Levodopa-Carbidopa-Entacapone Intestinal Gel in Advanced Parkinson Disease: A Multicenter Real-Life Experience.

BACKGROUND: For Parkinson disease (PD) patients who have been diagnosed with advanced disease that can no longer be effectively controlled with optimized oral or transdermal medications, a range of device-aided therapies (DAT) are available, comprising either deep brain stimulation or infusion therapies providing continuous dopaminergic stimulation. Levodopa-entacapone-carbidopa intestinal gel (LECIG) infusion is the latest DAT for advanced PD (APD) that was approved in Romania in 2021. STUDY QUESTION: What is the experience to date in real-world clinical practice in Romania regarding the efficacy and tolerability of LECIG in APD? STUDY DESIGN: A retrospective evaluation of 74 APD patients treated with LECIG at 12 specialized APD centers in Romania. MEASURES AND OUTCOMES: Demographic data and various clinical parameters were recorded, including Mini Mental State Evaluation score or Montreal Cognitive Assessment Test score. Levodopa-equivalent daily dose and the administered doses of levodopa and other PD medications were evaluated at baseline and after starting LECIG treatment. The efficacy of LECIG in reducing daily hours of off time, motor fluctuations, and dyskinesias were assessed. Any percutaneous endoscopic gastrojejunostomy system or device complications after starting LECIG treatment were noted. RESULTS: At baseline, patients were taking oral levodopa for a mean of 5.3 times per day, with a high proportion also taking concomitant add-on therapies (dopamine agonists, 86%, monoamine oxidase type-B inhibitors, 53%; catechol-O-methyltransferase inhibitors, 64%). LECIG treatment significantly reduced daily off time versus baseline from 5.7 h/d to 1.7 hours per day ( P < 0.01). Duration and severity of dyskinesias was also significantly reduced versus baseline, and improvements were observed in Hoehn and Yahr Scale scores. LECIG treatment also allowed a significant reduction in the use of concomitant oral medications. CONCLUSIONS: These findings suggest that LECIG treatment is an effective DAT option in APD that can simplify the treatment regimen.

Levodopa-Entacapone-Carbidopa Intestinal Gel in the Treatment of Advanced Parkinson's Disease: A Single Center Real-World Experience.

Levodopa-entacapone-carbidopa intestinal gel infusion is a relatively new treatment option for advanced Parkinson's disease. We aimed to describe and analyze the characteristics of de novo levodopa-entacapone-carbidopa intestinal gel therapy in 20 consecutive patients with advanced Parkinson's disease. We assessed the profile of motor complications by evaluating the following: motor fluctuations, dyskinesias, and the freezing phenomenon at baseline (before the testing period) and before discharge. The treatment significantly reduced the duration of daily hours spent in off time compared with baseline pre-treatment values from a mean of 4.8 ± 0.9 h/day to a mean of 1.4 ± 0.5 h per day (p < 0.001). The duration and severity of peak-dose dyskinesia were also significantly reduced compared with baseline values. Out of the 10 patients who reported freezing, 8 did not present this complication at the pre-discharge assessment. Significant improvements were observed in Hoehn and Yahr scale scores in both the on and off states. The levodopa-entacapone-carbidopa intestinal gel therapy was well tolerated during the follow-up period immediately after initiation. Despite a relatively severe stage of the disease, all patients experienced a significant improvement in motor fluctuations, dyskinesias, and the freezing phenomenon.

Starting with 24-h levodopa carbidopa intestinal gel at initiation in a large cohort of advanced Parkinson's disease patients.

