AIM OF STUDY: To determine whether a high dose of levodopa-carbidopa intestinal gel (LCIG), expressed as levodopa equivalent daily dose (LE daily dose), is a risk factor for acute polyneuropathy in patients treated with LCIG. CLINICAL RATIONALE FOR STUDY: Treatment with LCIG is an effective device-assisted therapy in the advanced stages of Parkinson's Disease (PD). Polyneuropathy is a well-known complication of PD treatment. Patients treated with oral levodopa usually suffer from sub-clinical or mild chronic sensory polyneuropathy. However, severe acute polyneuropathy occurs in patients treated with LCIG, which is causally related to the treatment and leads to its immediate discontinuation. The etiology is not yet clear, but some patients with acute polyneuropathy have been given high doses of LCIG. MATERIAL AND METHODS: A retrospective multicentre study of patients treated with LCIG was performed. Patients with acute polyneuropathy were subjected to a detailed analysis including statistical processing. RESULTS: Of 183 patients treated with LCIG in seven centres, six patients (five females, median age 63 years) developed acute polyneuropathy with LCIG discontinuation. The median (interquartile range) initial and final LE daily dose in patients with and without acute polyneuropathy was 3,015 (2,695-3,184) and 1,898 (1,484-2,167) mg, respectively. The final LE daily dose of 2,605 mg cut-off had 83% sensitivity and 93% specificity for the prediction of acute polyneuropathy. CONCLUSIONS AND CLINICAL IMPLICATIONS: The risk of acute polyneuropathy in LCIG-treated patients was associated with a daily LE dose of greater than 2,605 mg or with more than a 62% increase in the daily LE dose during LCIG treatment.
- MeSH
- antiparkinsonika * škodlivé účinky aplikace a dávkování MeSH
- fixní kombinace léků * MeSH
- gely * MeSH
- karbidopa * aplikace a dávkování škodlivé účinky MeSH
- levodopa * aplikace a dávkování škodlivé účinky MeSH
- lidé středního věku MeSH
- lidé MeSH
- Parkinsonova nemoc * farmakoterapie MeSH
- polyneuropatie * chemicky indukované farmakoterapie MeSH
- retrospektivní studie MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
Cieľom štúdie bolo poukázať na prínos nových invazívnych terapeutických postupov v liečbe pokročilých štádií Parkinsonovej choroby (PCh) v porovnaní s klasickou perorálnou farmakoterapiou. Výsledky boli získané zo súboru 43 pacientov s PCh, z ktorých 39 % podstúpilo klasickú terapiu pozostávajúcu z perorálnych antiparkinsoník, 23 % pacientov užívalo intestinálny gél obsahujúci levodopou (Duodopa), 19 % pacientov malo indikovanú apomorfínovú subkutánnu pumpu a 19 % pacientov podstúpilo hĺbkovú mozgovú stimuláciu (DBS). Väčšina pacientov mala pokročilejšie štádiá PCh, štádium 4 podľa Hoehnovej a Yahra (1967). Výsledky práce ukazujú zlepšenie stavu po nasadení nového terapeutického postupu u väčšiny pacientov v porovnaní s klasickou terapiou. Pozitívny vplyv bol zaznamenaný aj v zníženej potrebe užívania liekov per os, kde bol zaznamenaný signifikantný pokles pri všetkých nových terapeutických postupoch. Taktiež bol zaznamenaný pozitívny účinok v redukcii off stavov u pacientov. V prípade Duodopy a DBS došlo k skráteniu off periódy o 50 % a pri apomorfínovej pumpe o 40 %. Pacienti tiež hlásili zlepšenie niektorých symptómov ochorenia ako tremor či rigidita, zatiaľ čo dyskinézy naďalej predstavujú výzvu. Na základe získaných výsledkov sa môže konštatovať, že nové terapeutické postupy pri PCh umožnia zvládnuť symptómy typické pre pokročilé štádia ochorenia, ktoré by bez týchto postupov viedli k invalidite, čo je hlavným dôvodom ich indikácie. U pacientov s pomalšou progresiou ochorenia v skorých štádiách je klasická forma terapie perorálnymi antiparkinsonikami stále zlatým štandardom. Dôvodom je nielen ich relatívna účinnosť, ale aj lepšia ekonomická dostupnosť, nakoľko nové postupy sú spojené s vysokými finančnými nákladmi a v rámci verejného zdravotného poistenia môžu byť v Slovenskej republike použité len na základe rozhodnutia revízneho lekára.
