How Do I Manage Patients With the Levodopa/Carbidopa Intestinal Gel?
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ABSTRACT:
SUBMITTER: Vijiaratnam N
PROVIDER: S-EPMC6384179 | biostudies-literature | 2019 Feb
REPOSITORIES: biostudies-literature
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How Do I Manage Patients With the Levodopa/Carbidopa Intestinal Gel?
Vijiaratnam Nirosen N Sue Carolyn M CM
Movement disorders clinical practice 20181115 2
The levodopa carbidopa intestinal gel is a device-assisted therapy used for the management of fluctuating motor symptoms of Parkinson's disease that are refractory to oral therapy. The approach has demonstrable clinical value, but consideration of the associated need for expert care, access to services, and costs of the treatment impact the method of introduction to optimize uptake and minimize discontinuation across populations examined. Systematic approaches and modifications have been explore ...[more]
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| S-EPMC7396832 | biostudies-literature
Project description:Levodopa-carbidopa intestinal gel (LCIG, carbidopa-levodopa enteral suspension in the United States) is a treatment option for advanced Parkinson's disease (PD) patients with motor fluctuations. The objective of this investigation was to identify the baseline characteristics predictive of treatment response, measured by improvement in motor symptom severity, in advanced PD patients treated with LCIG during a 54-week, open-label phase 3 study. Patients with ?1?h improvement from baseline in "Off" time were categorized as "Responders"; whereas those with <1?h improvement, any worsening, or no post-baseline assessment were "Non-Responders". A subgroup of Responders with ?3?h improvement in "Off" time was also examined; this subgroup was identified as "Robust Responders". Baseline demographics and disease characteristics were analyzed and their predictive relationship to change from baseline in normalized "Off" time was assessed. Out of the 324 patients included in the analysis, 272 (84.0%) were categorized as Responders and 52 (16.0%) were Non-Responders. A majority of patients (65.7%) had ?3?h improvement in "Off" time. In general, baseline characteristics were similar between Non-responders, Responders, and the subgroup of Robust Responders. A conditional tree-structured regression analysis identified baseline "Off" time as the only factor that had significant effect on Responder and Robust Responder status. The safety profile of LCIG was similar between patient groups. Overall, this analysis showed that 84% of LCIG-treated advanced PD patients had ?1?h improvement in "Off" time and the number-needed-to-treat to observe one patient responder was 1.19 patients. Notably, Responders and Robust Responders to LCIG were observed across the range of baseline demographics and clinical characteristics examined.
| S-EPMC5784118 | biostudies-literature
Project description:ObjectiveThe purpose of this study was to assess the effect of levodopa-carbidopa intestinal gel (carbidopa-levodopa enteral suspension) in advanced Parkinson's disease patients with troublesome dyskinesia.MethodsPost hoc analyses of patient data from a 12-week, randomized, double-blind study and a 54-week open-label study were performed. Efficacy was assessed in the subgroup of patients defined by ?1 hour of "on" time with troublesome dyskinesia at baseline as recorded in Parkinson's disease symptom diaries (double blind: n?=?11 levodopa-carbidopa intestinal gel, n?=?12 oral levodopa-carbidopa; open label: n?=?144 levodopa-carbidopa intestinal gel). The changes in "off" time, "on" time with and without troublesome dyskinesia, and the overall safety and tolerability of levodopa-carbidopa intestinal gel were analyzed.ResultsAlthough not significantly different from oral levodopa treatment (P?>?.05) in the double-blind study, levodopa-carbidopa intestinal gel treatment resulted in a reduction from baseline in "on" time with troublesome dyskinesia (mean [standard deviation] hours: baseline?=?3.1 [1.7], change from baseline to final?=?-1.8 [1.8], P?=?.014), increase in "on" time without troublesome dyskinesia (baseline?=?7.4 [2.2], change?=?4.4 [3.6], P?=?.004), and decrease in "off" time (baseline?=?5.5 [1.3], change?=?-2.7 [2.8], P?=?.015). Similar trends were found in the open-label study. An increase in levodopa-carbidopa intestinal gel dose was not significantly correlated with increased "on" time with troublesome dyskinesia in either study (double blind: r?=?-.073, P?=?.842; open label: r?=?-0.001, P?=?.992). Adverse events were usually mild to moderate in severity and related to the gastrointestinal procedure.ConclusionOur exploratory analyses suggest that optimizing levodopa delivery with levodopa-carbidopa intestinal gel may reduce troublesome dyskinesia in advanced Parkinson's disease.