Continuous intra-jejunal infusion of levodopa-carbidopa intestinal gel (LCIG) is a long-term proven and effective treatment in advanced Parkinson's Disease (APD). Efficacy and safety of 16-h administration of LCIG has already been established. Additional benefits of 24-h LCIG administration have been reported in several case series and small clinical studies. The aim of this retrospective study was to compare the characteristics of patients who needed 24-h LCIG from the beginning of the DAT (device-aided treatment) with those who remained with the standard 16-h LCIG treatment and to identify particular motives if any. We initiated LCIG in 150 patients out of which in case of 62 patients (41,3%) due to unsatisfactory initial clinical benefits continuous 24-h LCIG was deemed necessary. Despite the subjective complaints and more severe clinical condition, at baseline evaluation we found statistically significant differences between 16-h LCIG cohort and 24-h LCIG cohort only in case of incidence of freezing (47% vs 65%, p = 0.03) and sudden off (32% vs 48%, p = 0.04). Wake hours/daytime LCIG does not always sufficiently improve the patient's quality of life in some patients due to persistent nighttime troublesome symptoms. Instead of labeling the patient as a non-responder, it is worth trying the 24-h LCIG dosage in a carefully selected group of patients, as there is currently no consensus on reliable criteria that serve the decision in these patients.

Levodopa-Carbidopa Intestinal Gel in Advanced Parkinson's Disease: Observations and Dilemmas after 10 Years of Real-Life Experience.

Advanced Parkinson's disease (APD) cannot be treated efficiently using the classical medications however, in recent decades invasive therapeutical methods were implemented and confirmed as effective. One of these methods makes it possible to continue the levodopa (LD) supplementation as a gel administered directly into the upper intestine. However, there are a number of unanswered questions regarding this method. Therefore, we retrospectively analyzed a 10-year period of selected patients that were treated with levodopa/carbidopa intestinal gel (LCIG). We included all APD patients with motor fluctuations and dyskinesia at presentation. LCIG treatment was started in 150 patients: on average these patients received LD for 10.6 ± 4.4 years with a frequency of 5.2 ± 1.0/day until the introduction of LCIG. The estimated and the real LCIG dose differed significantly (mean: 1309 ± 321 mg vs. 1877 ± 769 mg). The mean duration of LCIG administration was 19.8 ± 3.6 h, but in a number of 62 patients we had to administer it for 24 h, to maximize the therapeutic benefit. A carefully and individually adjusted LCIG treatment improves the quality of life of APD patients, but questions remain unresolved even after treating a large number of patients. It is important to share the ideas and observations based on the real-life experience related to the optimal timing, the appropriate dose and duration of administration of the LCIG.

Advanced Parkinson's Disease Treatment Simplification and Long-Term Outcomes with Levodopa Carbidopa Intestinal Gel: COSMOS Romanian Subanalysis.

The aim of the COmedication Study assessing Mono- and cOmbination therapy with levodopa-carbidopa inteStinal gel (COSMOS) was to assess the use of levodopa/carbidopa intestinal gel (LCIG) as monotherapy in patients with advanced Parkinson's disease (APD) in routine clinical practice. COSMOS was an international observational study with one cross-sectional visit and retrospective data collection. In Romania, 95 adult patients with APD on LCIG treatment for at least 12 months were enrolled and stratified according to their LCIG therapy after 12 months: monotherapy (without any add-on PD medication), monotherapy with night PD medication and LCIG + add-on medication. Compared to the moment of LCIG initiation, the percentage of patients on monotherapy increased at three months after LCIG initiation and remained constant up to 12 months, when 30.5% of the patients were on LCIG monotherapy and 11.6% were on monotherapy with night medication. "Off" time and "On" time with dyskinesia decreased from LCIG initiation to patient visit in all groups. LCIG monotherapy with or without night medication may provide a simplified treatment option for selected APD patients, with long-term efficacy similar to that of LCIG plus add-on medication.

Management Challenges of Severe, Complex Dyskinesia. Data from a Large Cohort of Patients Treated with Levodopa-Carbidopa Intestinal Gel for Advanced Parkinson's Disease.