The aim of the study was to point out the contribution of new invasive therapeutic procedures in the treatment of advanced stages of Parkinson’s disease (PD) in comparison with classical oral pharmacotherapy. Data originated from a group of 43 patients with PD, 39% (17) with classic treatment, 23% (10) with intestinal gel of methyl ester levodopa (Duodopa), 19% (8) of patients were using subcutaneous delivery of apomorphine (APO) and the same quantity of patients had undergone deep brain stimulation (DBS). Majority of patients had advanced stages of PD, stage 4, by standards of Hoehn and Yahr scale (Hoehn and Yahr, 1967). Research observed improvement in majority of patients with novel treatments. A positive effect was also noted in the reduced need for oral therapy, where there was a significant decrease in all new therapies. Benefits were observed in the amount of antiparkinsonic drugs taken per os, where we observed reduction in all new therapies. A positive effect of the new therapeutic approaches in reducing “off” periods in patients has also been noted. In the case of Duodopa and DBS, the ”off” period was shortened up to 50% and in the apomorphine pump up to 40%. Patients also reported reduction of some symptoms like rigidity, tremor and bradykinesis while dyskinesis still remains suba challenge. On the basis of the obtained results, it can be concluded that new therapeutic procedures for PCh will make it possible to manage symptoms typical of advanced stages of the disease, which without these procedures would lead to disability, which is the main reason for their indication. However, in early stages, well responding patients or in slow progressing disease oral antiparkinsonics are remaining as golden standard of treatment. This is not just due to good response but also because these classic drug formulations are significantly less expensive. In Slovakia, novel treatments are accessible through healthcare insurance only after secondary revision by insurance company doctors.
- Klíčová slova
- Duodopa, apomorfínová pumpa,
- MeSH
- apomorfin aplikace a dávkování terapeutické užití MeSH
- fixní kombinace léků MeSH
- hluboká mozková stimulace metody MeSH
- implantabilní infuzní pumpy MeSH
- karbidopa farmakologie terapeutické užití MeSH
- klinická studie jako téma MeSH
- levodopa farmakologie terapeutické užití MeSH
- lidé MeSH
- Parkinsonova nemoc * terapie MeSH
- Check Tag
- lidé MeSH
BACKGROUND: While immediate benefits of levodopa-carbidopa intestinal gel (LCIG) are evident in patients with Parkinson's disease (PD), long-term LCIG effects require further study. OBJECTIVES: We explored long-term LCIG on motor symptoms, nonmotor symptoms (NMS), and LCIG treatment settings in patients with advanced PD (APD). METHODS: Data were obtained (medical records and patient visit) from COSMOS, a multinational, retrospective, cross-sectional post-marketing observational study in patients with APD. Patients were stratified into 5 groups based on LCIG treatment duration at the patient visit, from 1-2 to > 5 years LCIG. Between-group differences were assessed for changes from baseline in LCIG settings, motor symptoms, NMS, add-on medications, and safety. RESULTS: Out of 387 patients, the number of patients per LCIG group was: > 1- ≤ 2 years LCIG (n = 156); > 2- ≤ 3 years LCIG (n = 80); > 3- ≤ 4 years LCIG (n = 61); > 4- ≤ 5 years LCIG (n = 30); > 5 years LCIG (n = 60). Baseline values were similar; data reported are changes from the baseline. There were reductions in "off" time, dyskinesia duration, and severity across LCIG groups. Prevalence, severity, and frequency of many individual motor symptoms and some NMS were reduced amongst all LCIG groups, with few differences between groups. Doses for LCIG, LEDD and LEDD for add-on medications were similar across groups both at LCIG initiation and patient visit. Adverse events were similar across all LCIG groups and consistent with the established safety profile of LCIG. CONCLUSIONS: LCIG may provide sustained, long-term symptom control, while potentially avoiding increases in add-on medication dosages. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03362879. Number and date: P16-831, November 30, 2017.
