ABSTRACT
Opicapone is a catechol-O-methyl-transferase (iCOMT) inhibitor authorized in Europe in 2016 and indicated as adjunctive therapy to preparations of levodopa/ DOPA decarboxylase inhibitors in adult patients with Parkinson's disease and end-of-dose motor fluctuations who cannot be stabilised on those combinations. The efficacy of opicapone in these patients has been demonstrated in two pivotal randomized clinical trials, BIPARK I and BIPARK II, in which it has demonstrated its superiority versus placebo and non-inferiority versus entacapone. Although they constitute the gold standard for the evaluation of interventions, randomized clinical trials present limitations of external validity due to the use of strict eligibility criteria. Therefore, it is considered necessary to have a more comprehensive evaluation of the efficacy of the drug, complementing the information obtained from randomized clinical trials with that of "real world or real clinical practice" studies. The objective of this review has been to collect and put into perspective the information available on opicapone coming from real clinical practice studies in Spain. The data from Spain with opicapone in 18 series with more than 1,000 patients in total, confirm the safety and efficacy previously reported with this iCOMT. Furthermore, they show that opicapone is especially useful in patients with a less advanced stage of the disease and mild motor fluctuations, which would suggest that the earlier its introduction in the therapeutic scheme for the management of motor fluctuations, the better is the benefit-risk ratio for the drug.
TITLE: Opicapona para el tratamiento de la enfermedad de Parkinson: datos de vida real en España.Resumen. La opicapona es un inhibidor de la catecol-O-metiltransferasa (iCOMT) autorizado en Europa en 2016 como terapia adyuvante a las preparaciones de levodopa/inhibidores de la dopa descarboxilasa en pacientes adultos con enfermedad de Parkinson y fluctuaciones motoras de final de dosis que no puedan ser estabilizados con esas combinaciones. La eficacia de la opicapona en estos pacientes ha sido demostrada en dos ensayos clínicos pivotales, BIPARK I y BIPARK II, en los que se ha demostrado la superioridad frente al placebo y la no inferioridad frente a la entacapona. A pesar de que constituyen el estándar para la evaluación de intervenciones, los ensayos clínicos aleatorizados presentan limitaciones de validez externa debidas a la utilización de criterios estrictos de elegibilidad. Por tanto, se considera necesario disponer de una evaluación más amplia de la eficacia general del fármaco, complementando la información de los ensayos clínicos aleatorizados con estudios de 'vida real o práctica clínica real'. El objetivo de esta revisión ha sido recopilar y poner en perspectiva la información disponible sobre los resultados de la opicapona en estudios de práctica clínica real en España. Los datos acumulados en España con opicapona en 18 series con más de 1.000 pacientes confirman la seguridad y la eficacia de este iCOMT comunicadas previamente. Además, muestran que la opicapona es especialmente útil en pacientes en un estadio de la enfermedad menos avanzado y fluctuaciones motores leves, lo que sugeriría una mejor relación beneficio-riesgo cuanto más temprana sea su introducción en el esquema terapéutico para el tratamiento de las fluctuaciones motoras.
Subject(s)
Antiparkinson Agents/therapeutic use , Catechol O-Methyltransferase Inhibitors/therapeutic use , Oxadiazoles/therapeutic use , Parkinson Disease/drug therapy , Antiparkinson Agents/administration & dosage , Antiparkinson Agents/adverse effects , Combined Modality Therapy , Deep Brain Stimulation , Drug Therapy, Combination , Humans , Levodopa/administration & dosage , Levodopa/therapeutic use , Oxadiazoles/administration & dosage , Oxadiazoles/adverse effects , Parkinson Disease/therapy , Quality of Life , Randomized Controlled Trials as Topic , Retrospective Studies , Risk Assessment , Spain , Treatment OutcomeABSTRACT
BACKGROUND AND PURPOSE: The objective of this study was to analyze the relationship between motor complications and non-motor symptom (NMS) burden in a population of patients with Parkinson's disease (PD) and also in a subgroup of patients with early PD. METHODS: Patients with PD from the COPPADIS cohort were included in this cross-sectional study. NMS burden was defined according to the Non-Motor Symptoms Scale (NMSS) total score. Unified Parkinson's Disease Rating Scale (UPDRS) part IV was used to establish motor complication types and their severity. Patients with ≤5 years of symptoms from onset were included as patients with early PD. RESULTS: Of 690 patients with PD (62.6 ± 8.9 years old, 60.1% males), 33.9% and 18.1% presented motor fluctuations and dyskinesia, respectively. The NMS total score was higher in patients with motor fluctuations (59.2 ± 43.1 vs. 38.3 ± 33.1; P < 0.0001) and dyskinesia (63.5 ± 40.7 vs. 41.4 ± 36.3; P < 0.0001). In a multiple linear regression model and after adjustment for age, sex, disease duration, Hoehn & Yahr stage, UPDRS-III score and levodopa equivalent daily dose, UPDRS-IV score was significantly related to a higher NMSS total score (ß = 0.27; 95% confidence intervals, 2.81-5.61; P < 0.0001), as it was in a logistic regression model on dichotomous NMSS total score (≤40, mild or moderate vs. >40, severe or very severe) (odds ratio, 1.31; 95% confidence intervals, 1.17-1.47; P < 0.0001). In the subgroup of patients with early PD (n = 396; mean disease duration 2.7 ± 1.5 years), motor fluctuations were frequent (18.1%) and similar results were obtained. CONCLUSIONS: Motor complications were frequent and were associated with a greater NMS burden in patients with PD even during the first 5 years of disease duration.
