Single‐Center Study of 103 Consecutive Parkinson's Disease Patients with Levodopa‐Carbidopa Intestinal Gel

Abstract

Background Levodopa‐carbidopa intestinal gel (LCIG) effectively reduces off time and dyskinesia and increases on time in advanced Parkinson's disease (PD). However, patients with LCIG‐infusion experience frequent complications and some discontinue treatment early on. Objectives The objectives of this study were to find predictive factors for early dropout from the LCIG infusion, analyze the treatment burden on the tertiary health care system, and explore changes in medication during the LCIG treatment. Methods LCIG‐infusion was administrated to 103 patients between July 2006 and May 2020 at the Helsinki University Hospital, accumulating 350 years of follow‐up data. We evaluated, retrospectively, changes in medication during treatment, discontinuation of the infusion, and adverse events from the patient records. Results Living alone was a predictive factor for early dropout (OR = 3.88; 95% CI = 1.03–14.66; P = 0.045). The treatment burden on the tertiary health care system increased after the initiation of LCIG infusion mostly because of common complications related to the infusion system (median change of in‐ and out‐patient visits +1, P = 0.03). Mean levodopa equivalent daily dose (LEDD) rose from baseline to 6 months (1246.7 vs. 1684.9, P = 0.001) and stabilized thereafter. Patients commonly switched from “polypharmacy” to “LCIG‐only” or “LCIG + oral levodopa” medication‐groups during long‐term treatment. Conclusions Recurrent complications related to the infusion system increase the treatment burden on tertiary healthcare system after the initiation of LCIG‐infusion. Most patients continue long‐term with the infusion. Few patients discontinue infusion during the first year after initiation and living alone appears to be a risk factor for this outcome.

Continuous Dopaminergic Stimulation Improves Cortical Maladaptive Changes in Advanced Parkinson's Disease

“…However, this principle is not sustainable with cDS. In our study, as well as in other studies with cDS, 59 patients with PD were on higher LEDD when tested on cDS compared with iDS, because improvement of dyskinesias allowed for an increase in the total levodopa dose to reduce motor fluctuations and achieve better on motor state, resulting in the reversal of correlation between LEDD and dyskinesias subscores 59 …”

“…In our study, as well as in other studies with cDS, 59 patients with PD were on higher LEDD when tested on cDS compared with iDS, because improvement of dyskinesias allowed for an increase in the total levodopa dose to reduce motor fluctuations and achieve better on motor state, resulting in the reversal of correlation between LEDD and dyskinesias subscores. 59 Another related question is whether the changes in TMS measures reflect a higher dosage of levodopa or the change in the modality of levodopa delivery (cDS vs. iDS). We argue for the latter explanation, because the mode of dopaminergic stimulation rather than levodopa absolute dose determines the continuity of dopaminergic stimulation at the synaptic level.…”

Long-term safety, discontinuation and mortality in an Italian cohort with advanced Parkinson’s disease on levodopa/carbidopa intestinal gel infusion

“…We found an overall discontinuation of 24.1%, which is slightly lower than that found by Viljaharju et al (27.2%). The number of severe adverse events registered in the long term was similar, with only one death related to LCIG/device [ 18 ].…”

Pharmacokinetics of Intravenously (DIZ101), Subcutaneously (DIZ102), and Intestinally (LCIG) Infused Levodopa in Advanced Parkinson Disease

“…However, LCIG requires gastric surgery and is associated with considerable risk for device complications. 11 , 13 , 14 …”

“…However, LCIG requires gastric surgery and is associated with considerable risk for device complications. 11,13,14 More practical than intestinal administration would be to use a subcutaneous route, as is currently done with the dopamine agonist apomorphine. Therefore, the purpose of this study was to explore whether a complete and rapid uptake of levodopa from the subcutaneous tissue may be obtained by the administration of a recently developed levodopa (10 mg/mL) plus carbidopa (1.25 mg/mL) solution (DIZ102) consisting of a stock solution where levodopa and carbidopa are dissolved at a low pH brought to a physiologically favorable pH (5.0-5.3) by continuous mixing with a buffer.…”