Long-term safety and efficacy of levodopa-carbidopa intestinal gel in advanced Parkinson's disease.

BACKGROUND: Levodopa-carbidopa intestinal gel (designated as carbidopa-levodopa enteral suspension in the United States) provides stable plasma levodopa concentrations and reduces motor fluctuations in advanced Parkinson's disease patients through continuous delivery of levodopa via percutaneous endoscopic gastrojejunostomy. We report long-term safety and efficacy outcomes from an open-label phase 3 treatment program. METHODS: PD patients (n = 262) who completed a 12-week double-blind study and its 52-week open-label extension or a separate 54-week open-label study were enrolled in this ongoing phase 3 open-label, multinational study (NCT00660673). Safety and efficacy assessments were collected every 6 months. RESULTS: Mean total duration of exposure to levodopa-carbidopa intestinal gel was 4.1 years (range, 1.2 to 6.9 years). The overall discontinuation rate was 34% (average annual discontinuation rate, 10%). Although most patients (94%) reported an adverse event, the rate of adverse events decreased over time; 53% experienced a serious adverse event. Of patients in this extension study, 54% required jejunal tube replacement during the study, and 37% required percutaneous endoscopic gastrostomy tube replacement. Most patients were on levodopa monotherapy. Patients maintained reductions in "off" time and increases in mean "on" time without dyskinesia from initial levodopa-carbidopa intestinal gel infusion to he study end point (P < 0.001; n = 81). Activities of daily living and quality-of-life assessments demonstrated significant improvements that persisted through the study. CONCLUSIONS: This long-term study demonstrates sustained and clinically meaningful benefits from levodopa-carbidopa intestinal gel in advanced PD patients. Although adverse event rates decreased over time, vigilance is required for device-related complications and adverse events. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Long-Term PEG-J Tube Safety in Patients With Advanced Parkinson's Disease.

OBJECTIVES: The objectives of this study were to present procedure- and device-associated adverse events (AEs) identified with long-term drug delivery via percutaneous endoscopic gastrojejunostomy (PEG-J). Levodopa-carbidopa intestinal gel (LCIG, also known in US as carbidopa-levodopa enteral suspension, CLES) is continuously infused directly to the proximal small intestine via PEG-J in patients with advanced Parkinson's disease (PD) to overcome slow and erratic gastric emptying and treat motor fluctuations that are not adequately controlled by oral or other pharmacological therapy. METHODS: An independent adjudication committee of three experienced (>25 years each) gastroenterologists reviewed gastrointestinal procedure- and device-associated AEs reported for PD patients (total n=395) enrolled in phase 3 LCIG studies. The rate, clinical significance, and causality of the procedure/device events were determined. RESULTS: The patient median exposure to PEG-J at the data cutoff was 480 days. Procedure- and device-associated serious AEs (SAEs) occurred in 67 (17%) patients. A total of 42% of SAEs occurred during the first 4 weeks following PEG-J placement. SAEs of major clinical significance with the highest procedural incidence were peritonitis (1.5%), pneumonia (1.5%), and abdominal pain (1.3%). The most common non-serious procedure- and device-associated AEs were abdominal pain (31%), post-operative wound infection (20%), and procedural pain (23%). In all, 17 (4.3%) patients discontinued treatment owing to an AE. CONCLUSIONS: In conclusion, incidences of PEG-J AEs with the LCIG delivery system and PEG-J longevity were compared favorably with ranges described in the PEG/PEG-J literature. A low discontinuation rate in this study suggests acceptable procedural outcomes and AE rates in PD patients treated with this PEG-J drug delivery system.

Patient anxiety and elective gastrointestinal endoscopy.

BACKGROUND: Esophagogastroduodenoscopy (EGD) and colonoscopy (CS) are commonly performed procedures that can cause anxiety related to potential findings, embarrassment and concern over discomfort. The objective of this study is to evaluate patient anxiety associated with diagnostic, sedated outpatient endoscopy and to correlate endoscopists' estimations of patient anxiety with those of the patient. METHODS: Consecutive patients referred for diagnostic upper endoscopy or colonoscopy were evaluated. Anxiety was rated at baseline and immediately before the procedure using the State-Trait Anxiety Index (STAI-Y). Patients were categorized as whether they had been previously seen by a gastroenterologist in the clinic or were referred directly by another physician for endoscopy. Patients were also asked to rate their knowledge of the procedure using a visual analog scale. Physicians rated patient anxiety and procedure difficulty using 100 mm visual analog scales. Sedation administered during each procedure was recorded. RESULTS: Ninety-four patients were enrolled; 47 had been referred from the gastroenterology clinic and 47 had been directly referred from primary care physicians. Thirty-nine percent completed baseline and pre-procedure STAI-Y. Endoscopy was associated with a significant increase in state anxiety (baseline, 31.2 +/- 1.8; procedure, 39.8 +/- 2.2; P = 0.001) but not trait anxiety (baseline, 35.4 +/- 1.7; procedure, 36.2 +/- 1.6; P = 0.59). Procedural state anxiety was not influenced by age, sex, referral source, type of procedure or perceived procedural knowledge but was correlated with trait anxiety (r = 0.38; P = 0.02). Physician estimates of patient anxiety did not correlate with either procedural state anxiety (r = -0.15; P = 0.37) or the change in state anxiety from baseline to the procedure (r = -0.04; P = 0.82). CONCLUSIONS: Diagnostic outpatient endoscopy is associated with modest increases in state anxiety that are not significantly influenced by age, sex, procedure type, indication, or referral source. Endoscopists' ability to estimate patient anxiety is poor but this may reflect the generally mild increases in state anxiety that were encountered.