Burden of non-motor symptoms in Parkinson's disease patients predicts improvement in quality of life during treatment with levodopa-carbidopa intestinal gel.

BACKGROUND AND PURPOSE: GLORIA, a registry conducted with 375 advanced Parkinson's disease patients treated with levodopa-carbidopa intestinal gel (LCIG) for 24 months in routine clinical care, demonstrated significant reductions from baseline in 'off' time and 'on' time with dyskinesia and improvements in the Non-Motor Symptom Scale (NMSS) total and individual domain scores, and in Parkinson's Disease Questionnaire 8 item (PDQ-8) total score. METHODS: Associations between baseline NMSS burden (NMSB), the multi-domain NMSS total score and the PDQ-8 total score were investigated for 233 patients. Baseline NMSB was assigned to five numerical categories defined by the NMSS total cutoff scores (0-20, 21-40, 41-60, 61-80 and >80). Pearson and Spearman correlations were calculated at month 24. RESULTS: The response of LCIG was assessed using validated criteria after 24 months. The proportion of patients decreasing ≥ 30 NMSS score points was 47% in the most affected NMSB category (NMSS total score > 80). A positive association was noted between baseline NMSB and NMSS total score (0.57, P < 0.0001), as well as between NMSS total score and PDQ-8 total score (0.46, P < 0.0001). Associations between improvements of the NMSS domain sleep/fatigue and PDQ-8 total score (0.32, P = 0.0001) as well as between the NMSS domain mood/cognition and PDQ-8 total score (0.37, P < 0.0001) were also shown. CONCLUSIONS: This analysis demonstrated positive associations between NMSS baseline burden and improvements of non-motor symptoms. Improvements of non-motor symptoms were associated with improved quality of life in advanced parkinsonian patients during a 2-year treatment with LCIG and reflect the long-term non-motor efficacy of this treatment.

Adherence to disease-modifying therapies in spanish patients with relapsing multiple sclerosis: two-year interim results of the global adherence project.

The post-marketing international Global Adherence Project investigated adherence to disease-modifying therapy for relapsing-remitting multiple sclerosis. We report adherence data from the first 2 years in the Spanish subset of patients (n = 254 at baseline). The overall adherence rate was 85.4%. Patients taking intramuscular (IM) interferon-ß (IFNß)-1a were significantly more adherent (96.4%) compared with patients taking subcutaneous (SC) IFNß-1a 22 µg (79.1%; p = 0.0064), SC IFNß-1a 44 µg (79.6%; p = 0.0064) and glatiramer acetate (82.7%; p = 0.0184). At year 1 (n = 142), the overall adherence rate was 86.6%. Patients on IM IFNß-1a were significantly more adherent than patients on SC IFNß-1a 22 µg (93.9 vs. 66.7%; p = 0.0251). At year 2 (n = 131), the overall adherence rate was 82% (87.5% for IM IFNß-1a, 80.0% for SC IFNß-1a 22 µg, 77.8% for SC IFNß-1a 44 µg, 85.2% for IFNß-1b, and 80.0% for glatiramer acetate). In conclusion, adherence remained high among all disease-modifying therapies over the first 2 years of the study and was significantly higher for IM IFNß-1a, at visit 1, compared with SC IFNß-1a.

Herramientas para mejorar la adherencia al tratamiento con inmunomoduladores en pacientes con esclerosis múltiple / Proposals to improve adherence to immunomodulatory therapies in patients with multiple sclerosis