| S-EPMC5066747 | biostudies-literature
Project description:Levodopa-carbidopa intestinal gel (LCIG) infusion has demonstrated to improve motor fluctuations. The aim of this study is to assess the long-term safety and effectiveness of LCIG infusion in advanced Parkinson's disease (PD) patients with motor fluctuations and its effect in nonmotor symptoms.Adverse events (AE) and their management, clinical motor, and nonmotor aspects were assessed up to 10 years. Thirty-seven patients were treated with LGIC; in three subsets of patients, specific batteries of tests were used to assess cognitive and behavior assessment for 6 months, quality of sleep for 6 months, and quality of life and caregiver burden for 1 year.There was a high number of AE, but manageable, most of mild and moderate severity. All patients experienced significant improvement in motor fluctuations with a reduction in mean daily off time of 4.87 hr after 3 months (n = 37) to 6.25 hr after 9 years (n = 2). Diskynesias remained stables in 28 patients (75.7%) and improved in 5 patients (13.5%). There was no neuropsychological deterioration, but an improvement in attentional functions, voluntary motor control, and semantic fluency. Quality of sleep did not worsen, and there was an improvement in the subjective parameters, although overnight polysomnography did not change. There was a significant sustained improvement of 37% in PD-Q39 after 3 months and to 1 year, and a significant reduction in caregiver burden of 10% after 3 months.LCIG infusion is a safe and efficacious treatment for the control of motor fluctuations, and for improvement or nonworsening of nonmotor aspects, long-term sustained, and feasible for use in routine care.
| S-EPMC5561319 | biostudies-other
Project description:Background:Gait and balance disorders in advanced Parkinson's disease (aPD) heavily impact the disease burden. In this prospective observational open-label study, our aim was to evaluate the effectiveness of levodopa/carbidopa intestinal gel (LCIG) infusion on balance and gait over a long-term follow-up. Methods:The motor status of 15 aPD patients with balance and gait symptoms was assessed with UPDRS (I-IV) and H&Y at baseline in OFF and ON conditions, and after 52 weeks of LCIG infusion. Berg Balance Scale (BBS), Tinetti Gait & Balance Score (TS), Gait and Falls Questionnaire (G&F-Q), FOG Questionnaire (FOG-Q), and New FOG Questionnaire (NFOG-Q) were used to specifically test balance and gait. Results:UPDRS, H&Y, BBS, TS, G&F-Q, FOG-Q, NFOG-Q improved significantly. All FOG types benefited from LCIG. Conclusions:Our preliminary data show the beneficial effect of LCIG therapy not only on FOG, but also on gait and balance. Results need to be confirmed in larger cohort studies.
| S-EPMC6207104 | biostudies-literature
Project description:BackgroundContinuous delivery of levodopa-carbidopa intestinal gel (LCIG) provides stable plasma levodopa concentrations and reduces motor fluctuations in advanced Parkinson's disease (PD) patients.ObjectiveTo compare the effectiveness and safety of LCIG monotherapy vs polytherapy in patients in the GLORIA registry.MethodsThis was a post hoc analysis of a 24-month, multinational observational registry where advanced PD patients with persistent motor complications received LCIG (with adjunctive PD treatment, as necessary). Patients were categorized retrospectively into three stable treatment groups: LCIG monotherapy, LCIG in combination with oral levodopa only ("levodopa monotherapy" [including nighttime oral levodopa]), or LCIG in combination with any other antiparkinsonian medication ("LCIG polytherapy").ResultsOf 356 patients, 208 were on stable regimens (LCIG monotherapy n?=?80; levodopa monotherapy n?=?47; LCIG polytherapy n?=?81). Baseline characteristics were similar across groups. LCIG monotherapy showed significant improvements until month 18 in activities of daily living and quality of life, and until month 24 for Unified Parkinson's Disease Rating Scale (UPDRS) motor examination (p?<?0.05), "Off" time (p?<?0.001), "On" time with dyskinesia (p?<?0.01), and non-motor symptoms (p?<?0.01). More patients in the levodopa monotherapy and LCIG polytherapy groups experienced treatment-related adverse drug reactions (ADRs) including dyskinesias and serious ADRs than did patients in the LCIG monotherapy group. There were few polyneuropathy-related ADRs, of which one case of polyneuropathy led to discontinuation from the Levodopa monotherapy group.ConclusionsThese data demonstrate that LCIG monotherapy is an effective treatment option in appropriate advanced PD patients; however, definitive baseline clinical predictors identifying patients who can discontinue concomitant oral therapy have not yet been defined.
| S-EPMC6700622 | biostudies-literature
Project description: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.
