Acceso a medicamentos huérfanos para el tratamiento de la atrofia muscular espinal en España / Access to orphan drugs for the treatment of spinal muscular atrophy in Spain

Introducción: La atrofia muscular espinal (AME) es una enfermedad rara cuyo diagnóstico y tratamiento es complejo. En España hay dos medicamentos huérfanos financiados por el Sistema Nacional de Salud, nusinersén y onasemnogén abeparvovec, y un tercero, risdiplam, pendiente. El objetivo fue analizar el acceso a los fármacos modificadores de la AME y detectar posibles causas de inequidad. Materiales y método: Estudio descriptivo realizado en dos fases: revisión bibliográfica y entrevistas semiestructuradas a expertos clínicos en AME de las comunidades autónomas (CC. AA.) de Andalucía, Castilla-La Mancha, Cataluña y Murcia. Resultados: El número de centros, servicios o unidades de referencia, la disponibilidad de planes autonómicos para enfermedades raras y los programas piloto de cribado neonatal pueden modular el acceso a los nuevos tratamientos farmacológicos. El número de nuevos pacientes diagnosticados al año se estimó entre uno y seis en cada una de las CC. AA. estudiadas. Dos de las cuatro CC. AA. estaban participando en ensayos clínicos. El tiempo desde la prescripción a la administración de nusinersén estaba entre siete y 60 días. Sólo Cataluña comunicó experiencia con onasemnogén abeparvovec a 30 de junio de 2022. Dos CC. AA. de las cuatro estudiadas disponen de plan autonómico para enfermedades raras; no obstante, se identificó como relevante para el tratamiento de la AME sólo en una de ellas. Conclusiones: No se identificaron diferencias importantes en el acceso al nusinersén en las CC. AA. estudiadas. El diagnóstico de la AME requiere personal clínico experto y centros especializados para iniciar precozmente los tratamientos modificadores de la enfermedad.(AU)

Introduction: Spinal muscular atrophy (SMA) is a rare disease whose diagnosis and treatment are complex. In Spain, there are two orphan medicines that are currently financed by the state, nusinersen and onasemnogene abeparvovec and, a third in process, risdiplam. The objective was to detect possible causes of inequity in the diagnosis and treatment of SMA in Spain. Materials and method: Descriptive study realized in two phases: a first phase of bibliographic revision and a second phase of semi-structured interviews with clinical experts in SMA in Andalusia, Castilla-La Mancha, Catalonia and Murcia. Results: The number of centers, services or units of reference, the availability of regional autonomous plans for rare diseases and pilot programs of neonatal screenings can regulate access to treatments. The number of new patients diagnosed per year is estimated between one and six in the four autonomous communities (ACs) of Spain studied. Differences were not found in logistical resources. Two of the four ACs studied have regional autonomous plans for rare diseases, however, their utility has only had relevance in one of two of the ACs. Conclusions: Important differences in access to nusinersen were not identified in the studied ACs The diagnosis of SMA requires clinical specialized experts and specialized centers for early intervention of disease-modifying therapies.(AU)

[Access to orphan drugs for the treatment of spinal muscular atrophy in Spain]. / Acceso a medicamentos huérfanos para el tratamiento de la atrofia muscular espinal en España.

INTRODUCTION: Spinal muscular atrophy (SMA) is a rare disease whose diagnosis and treatment are complex. In Spain, there are two orphan medicines that are currently financed by the state, nusinersen and onasemnogene abeparvovec and, a third in process, risdiplam. The objective was to detect possible causes of inequity in the diagnosis and treatment of SMA in Spain. MATERIALS AND METHOD: Descriptive study realized in two phases: a first phase of bibliographic revision and a second phase of semi-structured interviews with clinical experts in SMA in Andalusia, Castilla-La Mancha, Catalonia and Murcia. RESULTS: The number of centers, services or units of reference, the availability of regional autonomous plans for rare diseases and pilot programs of neonatal screenings can regulate access to treatments. The number of new patients diagnosed per year is estimated between one and six in the four autonomous communities (ACs) of Spain studied. Differences were not found in logistical resources. Two of the four ACs studied have regional autonomous plans for rare diseases, however, their utility has only had relevance in one of two of the ACs. CONCLUSIONS: Important differences in access to nusinersen were not identified in the studied ACs The diagnosis of SMA requires clinical specialized experts and specialized centers for early intervention of disease-modifying therapies.

