Integrated safety of levodopa‐carbidopa intestinal gel from prospective clinical trials

Abstract

BackgroundContinuous administration of levodopa‐carbidopa intestinal gel (carbidopa‐levodopa enteral suspension) through a percutaneous endoscopic gastrojejunostomy is a treatment option for advanced Parkinson disease (PD) patients with motor fluctuations resistant to standard oral medications. Safety data from 4 prospective studies were integrated to assess the safety of this therapy.MethodsSafety data from 4 studies were summarized using 2 overlapping data sets, permitting the separation of procedure/device–associated (n = 395) from non‐procedure/device adverse events (n = 412).ResultsAt the data cutoff, median exposure to levodopa‐carbidopa intestinal gel was 911 days (range, 1‐1980 days) with 963 total patient‐years of exposure. Procedure/device adverse events occurred in 300 patients (76%), and serious adverse events occurred in 68 (17%); most frequently reported procedure/device adverse events and serious adverse events were complications of device insertion (41% and 8%, respectively) and abdominal pain (36% and 4%, respectively). Non‐procedure/device adverse events occurred in 92% (379), with most frequently reported being insomnia (23%) and falls (23%); 42% (171) had non‐procedure/device serious adverse events, with most frequently reported being pneumonia (5%) and PD symptoms (2%). Adverse events led to discontinuation in 17% (72), most frequently because of complication of device insertion (2.4%). There were 34 treatment‐emergent deaths (8.3%) in the overlapping data sets, 2 of which (0.5%) were considered “possibly related” to the treatment system.ConclusionIn the largest collection of levodopa‐carbidopa intestinal gel safety data from prospective clinical studies, procedure/device events were frequently reported and occasionally life threatening. Most non‐procedure/device events were typical for levodopa treatment and an elderly population. These factors combined with high treatment efficacy led to a relatively low discontinuation rate in advanced PD patients. © 2015 International Parkinson and Movement Disorder Society

An Observational Study of the Effect of Levodopa–Carbidopa Intestinal Gel on Activities of Daily Living and Quality of Life in Advanced Parkinson’s Disease Patients

“…Results from this prospective, multicenter, observational study showed significant improvements in activities of daily living, motor and non-motor symptoms, and quality-of-life scores, with safety results in accord with the known safety profile of LCIG [11, 12, 17]. These results extend current findings, which have focused primarily on the effect of LCIG on motor complications [10–12, 14].…”

Problems related to levodopa‐carbidopa intestinal gel treatment in advanced Parkinson's disease

“…The majority of our patients were satisfied with the infusion during follow‐up. There were, however, numerous tube and stoma complications related to LCIG, as reported previously (Fernandez et al., ; Lang et al., ; Nilsson et al., ).…”

“…Complications with the PEG‐J tube (Devos, ; Fernandez et al., ; Nyholm et al., ) are similar to complications related to PEG for feeding purposes (Schapiro & Edmundowicz, ; Udd et al., ). The risk of peritonitis has varied between zero and 4% (Devos, ; Epstein et al., ; Lang et al., ; Palhagen et al., ), and other serious complications like colonic perforations, gastropleural fistula (Klostermann et al., ) and liver injury (Pickut et al., ), have also been described. In our material, we did not have any peritonitis, nor any need for emergency abdominal surgery due to LCIG complications.…”

Algorithms for the treatment of motor problems in Parkinson's disease

“…Some patients may experience increasing dyskinesias,64 but optimized LCIG infusion may also be used to treat troublesome dyskinesias 65. Safety data from four prospective studies were recently integrated to assess the safety of LCIG infusion after median 911‐day treatment 66. The most frequently reported procedure/device adverse events were complications of device insertion and abdominal pain, considered serious in 17% of the patients.…”