| S-EPMC5064722 | biostudies-literature
Project description:BackgroundLevodopa-carbidopa intestinal gel (LCIG, designated in the United States as carbidopa-levodopa enteral suspension, CLES) was approved in the United States in 2015 for the treatment of refractory motor fluctuations in individuals with Parkinson disease (PD). Many neurologists in the United States have not had personal experience with implementation and management of the unique delivery system for this treatment.Methods and findingsThis educational review was developed to provide practitioners with an understanding of LCIG use from the clinician's point of view. Practical recommendations for the use of LCIG from the early planning stages through long-term patient management were compiled from the published literature, regulatory guidance, and clinical experience. Among the topics reviewed were: assembling a multidisciplinary treatment team, identifying treatment candidates, patient/care partner education, procedural considerations, post-procedural care, LCIG initiation and titration, troubleshooting issues, and ongoing monitoring. For most of these steps, a considerable amount of individualization is possible, which allows clinicians to tailor protocols based on the needs of their teams, the healthcare system, and the patient and care partner. Although clinical practices are heterogeneous, themes of early planning, ongoing education, and a team-based approach to management are universal.ConclusionsBy using established protocols and insights gleaned from experienced practitioners, clinicians who are unfamiliar with LCIG can more feasibly incorporate this treatment option into their armamentarium for treating PD motor fluctuations.
| S-EPMC6174493 | biostudies-literature
Project description:BackgroundLevodopa-carbidopa intestinal gel (LCIG; carbidopa-levodopa enteral suspension in the United States), delivered via percutaneous gastrojejunostomy (PEG-J) and titrated in the inpatient setting, is an established treatment option for advanced Parkinson's disease (PD) patients with motor fluctuations. However, long-term prospective data on the efficacy of LCIG on non-motor symptoms and the safety of outpatient titration are limited.MethodsIn this 60-week, open-label phase 3b study, LCIG titration was initiated in an outpatient setting following PEG-J placement in PD patients. The efficacy of LCIG on motor and non-motor symptoms, quality of life, and safety was assessed.ResultsThirty-nine patients were enrolled in the study and 28 patients completed the treatment. A majority of patients (54%) completed outpatient titration within the first week of LCIG infusion. LCIG led to significant reductions from baseline in Non-Motor Symptom Scale (NMSS) total score (least squares mean ± SE = -17.6 ± 3.6, P < 0.001) and 6 of the NMSS domain scores (sleep/fatigue, attention/memory, gastrointestinal tract, urinary, sexual function, miscellaneous) at week 12. These reductions were maintained at week 60 with the exception of the urinary domain. "Off" time (-4.9 ± 0.5 hours/day, P < 0.001) and "On" time without troublesome dyskinesia (-4.3 ± 0.6 hours/day, P < 0.001) were improved at week 60. Adverse events (AEs) were reported in 37 (95%) patients.ConclusionsLCIG treatment led to reductions in non-motor symptom burden and motor fluctuations in advanced PD patients. The safety profile was consistent with previous studies that used inpatient titration and outpatient titration did not appear to pose additional risk.
| S-EPMC5724683 | biostudies-literature
Project description:Levodopa-carbidopa intestinal gel (LCIG) delivered continuously via percutaneous endoscopic gastrojejunostomy (PEG-J) tube has been reported, mainly in small open-label studies, to significantly alleviate motor complications in Parkinson's disease (PD). A prospective open-label, 54-week, international study of LCIG is ongoing in advanced PD patients experiencing motor fluctuations despite optimized pharmacologic therapy. Pre-planned interim analyses were conducted on all enrolled patients (n = 192) who had their PEG-J tube inserted at least 12 weeks before data cutoff (July 30, 2010). Outcomes include the 24-h patient diary of motor fluctuations, Unified Parkinson's Disease Rating Scale (UPDRS), Clinical Global Impression-Improvement (CGI-I), Parkinson's Disease Questionnaire (PDQ-39), and safety evaluations. Patients (average PD duration 12.4 yrs) were taking at least one PD medication at baseline. The mean (±SD) exposure to LCIG was 256.7 (±126.0) days. Baseline mean "Off" time was 6.7 h/day. "Off" time was reduced by a mean of 3.9 (±3.2) h/day and "On" time without troublesome dyskinesia was increased by 4.6 (±3.5) h/day at Week 12 compared to baseline. For the 168 patients (87.5%) reporting any adverse event (AE), the most common were abdominal pain (30.7%), complication of device insertion (21.4%), and procedural pain (17.7%). Serious AEs occurred in 60 (31.3%) patients. Twenty-four (12.5%) patients discontinued, including 14 (7.3%) due to AEs. Four (2.1%) patients died (none deemed related to LCIG). Interim results from this advanced PD cohort demonstrate that LCIG produced meaningful clinical improvements. LCIG was generally well-tolerated; however, device and procedural complications, while generally of mild severity, were common.
| S-EPMC3661282 | biostudies-literature