BACKGROUND: In the advanced stages of Parkinson's disease (APD), complex forms of dyskinesia may severely impair the patient's quality of life. OBJECTIVE: In the present study, we aimed to analyze the evolution under LCIG therapy of the most important motor fluctuations and complex disabling dyskinesias, including diphasic dyskinesia. METHODS: In this retrospective study, we analyzed the characteristics of patients with APD who had at least 30 min of diphasic dyskinesia (DID) in 3 consecutive days, were considered responders and were treated with LCIG in our clinic. Patients were evaluated before and after PEG and at 6, 12 and 18 months, when the changes in the therapy were recorded, and they completed a 7-point Global Patient Impression of Improvement (PGI-I) scale. RESULTS: Forty patients fulfilled the inclusion criteria-out of which, 34 performed all visits. There was a substantial difference between the calculated and real LCIG (1232 ± 337 mg vs. 1823 ± 728 mg). The motor fluctuations and most dyskinesias improved significantly after starting LCIG, but an increasing number of patients needed longer daily administrations of LCIG (24 instead of 16 h). CONCLUSIONS: Patients with APD with complex dyskinesias must be tested in dedicated hospitals, and they need a special therapeutic approach. The properly adapted LCIG treatment regarding the dose and time of administration completed with well-selected add-on medication should offer improvement for patients who want to or can only choose this DAT vs. others.

Characterizing Advanced Parkinson's Disease: Romanian Subanalysis from the OBSERVE-PD Study.

OBSERVE-PD was a cross-sectional, multicountry, observational study conducted in 128 Movement Disorders Centers (MDCs) in 18 countries. Overall, the study enrolled 2615 patients. The aim was to determine the proportion of patients with advanced Parkinson's disease (APD) versus non-APD from MDCs and to uncover the clinical burden of APD, as well as a correlation between overall assessment of APD and several indicators of APD. The advanced stage of the disease and severity were assessed by investigators using their clinical judgement. Data were collected during a single visit between February 2015 and January 2016. Agreement on physician judgement of APD diagnosis and fulfillment of at least one previously established APD indicator was calculated. Motor and nonmotor symptoms (NMSs), activities of daily living, treatment complications, quality of life (QoL), conventional treatments, and device-aided therapy (DAT) eligibility were assessed. Here, country-specific results of 161 Romanian patients with PD are presented. In total, 59.0% of patients were diagnosed with APD and 78.8% met at least one APD indicator. There was only moderate agreement between clinical judgement of APD and overall fulfillment of APD indicators. All scores related to motor symptoms, NMSs, and treatment complications, as well as to QoL, showed a higher disease burden for patients with APD versus non-APD. Physicians considered 73.7% of patients with APD eligible for DAT. The majority of patients eligible for DAT (54.3%) did not receive such treatment. Our results highlight the importance of earlier recognition of APD, by combining clinical judgement with more standardized clinical tools, such as generally recognized APD criteria. However, timely diagnosis of APD alone is not enough to improve patient outcomes. Other critical factors include patient acceptance and access to appropriate treatment.

Levodopa-Carbidopa Intestinal Gel Infusion Therapy Discontinuation: A Ten-Year Retrospective Analysis of 204 Treated Patients.

BACKGROUND: Parkinson's disease (PD) is the second most common progressive neurodegenerative disease. In the advanced stages, the continuous delivery of levodopa (LD) as levodopa-carbidopa intestinal gel (LCIG) has demonstrated significant improvement of motor and nonmotor complications and improvement of the patients' quality of life (QoL). Despite the growing global experience with this treatment, anumber of unsolved practical issues remain, and currently, the data on the reasons that can lead to the discontinuation of LCIG are scarce. OBJECTIVE: In the present study, we aimed to analyze the causes that led to the discontinuation of LCIG therapy. METHODS: In this retrospective study, after 10 years of experience with LCIG as a therapeutic option in advanced PD, we analyzed the data of all dropout cases among the 204 patients that initiated LCIG therapy in two Romanian centers. RESULTS: Of the 204 patients enrolled, 43 patients dropped out. Disease duration until LCIG infusion was significantly longer (11.67±4.98 vs 9.44±3.44) and the overall clinical picture more sever (both regarding motor symptoms and cognitive decline) in dropout patients (compared to patients who continued treatment). The dropout patients also presented significant differences regarding the incidence of polyneuropathy (32.5% vs 11.18%). The main cause of discontinuation was death. CONCLUSION: The causes of discontinuation from LCIG therapy in Romanian patients are similar to those from other centers; however, the rate of dropouts is somewhat lower. The clinician's experience in selecting and treating the patients in advanced stages of PD can increase therapeutic adherence. Also, the presence of a well-trained caregiver along with the availability of a proper aftercare system is mandatory for maintaining the long-term benefits of the therapy and the overall best outcome possible. Targeted prospective studies are needed to confirm whether a more severe stage of the disease and cognitive impairment at the time of initiation, respectively, the association of polyneuropathy can be considered as predictive factors for dropout.