Introducción: El objetivo de este trabajo fue evaluar los factores, identificados en el estudio global de adherencia (GAP), asociados con la adherencia a los fármacos inmunomoduladores (IMA) en pacientes con esclerosis múltiple (EM) para proponer medidas directas que mejoren la adherencia. Se propuso elaborar cuestionarios que permitiesen detectar, previamente y durante el seguimiento, a pacientes en riesgo de falta de adherencia.Métodos: Se celebraron dos reuniones con investigadores participantes en el estudio GAP en España. Se agruparon factores relacionados con la no adherencia asociados al tratamiento, paciente, enfermedad y profesionales de la salud. Se formaron 4 grupos de trabajo. Cada grupo trabajó de forma individual sobre un factor teniendo en cuenta el diagnóstico de la EM, manejo y aplicación de la medicación, seguimiento y retirada o cambio de tratamiento. Se acordó un borrador de propuestas y herramientas (cuestionarios).Resultados: Se debe proporcionar a los pacientes un resumen de las características de los tratamientos, de modo positivo y simple, así como tiempo para plantear dudas. La entrega de cuestionarios a los pacientes al inicio del tratamiento y durante el seguimiento para evaluar características individuales puede ayudar a conocer su grado de adherencia y actuar en consecuencia. Los pacientes deben ser educados en la identificación y el manejo de las reacciones adversas. Conclusiones: Se recomienda la educación terapéutica para favorecer la adherencia a los tratamientos e identificar a los pacientes no adherentes. Proponemos 2 cuestionarios, de inicio y de seguimiento, para poder estratificar a los pacientes en función de su adherencia (AU)

Introduction: The objective of this work was to assess the factors identified in the Global Adherence Project (GAP) in disease-modifying therapy (DMT) in patients with multiple sclerosis (MS) and to propose measures directed at improving adherence. It was proposed to prepare questionnaires to detect patients at risk of non-adherence before and during the follow-up. Methods: Two meetings were held by Spanish researchers involved in the GAP project. Factors associated with non-adherence were grouped in therapy-, patient-, disease- and health care professional-related factors. Four working groups were created. Each group studied one individual,factor, taking into account the stages of diagnosis, management and administering treatment, follow-up and discontinuation or change of treatment. A draft of proposals and tools (questionnaires) was agreed.Results: Patients should be provided with summaries of treatments, in a positive and simple way, and have time to discuss any doubts. Questionnaires should be given to patients at the start of treatment and during follow-up, so that individual characteristics can be assessed in order to monitor their adherence and act accordingly. Patients should be instructed in the management of the most common adverse reactions. Conclusion:Therapeutic education to improve adherence to treatments and identification of non-adherent patients is recommended. We propose 2 questionnaires, initial and follow up, to stratify patients depending on their adherence (AU)

[Proposals to improve adherence to immunomodulatory therapies in patients with multiple sclerosis]. / Herramientas para mejorar la adherencia al tratamiento con inmunomoduladores en pacientes con esclerosis múltiple.

INTRODUCTION: The objective of this work was to assess the factors identified in the Global Adherence Project (GAP) in disease-modifying therapy (DMT) in patients with multiple sclerosis (MS) and to propose measures directed at improving adherence. It was proposed to prepare questionnaires to detect patients at risk of non-adherence before and during the follow-up. METHODS: Two meetings were held by Spanish researchers involved in the GAP project. Factors associated with non-adherence were grouped in therapy-, patient-, disease- and health care professional-related factors. Four working groups were created. Each group studied one individual,factor, taking into account the stages of diagnosis, management and administering treatment, follow-up and discontinuation or change of treatment. A draft of proposals and tools (questionnaires) was agreed. RESULTS: Patients should be provided with summaries of treatments, in a positive and simple way, and have time to discuss any doubts. Questionnaires should be given to patients at the start of treatment and during follow-up, so that individual characteristics can be assessed in order to monitor their adherence and act accordingly. Patients should be instructed in the management of the most common adverse reactions. CONCLUSION: Therapeutic education to improve adherence to treatments and identification of non-adherent patients is recommended. We propose 2 questionnaires, initial and follow up, to stratify patients depending on their adherence.

[Global adherence project to disease-modifying therapies in patients with relapsing multiple sclerosis: 2-year interim results]. / Estudio global de adherencia a los tratamientos inmunomoduladores en pacientes con esclerosis múltiple remitente recidivante: resultados a 2 años.