- MeSH
- antiparkinsonika škodlivé účinky MeSH
- fixní kombinace léků MeSH
- gely terapeutické užití MeSH
- karbidopa * MeSH
- levodopa terapeutické užití MeSH
- lidé MeSH
- Parkinsonova nemoc * farmakoterapie MeSH
- průřezové studie MeSH
- retrospektivní studie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
- Klíčová slova
- LECIGIMON,
- MeSH
- antiparkinsonika terapeutické užití MeSH
- gastrointestinální intubace metody MeSH
- gely MeSH
- karbidopa aplikace a dávkování farmakokinetika MeSH
- katecholy aplikace a dávkování farmakokinetika MeSH
- kombinovaná farmakoterapie MeSH
- levodopa aplikace a dávkování farmakokinetika MeSH
- lidé MeSH
- nitrily aplikace a dávkování farmakokinetika MeSH
- Parkinsonova nemoc farmakoterapie patofyziologie MeSH
- stupeň závažnosti nemoci MeSH
- Check Tag
- lidé MeSH
BACKGROUND: Levodopa-carbidopa intestinal gel (LCIG) is administered directly to the small intestine of patients with advanced Parkinson's disease (APD) to help maintain stable plasma levodopa levels. OBJECTIVE: The objective of this study was to investigate the effect of LCIG in reducing polypharmacy for the treatment of APD. METHODS: The COmedication Study assessing Mono- and cOmbination therapy with levodopa-carbidopa inteStinal gel (COSMOS) is a large, real-world, multinational observational study investigating comedication use with LCIG. All enrolled patients had used LCIG for ≥12 months and data were collected cross-sectionally (study visit) and retrospectively. The primary endpoint was the percentage of patients using LCIG as monotherapy (without add-on PD medications) at initiation and at 3, 6, 9, and 12 months thereafter. RESULTS: Overall, 409 patients were enrolled from 14 countries and were treated with LCIG for a mean of 35.8 ± 23.2 months. A total of 15.2% of patients initiated LCIG as monotherapy and 31.7% were receiving monotherapy at 12 months after initiation. The mean duration of LCIG monotherapy was 39.3 ± 25.6 months. Use of add-on medications decreased over time with all LCIG regimens. From LCIG initiation to the patient visit, mean off time decreased by 3.8, 4.6, and 3.9 hours/day for LCIG monotherapy, LCIG daytime monotherapy, and LCIG polytherapy groups, respectively, while duration of dyskinesia decreased by 1.7, 2.0, and 1.9 hours/day, respectively. Adverse events likely related to study treatment occurred in 112 patients (27.4%) during LCIG treatment. CONCLUSIONS: LCIG is an effective long-term monotherapy option with a positive risk-benefit profile and contributes to reduced polypharmacy for patients with APD. © 2021 The AbbVie Inc. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
LCIG je účinnou liečbou pokročilého štádia Parkinsonovej choroby. Jednou z obávaných komplikácii tejto liečby je polyneuropatia, ktorá môže zásadne ovplyvniť motorické aj non-motorické funkcie pacienta a kvalitu jeho života. Vo väčšine prípadov ide o metabolicky podmienenú polyneuropatiu v dôsledku užívania levodopy, a tým spojenej elevácie homocysteínu a deficitu vitamínov skupiny B. V prípade výskytu akútnej polyneuropatie je potrebné vylúčiť Guillainov-Barrého syndróm a ukončiť liečbu LCIG. U každého pacienta by sa malo myslieť na uvedenú komplikáciu, a to už pred zvažovanou indikáciou a následne aj počas celej doby liečby LCIG.
