Efecto del acetato de glatirámero sobre la espasticidad en esclerosis múltiple recurrente remitente

La esclerosis múltiple (EM) es una enfermedad desmielinizante, degenerativa y con patogenia inmuno mediada que afecta al Sistema Nervioso Central (SNC). En su manejo, resulta esencial instaurar precozmente uno de los denominados “tratamientos modificadores del curso de la enfermedad” (MCE) para evitar la aparición de brotes y progresión de la discapacidad, responsables de graves limitaciones funcionales. Por otra parte, la espasticidad es uno de los síntomas más invalidantes que se producen durante la evolución de la enfermedad y que de forma más negativa influye en la calidad de vida del paciente. Su identificación y manejo precoz resulta fundamental para evitar complicaciones irreversibles. El tratamiento sintomático de la espasticidad con fármacos antiespásticos es en muchas ocasiones ineficaz y mal tolerado por la aparición frecuentes efectos adversos concomitantes. Dos de los fármacos más comúnmente empleados como MCE son el interferón beta (IFNB) y el acetato de glatirámero (AG) y es habitual observar una permuta en su utilización por diferentes circunstancias. Se tienen algunas evidencias de la influencia negativa del tratamiento con IFNB sobre la espasticidad, pero no existen estudios acerca de la influencia que el tratamiento con AG produce sobre este síntoma. El trabajo desarrollado en esta tesis ha permitido establecer qué efecto produce el tratamiento con AG sobre la espasticidad y la calidad de vida en pacientes con EM recurrente remitente (EMRR) y espasticidad que han sido tratados previamente con IFNB, así como la influencia que ejerce la medicación sintomática espasmolítica. Además se ha realizado una aproximación acerca de la repercusión económica y laboral que tiene la acción de AG sobre la espasticidad. Este trabajo también ha permitido concluir acerca del efecto de AG sobre la espasticidad en pacientes con EMRR y espasticidad que previamente no han sido tratados con ningún fármaco MCE. El objetivo primario de esta tesis es estudiar el efecto de AG sobre la espasticidad en pacientes con EMRR y espasticidad que han sido tratados previamente con IFNB y los objetivos secundarios son: 1. Estudiar el efecto de AG sobre la espasticidad en pacientes con EMRR y espasticidad que previamente no han sido tratados con ningún fármaco MCE. 2. Conocer la influencia de la medicación sintomática antiespástica sobre la espasticidad en pacientes con EMRR que han cambiado el tratamiento con IFNB por AG. 3. Estudiar si existe variación en la calidad de vida de los pacientes con EMRR y espasticidad que cambian el tratamiento con IFNB por AG. 4. Describir la repercusión económica y laboral al cambiar el tratamiento con IFNB por AG en pacientes con EMRR y espasticidad. Las conclusiones de esta tesis son: 1. El tratamiento con AG, en pacientes con EMRR y espasticidad que previamente han estado en tratamiento con IFNB, produce una mejoría del grado de espasticidad, que se inicia de forma precoz. 2. El tratamiento con AG, en pacientes con EMRR y espasticidad que previamente no han sido tratados con ningún fármaco MCE, no produce un aumento de la espasticidad. 3. La influencia de la medicación sintomática antiespástica sobre la espasticidad, en pacientes con EM y espasticidad que han cambiado el tratamiento con IFNB por AG, es escasa o nula. 4. El tratamiento con AG, en pacientes con EMRR y espasticidad que previamente han estado en tratamiento con IFNB, produce una mejoría de la calidad de vida. 5. El tratamiento con AG, en pacientes con EMRR y espasticidad previamente tratados con IFNB, produce un ahorro en los costes de la enfermedad y una reducción en la pérdida de días laborables.Medicin

Effectiveness of Fingolimod versus Natalizumab as Second-Line Therapy for Relapsing-Remitting Multiple Sclerosis in Spain: Second-Line GATE Study

