levodopa Infusion? Implications for India and Underserved Countries

“…A discussion on latest developments in levodopa delivery and its affordability is, therefore, relevant in a global context. LCIG infusion, in particular, is one of the most effective therapies in advanced PD, with recent data suggesting efficacy shown for at least 13 years in advanced PD as well as in a small cohort of parkinsonian patients with progressive supranuclear palsy 18,19 . Next to these established treatment strategies, several new device‐aided therapies have been tested in phase 3 randomized controlled trials with positive results and wait formal licensing.…”

“…LCIG infusion, in particular, is one of the most effective therapies in advanced PD, with recent data suggesting efficacy shown for at least 13 years in advanced PD as well as in a small cohort of parkinsonian patients with progressive supranuclear palsy. 18 , 19 Next to these established treatment strategies, several new device‐aided therapies have been tested in phase 3 randomized controlled trials with positive results and wait formal licensing. These include levodopa‐entacapone‐carbidopa intestinal gel (LECIG) infusion (already approved in several countries), subcutaneous levodopa/carbidopa, 20 and subcutaneous foslevodopa/foscarbidopa preparations, 20 , 21 , 22 which are soon to enter the market with the aim to mimic CDS.…”