LCIG is an effective treatment for the advanced stage of Parkinson's disease. Serious complication of this treatment is polyneuropathy, which can signifficantly influenced motor and non-motor functions of the patient and the quality of life. In most of the cases there is a metabolic cause of polyneuropathy due to the usage of levodopa, associated with elevation of homocysteine and deficiency of vitamins B. In case of acute polyneuropathy, it is necessary to exclude Guillain-Barré Syndrome and discontinue LCIG treatment. Each patient should be examined for polyneuropathy before the initiation of LCIG therapy and also during the treatment.
- MeSH
- diferenciální diagnóza MeSH
- fixní kombinace léků MeSH
- gely terapeutické užití MeSH
- Guillainův-Barrého syndrom diagnóza MeSH
- homocystein metabolismus MeSH
- karbidopa terapeutické užití MeSH
- levodopa terapeutické užití MeSH
- lidé MeSH
- Parkinsonova nemoc farmakoterapie komplikace MeSH
- polyneuropatie * chemicky indukované diagnóza farmakoterapie klasifikace prevence a kontrola MeSH
- pyridoxin aplikace a dávkování MeSH
- vitamin B 12 aplikace a dávkování MeSH
- vitaminy metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Parkinsonova choroba patrí aj v dnešnej dobe k vážnym neurologickým ochoreniam, pri ktorých neexistuje žiadna prevencia a aktuálne ich nevieme ani vyliečiť. Výrazne zasahuje do každodenného života pacientov a znižuje kvalitu ich života. Vďaka liečbe duodenálnym gélom je však možné udržiavať príznaky ochorenia pod kontrolou v priebehu dňa. Táto liečba smeruje k maximálnemu možnému zmierneniu príznakov ochorenia, ale aj k prevencii výskytu komplikácií, ktoré so sebou ochorenie prináša. Pacientom sa vďaka liečbe zvyšuje dyskomfort a súčasne sa znižuje miera odkázanosti na pomoc okolia. Pre pacienta je táto pomoc neoceniteľná.
Up to this day, the Parkinson’s disease is still a serious neurological condition without existence of any kind of prevention and it is not possible to cure it right now. It’s significantly affecting everyday living and decreasing quality of the patient’s life. Thanks to the duodenal gel treatment it’s possible to maintain the disease symptoms under day control. This treatment heads towards maximal possible reduction of the symptoms, but also to prevent the occurrence of complications. Patient’s discomfort and the dependency rate on surroundings is reduced by this treatment. For the patient, this help is invaluable
Pokročilé štádiá Parkinsonovej choroby sú sprevádzané širokou škálou motorických i nemotorických komplikácií, ktoré závažnou mierou negatívne vplývajú na kvalitu života pacientov. Terapeutické ovplyvnenie týchto komplikácii, ktoré nielen vyplývajú z neurodegeneratívnej povahy základného ochorenia, ale sú podmienené i dlhodobým užívaním dopaminergnej liečby, predstavuje v klinickej praxi závažný problém. Liečebná stratégia sa v poslednom období upriamuje na zabezpečenie kontinuálnej dopaminergnej stimulácie, cieľom ktorej je dosiahnuť vyrovnanú kontrolu symptómov. S progresiou ochorenia a liekmi indukovaných komplikácií konvenčné farmakologické postupy často v tomto smere zlyhávajú. Do popredia terapeutického záujmu sa dostávajú iné, alternatívne spôsoby liečby, ktoré zohrávajú dôležitú úlohu pri liečbe prejavov Parkinsonovej choroby u pacientov v pokročilých štádiách ochorenia. Medzi tieto postupy patrí hĺbková mozgová stimulácia, subkutánne kontinuálne podávanie apomorfínu a liečba intestinálnym gélom levodopa/carbidopa. Správna selekcia pacientov, zohľadnenie prítomnosti špecifických nemotorických symptómov a potenciálnych rizík sprevádzajúcich jednotlivé liečebné modality sa významnou mieru podieľa na výbere najvhodnejšieho postupu.