Background: There is a lack of head-to-head studies comparing the efficacy of fingolimod (FIN) and natalizumab (NTZ) as second-line therapy for relapsing-remitting multiple sclerosis (RRMS). Methods: Multicenter, observational study, in which, information of 388 patients randomly selected and treated with FIN or NTZ in routine clinical practice was retrospectively collected with the main objective of comparing the annualized relapse rate (ARR) over the first year, after FIN or NTZ treatment initiation. Results: Mean ARR during the first year of treatment was 0.28 in FIN group and 0.12 in NTZ group (p = 0.0064); nevertheless, the difference between groups lost statistical significance when the propensity score analysis was performed. Time to disability -progression was similar in both treatment groups (12.3 +/- 6.7 months in FIN, and 12.8 +/- 0.1 months in NTZ; p = 0.4654). Treatment persistence after the first year of treatment was higher in patients treated with FIN (95%) than in those treated with NTZ (84%; p = 0.0014). Conclusions: After 12 months of treatment, both FIN and NTZ reduced the ARR, but ARR percent reduction was significantly higher with NTZ. Treatment persistence was higher in patients receiving FIN

CLIPPERS syndrome with atypical distribution of lesions in magnetic resonance imaging of the brain

Introducción. El síndrome CLIPPERS (chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids) es un proceso inflamatorio del sistema nervioso central cuyo rasgo distintivo son las lesiones puntiformes en el troncoencéfalo captantes en los estudios de resonancia magnética. Clínicamente, cursa con disartria, ataxia y diplopía, y suele responder a corticoides. Anatomopatológicamente, aparecen infiltrados de linfocitos T en los espacios perivasculares troncoencefálicos. Caso clínico. Mujer de 40 años con cuadro de instauración subaguda de diplopía binocular, ataxia y disartria. En la resonancia magnética cerebral presentó lesiones puntiformes hipertintensas en secuencia T2 en el tronco, cerebelo, diencéfalo y áreas córtico-subcorticales bihemisféricas, que realzaron con contraste. Se realizó un estudio etiológico para descartar un origen infeccioso, neoplásico o inflamatorio subyacente, que resultó negativo. La paciente recibió tratamiento en dos ocasiones con metilprednisolona, con descenso progresivo de la dosis, con buena respuesta. Conclusiones. La diplopía y la ataxia, como en nuestro caso, están presentes prácticamente siempre. Los hallazgos en la RM consisten en lesiones captantes puntiformes localizadas en la protuberancia con extensión hacia el cerebelo, ganglios basales y cuerpo calloso, con gradiente de captación menor conforme se alejan rostralmente hacia la corteza, y caudalmente hacia la médula. En el caso de nuestra paciente, este gradiente no se respeta, encontrándose una densidad similar de las lesiones a nivel supratentorial. El diagnóstico diferencial es amplio y justifica un estudio diagnóstico extenso, y en casos seleccionados la biopsia cerebral. El curso de la enfermedad es remitente-recurrente, y el pronóstico mejora cuanto más precoz y prolongado es el tiempo de corticoterapiaIntroduction. CLIPPERS syndrome (chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids) is an inflammatory process of the central nervous system whose distinguishing features are the enhancing punctiform lesions in the brainstem that appear in the magnetic resonance images. Clinically, it is accompanied by dysarthria, ataxia and diplopia, and usually responds to treatment with corticoids. Pathologically, T lymphocytes appear infiltrated in the perivascular spaces of the brainstem. Case report. We report the case of a 40-year-old woman with an initial subacute clinical picture of binocular diplopia, ataxia and dysarthria. The magnetic resonance brain scan revealed T2 hyperintense punctiform lesions in the stem, cerebellum, diencephalons and cortico-subcortical areas of both hemispheres, which were enhanced with contrast. An aetiological study was performed to rule out any underlying infectious, neoplastic or inflammatory origin, the results being negative. The patient was treated on two occasions with methylprednisolone, with a gradual lowering of the dosage, the response being favourable. Conclusions. Diplopia and ataxia, as in our case, are practically always present. The MR findings consist of punctiform enhancing lesions located in the pons extending towards the cerebellum, basal ganglia and corpus callosum, the enhancement gradient becoming lower as the distance increases rostrally away from the cortex, and caudally towards the spinal cord. In the case of our patient, this gradient is not respected, and the density found was similar to that of lesions at the supratentorial level. The differential diagnosis is wide-ranging and justifies an extensive diagnostic study with, in certain cases, a biopsy study of brain tissue. The disease courses in a relapsing-remitting pattern and the earlier steroid therapy is established and the more prolonged it is, the better the prognosis will b