Profile Of Patients With Advanced Parkinson's disease Suitable For Device-Aided Therapies: Restrospective Data Of A Large Cohort Of Romanian Patients.

BACKGROUND: There is insufficient data in the literature regarding the real-life, daily clinical practice evaluation of patients with advanced Parkinson's disease (APD). We are not sure what is the upper limit of dopaminergic medication, especially the levodopa (LD) dosage, and how it is influenced by access and suitability to the various add-on and device-aided therapies (DAT). OBJECTIVE: This retrospective study explored the profile of APD patients that were considered and systematically evaluated regarding the suitability for DAT. METHODS: We analyzed the data from 311 consecutive patients with APD hospitalized between 2011 and 2017 that 1) described at least 2 hrs/day off periods divided into at least two instances/day (except early morning akinesia), 2) were in stage 3 or above on the Hoehn and Yahr scale, 3) were with or without dyskinesia, and 4) received at least four levodopa doses/day combined with adjuvant therapy. RESULTS: Of the 311 patients enrolled initially, 286 patients showed up for the second visit, of which in 125 cases we assessed that DAT would be necessary. Finally, 107 patients were tested in our clinic to confirm the efficacy of LCIG. Patients selected for DAT had significantly longer off periods, more frequent dyskinesia, early morning akinesia, and freezing despite having significantly higher LD doses than those with an improved conservative therapy. CONCLUSION: Patients with APD can have a variety of symptoms, and because symptoms and therapeutical efficacy can be manifested in many different combinations, it is not possible to decide using a single, rigid set of criteria which APD patient is eligible for DAT. Nevertheless, treating physicians should refer APD patients to a specialized movement disorder center when patients with an average daily dose of LD of at least 750-1000 mg and maximal complementary therapies present daily motor complications that significantly reduce the quality of life.

Therapeutic strategies in the early stages of Parkinson's disease: a cross-sectional evaluation of 15 years' experience with a large cohort of Romanian patients.

INTRODUCTION: In patients older than 70 years there is no valid alternative to progressively introduced substitution therapy. The antiparkinsonian drugs introduced in the last decade to treat Parkinson's disease, especially in its early phases, promised a comparable efficacy in reducing symptoms to levodopa. In younger patients and/or patients with mild symptoms we hoped to delay the motor complications by postponing the start of levodopa therapy. While these assumptions may not be true for all patients, probably the most important current challenge is the optimal starting moment of levodopa therapy. The aim of the study was to analyze the therapeutical choices during the early phase of Parkinson's disease in the Neurological Departments of Târgu Mures¸ County Hospital. MATERIALS AND METHODS: We examined data obtained from hospitalized Parkinson's disease patients during a 15-year period. According to the duration of the disease we split the patients into two groups, patients with Parkinson's disease for less than or equal to 5 years and patients with disease duration longer than 5 years, and then analyzed only the former group. RESULTS: During the examined period, 2,379 patients with Parkinson's disease were hospitalized, and 1,237 patients had a disease duration shorter than 5 years. In this group, 18 patients had monoamine oxidase inhibitor monotherapy. Also, 665 patients received dopamine agonists, in 120 cases as monotherapy and in 83 patients associated with monoamine oxidase inhibitors. In 521 patients we found only levodopa treatment. A further 481 patients received combined therapy (levodopa with dopamine agonists and/or monoamine oxidase inhibitors). CONCLUSION: Treatment strategies for the early stages of Parkinson's disease in our group were comparable to results from other studies. However, the authors feel that neurologists should use levodopa-sparing drugs with greater courage. Furthermore, if the clinical context is appropriate, physicians should combine substitution therapy with other antiparkinsonian drugs in order to reduce levodopa doses.