BACKGROUND: In this article we report adherence data from the first 2 years in a subset of patients from the Global Adherence Project (GAP; n=2,648) in Spain. METHODS: A questionnaire assessing adherence to Disease-modifying therapies (DMTs), was distributed annually to patients and their treating neurologists. Non-adherence was defined as missing a DMT injection or changing a dose in the four weeks prior to completing the survey. Patients signed informed consent and Ethics Committees approved annual follow-ups, visit 1 (V1) and visit 2 (V2) in 15 out of 18 centres in Spain. RESULTS: A total of 254 patients were enrolled in Spain. Patients had a mean age of 37.9 years and 70.4% were female, and had been on their treatment for a median time of 28 months, and the overall adherence rate was 85.4%. Patients taking intramuscular interferon beta (IFNB)-1a (Avonex®) were significantly more adherent (94.6%) compared with patients taking subcutaneous (s.c.) IFNB-1a 22.g (Rebif®22) (79.1%; p=0.0064), s.c. IFNB-1a 44.g (Rebif®44) (79.6%; p=0.0064) and glatiramer acetate (GA) (82.7%; p=0.0184). At V1 (n=142), the overall adherence rate was 86.6% and patients on Avonex® were significantly more adherent than patients on Rebif®22 (93.9% versus 66.7%; p=0.0251). At V2 (n=131), the overall adherence rate was 82.4% (Avonex®, 87.5%; Rebif®22, 80%; Rebif®44, 77.8%; Betaferon®, 85.2%, and Copaxone®, 80%) without significant differences. CONCLUSIONS: Adherence remained high over the first 2 years of the study. It was highest with Avonex®, being significant on first assessment, after 40.5 months of therapy, on average compared with other DMTs and at year 1 compared with Rebif®22.

Estudio global de adherencia a los tratamientos inmunomoduladores en pacientes con esclerosis múltiple remitente recidivante: resultados a 2 años / Global adherence project to disease-modifying therapies in patients with relapsing multiple sclerosis: 2-year interim results

Introducción: En este artículo comunicamos resultados de adherencia a los 2 años en la subpoblación de pacientes del estudio Global de Adherencia GAP (n=2.648) en España. Métodos: Pacientes y neurólogos completaron cuestionarios anuales para evaluar la adherencia a los tratamientos inmunomoduladores (IMA). Se definió la falta de adherencia como la pérdida de una inyección o el cambio de dosis en las últimas 4 semanas previas a completar el cuestionario. Los pacientes firmaron el consentimiento informado. Estudio aprobado en 15 de 18 centros en los seguimientos anuales de la visita 1 (V1) y la visita 2 (V2) por los comités éticos. Resultados:Se incluyó a 254 pacientes en España; la media de edad fue 37,9 años y el 70,4% eran mujeres; la mediana de tiempo en tratamiento fue 28 meses y la tasa de adherencia conjunta, del 85,4%. Los pacientes en tratamiento con interferón beta (IFNB)-1a intramuscular (Avonex®) fueron significativamente más cumplidores (96,4%) que los pacientes tratados con IFNB-1a 22μg subcutáneo (s.c.) (Rebif®22) (79,1%; p=0,0064), IFNB-1a 44μg s.c. (Rebif®44) (79,6%; p=0,0064) y acetato de glatiramero (Copaxone®) (82,7%; p=0,0184). En V1 (n=142), la tasa de adherencia fue del 86,6%; los pacientes con Avonex® fueron significativamente más cumplidores que aquellos con Rebif®22 (el 93,9 frente al 66,7%; p=0,0251). En V2 (n=131), la tasa de adherencia fue del 82,4% (Avonex®, 87,5%; Rebif®22, 80%; Rebif®44, 77,8%; Betaferon®, 85,2%, y Copaxone®, 80%) sin diferencias significativas.Conclusiones: La adherencia permaneció alta los 2 años observados. Avonex® mostró mayor adherencia frente al resto; esta diferencia fue significativa en la visita basal, tras 40,5 meses de media en tratamiento y en V1 frente a Rebif®22 (AU)