Cost-Analysis of Subcutaneous vs Intravenous Administration of Natalizumab Based on Patient Care Pathway in Multiple Sclerosis in Spain

Análisis de costes; Administración subcutánea; Esclerosis múltipleAnàlisi de costos; Administració subcutània; Esclerosi múltipleCost-analysis; Subcutaneous administration; Multiple sclerosisIntroduction A subcutaneous (SC) formulation of natalizumab has been recently authorised for multiple sclerosis patients. This study aimed to assess the implications of the new SC formulation, and to compare the annual treatment costs of SC versus intravenous (IV) natalizumab therapy from both the Spanish healthcare system (direct health cost) and the patient (indirect cost) perspectives. Methods A patient care pathway map and a cost-minimisation analysis were developed to estimate SC and IV natalizumab annual costs over a 2-year time horizon. Considering the patient care pathway and according to natalizumab experience (IV) or estimation (SC), a national expert panel involving neurologists, pharmacists, and nurses provided information/data regarding resource consumption for drug and patient preparation, administration, and documentation. One hour of observation was applied to the first six (SC) or 12 (IV) doses, and 5 min for successive doses. The Day hospital (infusion suite) facilities at a reference hospital were considered for IV administrations and the first six SC injections. For successive SC injections, either a reference hospital or regional hospital in a consulting room was considered. Productivity time associated with travel (56 min to reference hospital, 24 min to regional hospital) and waiting time pre- and post-treatment (SC 15 min, IV 25 min) were assessed for patients and caregivers (accompanying 20% of SC and 35% of IV administrations). National salaries for healthcare professionals were used for cost estimation (€, year 2021). Results At years 1 and 2, total time and cost savings (excluding drug acquisition cost) per patient, driven by saving on administration and patient and caregiver productivity for SC at a reference hospital versus IV at a reference hospital, were 116 h (a reduction of 54.6%) and €3682.82 (a reduction of 66.2%). In the case of natalizumab SC at a regional hospital, the total time and cost saving were 129 h (a reduction of 60.6%) and €3883.47 (a reduction of 69.8%). Conclusions Besides the potential benefits of convenient administration and improving work–life balance, as suggested by the expert panel, natalizumab SC was associated with cost savings for the healthcare system by avoiding drug preparation, reducing administration time, and freeing up infusion suite capacity. Additional cost savings could be derived with regional hospital administration of natalizumab SC by reducing productivity loss

Impact of Neuromyelitis Optica Spectrum Disorder on Quality of Life from the Patients' Perspective : An Observational Cross-Sectional Study