TITLE: Acceso a medicamentos huérfanos para el tratamiento de la atrofia muscular espinal en España.Introducción. La atrofia muscular espinal (AME) es una enfermedad rara cuyo diagnóstico y tratamiento es complejo. En España hay dos medicamentos huérfanos financiados por el Sistema Nacional de Salud, nusinersén y onasemnogén abeparvovec, y un tercero, risdiplam, pendiente. El objetivo fue analizar el acceso a los fármacos modificadores de la AME y detectar posibles causas de inequidad. Materiales y método. Estudio descriptivo realizado en dos fases: revisión bibliográfica y entrevistas semiestructuradas a expertos clínicos en AME de las comunidades autónomas (CC. AA.) de Andalucía, Castilla-La Mancha, Cataluña y Murcia. Resultados. El número de centros, servicios o unidades de referencia, la disponibilidad de planes autonómicos para enfermedades raras y los programas piloto de cribado neonatal pueden modular el acceso a los nuevos tratamientos farmacológicos. El número de nuevos pacientes diagnosticados al año se estimó entre uno y seis en cada una de las CC. AA. estudiadas. Dos de las cuatro CC. AA. estaban participando en ensayos clínicos. El tiempo desde la prescripción a la administración de nusinersén estaba entre siete y 60 días. Sólo Cataluña comunicó experiencia con onasemnogén abeparvovec a 30 de junio de 2022. Dos CC. AA. de las cuatro estudiadas disponen de plan autonómico para enfermedades raras; no obstante, se identificó como relevante para el tratamiento de la AME sólo en una de ellas. Conclusiones. No se identificaron diferencias importantes en el acceso al nusinersén en las CC. AA. estudiadas. El diagnóstico de la AME requiere personal clínico experto y centros especializados para iniciar precozmente los tratamientos modificadores de la enfermedad.

Clinicopathologic features and outcomes of neuro-Behçet disease in Spain: a study of 20 patients.

BACKGROUND: To describe the clinical characteristics and evolution of a series of adult patients hospitalized for neuro-Behçet disease (NBD). METHODS: Consecutive patients admitted for NBD in a teaching hospital were retrospectively selected. Disability at discharge and during follow-up was graded with the modified Rankin Scale, and outcome classified as good or poor (grades 3-6). RESULTS: Twenty patients were included (M/F, 13/7). Mean age at NBD diagnosis was 36.3 years. Nineteen patients had other manifestations of Behçet disease (BD) before NBD developed, but only 7 met the complete diagnostic criteria for BD. Fever, headache, motor weakness, and cranial nerve palsy were each present in approximately 60% of patients. There was a low prevalence of behavioral changes (5%), seizures (5%), and sphincter incontinence (0%), and a relatively high prevalence of meningism (25%). Non-neurologic manifestations of BD were concurrently detected in 15 patients (75%). 80% had parenchymal involvement. Brain biopsies during 5 attacks showed perivascular lymphocytic infiltration with reactive astrocytosis, but no frank vasculitis. During a mean follow-up of 6.3 years per patient, 12 had at least one relapse. In total, there were 22 relapses; all but two were in the same location and were symptomatically similar in each patient. At the end of follow-up, 7 patients (35%) had a poor outcome, including 4 who died. CONCLUSION: Recording of previous manifestations of BD and a physical examination to detect concomitant systemic manifestations of BD may help establish an early diagnosis of NBD. Relapses frequently occurred in the same location. No frank vasculitis was present in brain biopsies.

Neuro-Behçet y neurotoxicidad por ciclosporina / Neuro-Behçet and neurotoxicity due to cyclosporine

No disponible

An approach to estimating the intangible costs of multiple sclerosis according to disability in Catalonia, Spain.