Background: In this article we report adherence data from the first 2 years in a subset of patients from the Global Adherence Project (GAP; p=2,648) in Spain. Methods: A questionnaire assessing adherence to Disease-modifying therapies (DMTs), was distributed annually to patients and their treating neurologists. Non-adherence was defined as missing a DMT injection or changing a dose in the four weeks prior to completing the survey. Patients signed informed consent and Ethics Committees approved annual follow-ups, visit 1 (V1) and visit 2 (V2) in 15 out of 18 centres in Spain. Results: A total of 254 patients were enrolled in Spain. Patients had a mean age of 37.9 years and 70.4% were female, and had been on their treatment for a median time of 28 months, and the overall adherence rate was 85.4%. Patients taking intramuscular interferon beta (IFNB)-1a (Avonex®) were significantly more adherent (94.6%) compared with patients taking subcutaneous (s.c.) IFNB-1a 22μg (Rebif®22) (79.1%; p=0.0064), s.c. IFNB-1a 44μg (Rebif®44) (79.6%; p=0.0064) and glatiramer acetate (GA) (82.7%; p=0.0184). At V1 (n=142), the overall adherence rate was 86.6% and patients on Avonex® were significantly more adherent than patients on Rebif®22 (93.9% versus 66.7%; p=0.0251). At V2 (n=131), the overall adherence rate was 82.4% (Avonex®, 87.5%; Rebif®22, 80%; Rebif®44, 77.8%; Betaferon®, 85.2%, and Copaxone®, 80%) without significant differences.Conclusions: Adherence remained high over the first 2 years of the study. It was highest with Avonex®, being significant on first assessment, after 40.5 months of therapy, on average compared with other DMTs and at year 1 compared with Rebif®22 (AU)

Costs and quality of life of multiple sclerosis in Spain.

This cost-of-illness analysis is based on information from 1.848 patients in Spain and is part of a Europe-wide study on the costs of multiple sclerosis. The objective was to analyze the costs and quality of life (QOL) related to the level of disease severity and progression. Patients were identified by the Asociación Española de Esclerosis Múltiple (AEDEM) and participated in the survey by answering a mail questionnaire (response rate 31.8%). In addition to details on the disease (type of disease, relapses, level of functional disability), the questionnaire asked for information on all resource consumption, medical, non-medical, work absence and informal care, as well as utility (QOL). The mean age of the cohort was 45 years, and only 5.5% of patients were 65 years of age or more. Approximately 36% of patients had mild disease (Expanded Disability Status Scale [EDSS] score of 0-3), 44.8% had moderate disease (EDSS score of 4-6.5) and 17.7% had severe disease (EDSS score > or =7). The mean EDSS score in the sample was 4.5 (median 5.0), with a utility of 0.554. Costs and utility are highly correlated with disease severity. Workforce participation decreases from around 70% in early disease to less than 5% in the very late stages. Hospitalization is very infrequent in early disease, representing less than euro 1.300 per patient per year for patients at EDSS scores <6, but increases steeply for patients at scores > or =7. Ambulatory care increases fivefold between early and late disease, while investments and services increase from basically no cost to just over euro 6.000 at EDSS scores > or =7. Productivity losses increase more than eightfold, and informal care increases from euro 593 at EDSS scores of 0-1 to nearly euro 34.228 at scores of 8-9. Hence, total mean costs per patient are driven by the distribution of the severity levels in the sample, increasing from euro 10.425 at EDSS scores of 0-1 to euro 45.264 at a score of 7, and euro 65.693 at scores of 8-9. The same is true for utility, which decreases from 0.865 to 0.084 as patients progress from the mildest to the most severe disability levels. However, the utility loss compared to the age- and gender-matched general population is high at all levels of the disease ( approximately 0.25 in patients below 30 years of age with an EDSS score of 2-3, and approximately 0.4 in patients over 60 years of age and a score of > or =6), leading to an estimated annual loss of 0.276 quality-adjusted life-year per patient. Relapses for patients with an EDSS score below 5 are associated with a cost of approximately euro 2.750 and a utility loss of 0.1 during the quarter in which they occur.

Interferon beta-1b inhibits reactive oxygen species production in peripheral blood monocytes of patients with relapsing-remitting multiple sclerosis.

We studied the rate of reactive oxygen species (ROS) production by monocytes 'ex vivo' in a cohort of healthy individuals, in a group of MS patients undergoing treatment with interferon beta-1b and another group of MS patients who refused treatment with interferon beta-1b. The rate of ROS production in healthy individuals was slightly lower than in non-treated MS patients. The lower rate of ROS production was obtained in monocytes of MS patients treated with interferon beta-1b. These results indicate that the treatment of relapsing-remitting MS patients with interferon beta-1b rendered the NADPH oxidase of the monocytes less sensitive to trigger reactive oxygen species (ROS).