Altres ajuts: Medical Department of Roche Farma, Spain (ML41397).Introduction: Neuromyelitis optica spectrum disorder (NMOSD) is associated with a reduced health-related quality of life (HRQoL). The purpose of this study was to describe the impact of NMOSD on HRQoL from the patients' perspective and its relationship with other disease factors. Methods: An observational, cross-sectional study was conducted at 13 neuroimmunology clinics in Spain. Patients with NMOSD diagnosis (2015 Wingerchuk criteria) were included. The 29-item Multiple Sclerosis Impact Scale (MSIS-29) was used to assess the HRQoL. Different questionnaires were used to measure symptom severity, stigma, mood disorders, pain, fatigue, and difficulties in the workplace. Factors that impact HRQoL were identified by Spearman's correlation and multivariate linear regression analysis. Results: Seventy-one patients were included (mean age 47.4 ± 14.9 years, 80.3% female, mean time since disease onset 9.9 ± 8.1 years). The median Expanded Disability Status Scale score was 3.0 (1.5-4.5). The mean (± SD) physical and psychological MSIS-29 sub-scores were 41.9 ± 16.8 and 20.9 ± 8.3, respectively. Fatigue and body pain were the most prevalent symptoms. Depressive symptoms were found in 44.3% (n = 31) of patients. The physical MSIS-29 dimension showed the highest correlation with symptom severity (ρ = 0.85584, p < 0.0001), whereas the highest correlations for psychological MSIS-29 dimension were pain, MSIS-29 physical dimension, and depression (ρ = 0.76487, 0.72779, 0.71380; p < 0.0001, respectively). Pain was a predictor of both dimensions of MSIS-29. Conclusion: Fatigue, pain, and depressive symptoms are frequent problems among patients with NMOSD, impacting on their quality of life. Assessment of patient-oriented outcomes may be useful to achieve a holistic approach, allowing early specific interventions

Quantifying the patient´s perspective in neuromyelitis optica spectrum disorder: Psychometric properties of the SymptoMScreen questionnaire

Background: The assessment of self-reported outcomes in neuromyelitis optica spectrum disorder (NMOSD) is limited by the lack of validated disease-specific measures. The SymptoMScreen (SyMS) is a patient-reported questionnaire for measuring symptom severity in different domains affected by multiple sclerosis (MS), but has not been thoroughly evaluated in NMOSD. The aim of this study was to assess the psychometric properties of the SyMS in a sample of patients with NMOSD. Methods: A non-interventional, cross-sectional study in adult subjects with NMOSD (Wingerchuk 2015 criteria) was conducted at 13 neuroimmunology clinics applying the SyMS. A non-parametric item response theory procedure, Mokken analysis, was performed to assess the underlying dimensional structure and scalability of items and overall questionnaire. All analyses were performed with R (v4.0.3) using the mokken library. Results: A total of 70 patients were studied (mean age: 47.5 ± 15 years, 80% female, mean Expanded Disability Status Scale score: 3.0 [interquartile range 1.5, 4.5]). Symptom severity was low (median SyMS score: 19.0 [interquartile range 10.0, 32.0]). The SyMS showed a robust internal reliability (Cronbach's alpha: 0.90 [95% confidence interval 0.86, 0.93]) and behaved as a unidimensional scale with all items showing scalability coefficients > 0.30. The overall SyMS scalability was 0.45 conforming to a medium scale according to Mokken's criteria. Fatigue and body pain were the domains with the highest scalability coefficients. The SyMS was associated with disability (rho: 0.586), and physical and psychological quality of life (rho: 0.856 and 0.696, respectively). Conclusions: The SyMS shows appropriate psychometric characteristics and may constitute a valuable and easy-to-implement option to measure symptom severity in patients with NMOSD

Perception of Stigma in Patients with Neuromyelitis Optica Spectrum Disorder

Background: Perception of stigma was associated with low self-esteem, psychological problems, and decreased health-seeking behavior among patients with different neurological disorders. The purpose of this study was to assess stigmatization and its impact in patients with neuromyelitis optica spectrum disorder (NMOSD). Methods: A non-interventional study was conducted at thirteen neuroimmunology clinics in Spain. Patients with a diagnosis of NMOSD (2015 Wingerchuk criteria) were included. The 8-item Stigma Scale for Chronic Illness (SSCI-8), the Expanded Disability Status Scale (EDSS), the 29-item Multiple Sclerosis Impact Scale (MSIS-29), the Beck Depression Inventory-Fast Screen (BDI-FS), the MOS Pain Effects Scale (MOS-PES) and the Fatigue Impact Scale for Daily Use (D-FIS) were used to assess the perception of stigma, disability, quality of life, mood, pain, and fatigue, respectively. Associations between outcome measures were analyzed using Spearman's rank correlation. Results: Seventy-one patients were studied (mean age: 47.4 years ± 14.9, 81.7% female, mean time since disease onset: 9.9 years ± 8.1). The median EDSS score was 3.0 (interquartile range 1.5, 4.5). Stigma prevalence was 61.4% (n=43). Thirty-one patients (43.6%) had depression. The SSCI-8 score showed a significant correlation with both physical (rho=0.576, p<0.0001) and psychological (rho=0.608, p<0.0001) MSIS-29 scales scores, EDSS score (rho=0.349, p=0.0033), BDI-FS score (rho= 0.613, p<0.0001), MOS-PES score (rho= 0.457, p<0.0001), and D-FIS score (rho=0.556, p<0.0001). Conclusion: Stigma is a common phenomenon affecting over 6 out of 10 patients with NMOSD. Understanding stigma may be useful to develop educational strategies improving NMOSD knowledge