Multiple sclerosis (MS) is a chronic demyelinating disease, which represents a great economic burden to society. Cost-of-illness studies of MS tend to underestimate the intangible costs related to pain, anxiety and helplessness. The purpose of this study was to estimate the intangible costs of MS, and determine whether these costs increase as disability progresses. We studied 211 consecutive patients with MS who attended our MS unit. Patients mean age was 41.6 (SD: 10.7) years, 69% were female, and their mean Expanded Disability Status Scale (EDSS) score was 2.47 (SD: 2.05). Quality-of-life was measured with the EuroQoL visual analogue scale. Quality-adjusted life year (QALY) was calculated for each patient. Patients were grouped into five disability stages according to their EDSS, and QALY was compared between patients and a group of healthy controls matched by age and sex. A benchmark value was ascribed to each QALY lost, and the intangible costs per patient-year were calculated as Euros 0 (EDSS =0), Euros 1100 (EDSS =1-3), Euros 8250 (EDSS =3.5-5.5), Euros 9900 (EDSS =6-7) and Euros 11,000 (EDSS >7.5). Sensitivity analysis showed a similar progression of costs. We conclude that intangible costs are relevant in MS, especially when disability increases. Although the method to calculate the costs remains controversial, we consider that they should be included in cost analysis of MS.

[The costs of a multiple sclerosis relapse in Catalonia (Spain)]. / ¿Cuánto cuesta un brote de esclerosis múltiple en Cataluña?

INTRODUCTION: The objective of this study is to calculate direct, indirect and intangible costs of a relapse in multiple sclerosis (MS) in our cohort of patients. METHODS: Data from patient questionnaires, hospital charts, Catalan Public Healthcare System tariffs and Catalan Statistics Institute. We employed a cost-of-illness method. The human capital approach was used to estimate indirect costs, and quality-of-life measurements were used to estimate intangible costs. RESULTS: 148 MS patients monitored in our MS-Unit consecutively answered the questionnaire elaborated. We calculated 1,498.5-1,537.9 euros for direct costs (hospital admission and outpatient, respectively) and 1,530.6 euros for indirect costs. We estimated an average total cost of 3,048.8 euros per patient/relapse. We also calculated intangible costs, 539 euros per patient and relapse, which should be added to the previous figure. CONCLUSIONS: The total cost of a MS relapse in our population (3,048.8 euros) is lower than the cost reported in the literature. The economic impact of MS is due to its disabling progression rather than to relapses

¿Cuánto cuesta un brote de sclerosis multiple en Calauña? / The costs of a multiple sclerosis relapse in Catalonia (Spain)

Introducción. El objetivo de este trabajo es calcular los costes directos, indirectos e intangibles de un brote de esclerosis múltiple (EM) en nuestra cohorte de pacientes. Métodos. Partimos de datos obtenidos de cuestionarios del paciente, historias clínicas, tarifas del Servicio Catalán de Salud e Instituto de Estadística de Cataluña. Realizamos un estudio del coste de la enfermedad con el método del capital humano para estimar los costes indirectos y medidas de calidad de vida para estimar los gastos intangibles. Resultados. Ciento cuarenta y ocho pacientes afectos de EM, controlados en nuestra unidad, que contestaron, consecutivamente, al cuestionario elaborado. Los costes directos resultan 1.498,5-1.537,9 euros (hospitalizado y ambulatorio, respectivamente) y los indirectos 1.530,6 euros. El coste medio total estimado es de 3.048,8 euros por paciente y brote. Los gastos intangibles a añadir al coste total resultan 539 euros por paciente y brote. Conclusiones. El coste total de un brote de EM estimado en nuestra población (3.048,8 euros) es menor que lo publicado anteriormente. El gran impacto económico de la EM vendrá dado fundamentalmente por la progresión de la discapacidad más que por los brotes (AU)

Introduction: The objective of this study is to calculate direct, indirect and intangible costs of a relapse in multiple sclerosis (MS) in our cohort of patients. Methods: Data from patient questionnaires, hospital charts, Catalan Public Healthcare System tariffs and Catalan Statistics Institute. We employed a cost-of-illness method. The human capital approach was used to estimate indirect costs, and quality-of-life measurements were used to estimate intangible costs. Results: 148 MS patients monitored in our MS-Unit consecutively answered the questionnaire elaborated. We calculated 1,498.5-1,537.9 euros for direct costs (hospital admission and outpatient, respectively) and 1,530.6 euros for indirect costs. We estimated an average total cost of 3,048.8 euros per patient/relapse. We also calculated intangible costs, 539 euros per patient and relapse, which should be added to the previous figure. Conclusions: The total cost of a MS relapse in our population (3,048.8 euros) is lower than the cost reported in the literature. The economic impact of MS is due to its disabling progression rather than to relapses (AU)

Idiopathic acute transverse myelitis: a clinical study and prognostic markers in 45 cases.