Advanced stages of Parkinson‘s disease are accompanied by a broad scale of motor and non-motor complications which negatively impact patients' quality of life. The therapeutic influence of these complications resulting from the neurodegenerative nature of the underlying disease and are additionally caused by long-term use of dopaminergic treatment, represents a serious clinical problem. Recently, the therapeutic strategy has been focused on continuous dopaminergic stimulation to achieve the balanced control of symptoms. With disease progression and drug-induced complications conventional pharmacological procedures often fail to control clinical symptoms. Alternative methods rise to the forefront of therapeutic interest as they play an important role in the treatment of advanced Parkinson‘s disease. These options include: deep brain stimulation, subcutaneous application of apomorphine and levodopa/carbidopa intestinal gel therapy. Correct patient selection, consideration of specific non-motor symptoms and potential risks accompanying individual treatment modalities, significantly contribute to the selection of most appropriate procedure.
- MeSH
- apomorfin farmakologie terapeutické užití MeSH
- hluboká mozková stimulace metody využití MeSH
- karbidopa farmakologie terapeutické užití MeSH
- levodopa farmakologie terapeutické užití MeSH
- lidé MeSH
- motorické poruchy MeSH
- parenterální infuze metody MeSH
- Parkinsonova nemoc * komplikace terapie MeSH
- podkožní absorpce MeSH
- Check Tag
- lidé MeSH
INTRODUCTION: This registry evaluated the 24-month safety and efficacy of levodopa-carbidopa intestinal gel (LCIG) treatment in advanced Parkinson's disease (PD) patients under routine clinical care. METHODS: Motor fluctuations, dyskinesia, non-motor symptoms, quality of life, and safety were evaluated. Observations were fully prospective for treatment-naïve patients (60% of patients) and partially retrospective for patients with ≤12 months of pre-treatment with LCIG (40% of patients). Hours of "On" and "Off" time were assessed with a modified version of the Unified Parkinson's Disease Rating Scale part IV items 32 and 39. RESULTS: Overall, 375 patients were enrolled by 75 movement disorder centers in 18 countries and 258 patients completed the registry. At 24 months LCIG treatment led to significant reductions from baseline in "Off" time (hours/day) (mean ± SD = -4.1 ± 3.5, P < 0.001), "On" time with dyskinesia (hours/day) (-1.1 ± 4.8, P = 0.006), Non-Motor Symptom Scale total (-16.7 ± 43.2, P < 0.001) and individual domains scores, and Parkinson's Disease Questionnaire-8 item total score (-7.1 ± 21.0, P < 0.001). Adverse events deemed to have a possible/probable causal relationship to treatment drug/device were reported in 194 (54%) patients; the most frequently reported were decreased weight (6.7%), device related infections (5.9%), device dislocations (4.8%), device issues (4.8%), and polyneuropathy (4.5%). CONCLUSIONS: LCIG treatment led to sustained improvements in motor fluctuations, non-motor symptoms particularly sleep/fatigue, mood/cognition and gastrointestinal domains, as well as quality of life in advanced PD patients over 24 months. Safety events were consistent with the established safety profile of LCIG.
- MeSH
- antiparkinsonika aplikace a dávkování škodlivé účinky MeSH
- fixní kombinace léků MeSH
- gastrointestinální intubace MeSH
- gely MeSH
- karbidopa aplikace a dávkování škodlivé účinky MeSH
- levodopa aplikace a dávkování škodlivé účinky MeSH
- lidé středního věku MeSH
- lidé MeSH
- Parkinsonova nemoc farmakoterapie MeSH
- registrace MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- pozorovací studie MeSH
- MeSH
- karbidopa aplikace a dávkování farmakologie terapeutické užití MeSH
- kombinovaná farmakoterapie MeSH
- levodopa aplikace a dávkování farmakologie terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- Parkinsonova nemoc * farmakoterapie MeSH
- senioři MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