Expert-Agreed Practical Recommendations on the Use of Cladribine

Cladribine; Disease-modifying drugs; Relapsing multiple sclerosisCladribina; Medicaments modificadors de malalties; Esclerosi múltiple recurrentCladribina; Medicamentos modificadores de enfermedades; Esclerosis múltiple recurrenteCladribine is a disease-modifying selective immune reconstitution oral therapy for adult patients with highly active relapsing multiple sclerosis (RMS). It was approved in the USA in 2019 and in Europe in 2017, thus there are still gaps in existing guidelines for using cladribine tablets in clinical practice. Nine experts with extensive experience in managing patients with multiple sclerosis in Spain identified some of the unanswered questions related to the real-life use of cladribine tablets. They reviewed the available clinical trial data and real-world evidence, including their own experiences of using cladribine, over the course of three virtual meetings held between November 2020 and January 2021. This article gathers their practical recommendations to aid treatment decision-making and optimise the use of cladribine tablets in patients with RMS. The consensus recommendations cover the following areas: candidate patient profiles, switching strategies (to and from cladribine), managing response to cladribine and safety considerations.The publication of this article, as well as journal’s Rapid Service Fee, was funded by Merck, S.L.U., Mollet del Valles, Spain, an affiliate of Merck KGaA

Neuromyelitis optica spectrum disorders. Comparison according to the phenotype and serostatus

Objective: To (1) determine the value of the recently proposed criteria of neuromyelitis optica (NMO) spectrum disorder (NMOSD) that unify patients with NMO and those with limited forms (NMO/LF) with aquaporin-4 immunoglobulin G (AQP4-IgG) antibodies; and (2) investigate the clinical significance of the serologic status in patients with NMO. Methods: This was a retrospective, multicenter study of 181 patients fulfilling the 2006 NMO criteria (n = 127) or NMO/LF criteria with AQP4-IgG (n = 54). AQP4-IgG and myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG) antibodies were tested using cell-based assays. Results: Patients were mainly white (86%) and female (ratio 6.5:1) with median age at onset 39 years (range 10-77). Compared to patients with NMO and AQP4-IgG (n = 94), those with NMO/LF presentedmore often with longitudinally extensive transverse myelitis (LETM) (p<0.001), and had lower relapse rates (p = 0.015), but similar disability outcomes. Nonwhite ethnicity and optic neuritis presentation doubled the risk for developing NMO compared with white race (p = 0.008) or LETM presentation (p = 0.008). Nonwhite race (hazard ratio [HR] 4.3, 95% confidence interval [CI] 1.4-13.6) and older age at onset were associated with worse outcome (for every 10-year increase, HR 1.7, 95% CI 1.3-2.2). Patients with NMO and MOG-IgG (n = 9) had lower female: male ratio (0.8:1) and better disability outcome than AQP4-IgG-seropositive or double-seronegative patients (p<0.001). Conclusions: In patients with AQP4-IgG, the similar outcomes regardless of the clinical phenotype support the unified term NMOSD; nonwhite ethnicity and older age at onset are associated with worse outcome. Double-seronegative and AQP4-IgG-seropositive NMO have a similar clinical outcome. The better prognosis of patients with MOG-IgG and NMO suggests that phenotypic and serologic classification is useful