OBJECTIVE: The Transverse Myelitis Consortium Working Group has proposed new diagnostic criteria for idiopathic acute transverse myelitis (ATM). We reviewed patients admitted to our center diagnosed with myelitis with two objectives: (i) to evaluate the usefulness of these criteria in distinguishing between myelitis as the first episode of multiple sclerosis (MS) and idiopathic ATM; and (ii) to analyse the clinical and laboratory variables that may be used as functional prognostic markers. METHODS: We selected patients who met the criteria. We recorded clinical epidemiological data, patients treated with methylprednisolone, maximal disability reached and disability at final follow-up. We also recorded cerebrospinal fluid (CSF) data and the number of levels affected in the spinal magnetic resonance imaging (MRI). RESULTS: Twenty-four patients fulfilled the criteria for definite ATM and 21 for possible ATM. Five patients converted to MS. Mean follow-up time was 3.5 years. There was an association between younger patients and female patients with conversion to MS. The highest Rankin score reached and increased CSF glucose levels were associated with a poor outcome. In multivariate analysis, only the admission Rankin score was associated with outcome. CONCLUSIONS: (i) About 10% of patients who met the criteria may convert to MS; and (ii) admission Rankin score was the only independent prognostic factor found.

Regression to the mean in multiple sclerosis.

In order to ensure sufficient disease activity, patients with relapsing remitting (RR) multiple sclerosis (MS) are often included in randomized placebo-controlled trials, only if they have a high baseline activity. These patients, whose evolution is unusual in the pre-study period, will tend to show a more usual behavior when followed up over a period of time. This phenomenon is known as regression to the mean. Regression to the mean should be taken into account in correctly interpreting long-term studies of cohorts treated without a placebo control group, which use the baseline period as control. The aim of this study was to evaluate the relevance of this phenomenon in a non-treated cohort of RRMS patients, selected with similar criteria to those used in randomized placebo-controlled clinical trials. Forty-four patients with definite RRMS, with two or more relapses in the previous two years, and a baseline EDSS < or = 5.5 were prospectively followed. The mean number of relapses spontaneously decreased from 1.72 (SD: 1.4) in the year prior to enrolment, to 1.0 (SD: 1.3) during the first year of follow-up (P < 0.05). Regression to the mean may explain as much as 40% of the reduction in the relapse rate from the baseline period to the period on-study.

Estudio de la demanda de electromiografía en un hospital general básico / A study of the demand for electromyography in a general hospital

No disponible

No disponible

Clinical benefits of interferon beta-1a in relapsing-remitting MS: a phase IV study.

OBJECTIVE: To evaluate the efficacy and safety of IFNbeta-1a (Avonex, Biogen, Inc., Cambridge, MA, USA) in patients with relapsing-remitting multiple sclerosis (MS). METHODS: In this multicenter, open-label, prospective clinical trial, 96 patients with relapsing-remitting MS received IFNbeta-1a 30 mcg intramuscularly once weekly for 2 years. Outcome variables included: change from baseline in mean number of exacerbations, proportion of exacerbation-free patients, and mean Expanded Disability Status Scale (EDSS) scores at Years 1 and 2. RESULTS: IFNbeta-1a significantly (P < 0.0001) reduced exacerbation rate at Years 1 and 2 of treatment. The percentage of exacerbation-free patients was 53% during Year 1 and 33% during Year 2. Mean EDSS scores were 2.96 +/- 1.26 at baseline, 2.89 +/- 1.42 at Year 1, and 3.00 +/- 1.62 at Year 2 (P = 0.116). EDSS scores improved in 35.4%, remained stable in 28.1%, and worsened in 36.5% of patients. IFNbeta-1a treatment was well tolerated. CONCLUSION: This study confirms and extends the beneficial clinical profile for IFNbeta-1a in relapsing MS.