Subject(s)
Parkinson Disease , Aged , Cross-Sectional Studies , Female , Humans , Levodopa/therapeutic use , Male , Middle Aged , Parkinson Disease/complications , Parkinson Disease/epidemiology , Severity of Illness IndexABSTRACT
Introducción: Los trastornos del control de los impulsos (TCI) son una complicación que puede aparecer en los pacientes con enfermedad de Parkinson (EP). Su presencia se ha relacionado con diversos factores y confiere tal gravedad clínica que obliga a realizar un abordaje específico y multidisciplinar. El objetivo de este estudio fue evaluar la frecuencia y los factores tanto clínicos como psicopatológicos asociados a su aparición. Métodos: Estudio transversal, descriptivo y analítico con una muestra de pacientes con EP a quienes se evaluó la presencia de algún TCI. Se administraron escalas clínicas para valorar la gravedad de la enfermedad, los rasgos de personalidad y diferentes síntomas psicopatológicos presentes en el momento de la valoración. Resultados: La muestra fue de 115 pacientes, de los cuales un 23,48% (n = 27) presentaba algún TCI, siendo los más frecuentes la hipersexualidad en el 12,2% (n = 14) y la ingesta compulsiva en el 10,1% (n = 12). De los diferentes factores clínicos y psicopatológicos analizados, se asociaron con la presencia de TCI el tratamiento con agonistas dopaminérgicos (OR: 13,39), la edad de inicio más precoz de la enfermedad (OR: 0,92), una puntuación mayor en la escala UPDRS-I (OR: 1,93), la ansiedad como rasgo (OR: 1,05) y la impulsividad no planificada (OR: 1,13). Conclusiones: Los TCI son frecuentes en la EP. El tratamiento con agonistas dopaminérgicos es el factor de riesgo más importante. Niveles elevados de impulsividad y ansiedad en el momento de la valoración, así como una edad de inicio precoz, incrementan el riesgo. Sin embargo, los rasgos de personalidad previos no confieren un mayor riesgo
Introduction: Impulse control disorders (ICD) constitute a complication that may arise during the course of Parkinson's disease (PD). Several factors have been linked to the development of these disorders, and their associated severe functional impairment requires specific and multidisciplinary management. The objective of this study was to evaluate the frequency of ICDs and the clinical and psychopathological factors associated with the appearance of these disorders. Methods: Cross-sectional, descriptive, and analytical study of a sample of 115 PD patients evaluated to determine the presence of an ICD. Clinical scales were administered to assess disease severity, personality traits, and presence of psychiatric symptoms at the time of evaluation. Results: Of the 115 patients with PD, 27 (23.48%) displayed some form of ICD; hypersexuality, exhibited by 14 (12.2%), and binge eating, present in 12 (10.1%), were the most common types. Clinical factors associated with ICD were treatment with dopamine agonists (OR: 13.39), earlier age at disease onset (OR: 0.92), and higher score on the UPDRS-I subscale; psychopathological factors with a significant association were trait anxiety (OR: 1.05) and impulsivity (OR: 1.13). Conclusions: ICDs are frequent in PD, and treatment with dopamine agonists is the most important risk factor for these disorders. High impulsivity and anxiety levels at time of evaluation, and younger age at disease onset, were also linked to increased risk. However, presence of these personality traits prior to evaluation did not increase risk of ICD
Subject(s)
Humans , Male , Female , Dopamine Agonists/administration & dosage , Dopamine Agonists/adverse effects , Dopamine Agonists/therapeutic use , Dopamine Agents/administration & dosage , Dopamine Agents/adverse effects , Dopamine Agents/therapeutic use , Parkinson Disease/complications , Parkinson Disease/epidemiology , Parkinson Disease/therapy , Disruptive, Impulse Control, and Conduct Disorders/diagnosis , Disruptive, Impulse Control, and Conduct Disorders/psychology , Disruptive, Impulse Control, and Conduct Disorders/therapy , Personality/physiology , Psychopathology/instrumentation , Psychopathology/methods , Epidemiology, Descriptive , Cross-Sectional Studies , Psychotic Disorders/psychology , Psychotic Disorders/therapy , Compulsive Behavior/psychology , Compulsive Behavior/therapy , SpainABSTRACT
INTRODUCTION: Impulse control disorders (ICD) constitute a complication that may arise during the course of Parkinson's disease (PD). Several factors have been linked to the development of these disorders, and their associated severe functional impairment requires specific and multidisciplinary management. The objective of this study was to evaluate the frequency of ICDs and the clinical and psychopathological factors associated with the appearance of these disorders. METHODS: Cross-sectional, descriptive, and analytical study of a sample of 115 PD patients evaluated to determine the presence of an ICD. Clinical scales were administered to assess disease severity, personality traits, and presence of psychiatric symptoms at the time of evaluation. RESULTS: Of the 115 patients with PD, 27 (23.48%) displayed some form of ICD; hypersexuality, exhibited by 14 (12.2%), and binge eating, present in 12 (10.1%), were the most common types. Clinical factors associated with ICD were treatment with dopamine agonists (OR: 13.39), earlier age at disease onset (OR: 0.92), and higher score on the UPDRS-I subscale; psychopathological factors with a significant association were trait anxiety (OR: 1.05) and impulsivity (OR: 1.13). CONCLUSIONS: ICDs are frequent in PD, and treatment with dopamine agonists is the most important risk factor for these disorders. High impulsivity and anxiety levels at time of evaluation, and younger age at disease onset, were also linked to increased risk. However, presence of these personality traits prior to evaluation did not increase risk of ICD.