[Impairment, disability and handicap scales in multiple sclerosis]. / Escalas de deterioro, discapacidad y minusvalía en la esclerosis múltiple.

INTRODUCTION AND METHOD: In recent years the need to create scales for measuring the dysfunction or impairment suffered by patients with multiple sclerosis has increased. The aim of the scales that measure neurological impairment is two fold: to homogenise the data from different series so that studies into the prognosis and natural history of the disease can be compared, and to measure the changes in the progress of the disease when a therapy has been established. Over the past few years a large number of scales have appeared that attempt to redress the shortcomings of the EDSS (Expanded Disability Status Scale). The latest of these, the MSF Composite, manages to overcome the statistical problems of the EDSS and enables significant differences between two groups to be detected when studying the effect of a treatment. CONCLUSIONS: In the coming years we will possibly witness a joint use of several of the scales described, and both the EDSS and the Composite will be employed together in the evaluation of patients in therapeutic protocols, perhaps together with a quality of life scale.

Escalas de deterioro, discapacidad y minusvalía en la esclerosis múltiple / Impairment, disability and handicap scales in multiple sclerosis

Introducción y desarrollo. Durante los últimos años ha aumentado la necesidad de crear escalas de medición de la disfunción o deterioro que sufren los pacientes con esclerosis múltiple. El objetivo de las escalas que miden el deterioro neurológico es doble: homogeneizar los datos de las diferentes series para que los estudios pronósticos y de historia natural de la enfermedad sean comparables, y medir los cambios en la evolución de la enfermedad cuando se instaura una terapia. Han aparecido en los últimos años un gran número de escalas que intentan solventar los déficit de la EDSS ( Expanded Disability Status Scale). La última de todas, el MSF Composite, consigue evitar los problemas estadísticos de la EDSS y permite encontrar diferencias significativas entre dos grupos al estudiar el efecto de un tratamiento. Conclusiones. Posiblemente en los años venideros asistamos a una utilización conjunta de varias de las escalas que se detallan, y tanto la EDSS como el Composite se empleen de forma conjunta en la valoración de enfermos en protocolos terapéuticos, quizá junto con alguna escala de calidad de vida (AU)

14-3-3 protein in the CSF as prognostic marker in early multiple sclerosis.

Axonal damage probably occurs early in the evolution of MS. Five of 38 (13%) patients had a positive assay for the neuronal 14-3-3 protein in the CSF obtained at the first clinically isolated syndrome suggestive of MS. A positive 14-3-3 assay was the only independent predictor for a shorter time to conversion to clinical definite MS (risk ratio 4.1; 95% CI 1.1 to 15) and to reach an Expanded Disability Status Scale (EDSS) > or =2 at the end of follow-up (odds ratio 14.8; 95% CI 2.86 to 76.8). The detection of the 14-3-3 protein in the CSF at the first neurologic event suggestive of MS may be a useful predictor of short-term evolution.

[Axonal damage in multiple sclerosis]. / Daño axonal en la esclerosis múltiple.

The presence of axonal lesions in plaques of demyelination in patients with multiple sclerosis (MS) has been known for many years. Traditionally it was believed that axonal loss occurred in chronic lesions. However, demonstration of pathological degeneration in active plaques, use of new resonance techniques such as spectroscopy or the transfer of magnetization, showing axonal damage in white matter of apparently normal aspect, and the presence of axonal neurofilaments in the cerebrospinal fluid during the episode has made it necessary to reconsider the contribution made by axonal damage to the pathogenesis of MS. Besides, recent studies have shown that a factor present in the cerebrospinal fluid of patients with MS may contribute to the induction of neuronal apoptosis. These facts, apart from their pathogenic implications and consequent clinical repercussions, will affect investigation of alternative treatments for this disorder, and by means of clinico-immunoradiological correlation will help to define the prognosis of the course of the disorder in these patients.