Effectiveness of autologous haematopoietic stem cell transplantation versus natalizumab in progressive multiple sclerosis.

BACKGROUND: Natalizumab was not shown to modify disability in progressive multiple sclerosis (MS). This matched observational study compared the effectiveness of autologous haematopoietic stem cell transplantation (AHSCT) with natalizumab in progressive MS. METHODS: Patients with primary/secondary progressive MS from seven AHSCT MS centres and the MSBase registry, treated with AHSCT or natalizumab, were matched on a propensity score derived from sex, age, Expanded Disability Status Scale (EDSS), number of relapses 12/24 months before baseline, time from MS onset, the most effective prior therapy and country. The pairwise-censored groups were compared on hazards of 6-month confirmed EDSS worsening and improvement, relapses and annualised relapse rates (ARRs), using Andersen-Gill proportional hazards models and conditional negative binomial model. RESULTS: 39 patients treated with AHSCT (37 with secondary progressive MS, mean age 37 years, EDSS 5.7, 28% with recent disability progression, ARR 0.54 during the preceding year) were matched with 65 patients treated with natalizumab. The study found no evidence for difference in hazards of confirmed EDSS worsening (HR 1.49, 95% CI 0.70 to 3.14) and improvement (HR 1.50, 95% CI 0.22 to 10.29) between AHSCT and natalizumab over up to 4 years. The relapse activity was also similar while treated with AHSCT and natalizumab (ARR: mean±SD 0.08±0.28 vs 0.08±0.25; HR 1.05, 95% CI 0.39 to 2.82). In the AHSCT group, 3 patients experienced febrile neutropenia during mobilisation, 9 patients experienced serum sickness, 6 patients required intensive care unit admission and 36 patients experienced complications after discharge. No treatment-related deaths were reported. CONCLUSION: This study does not support the use of AHSCT to control disability in progressive MS with advanced disability and low relapse activity.

Spinal cord size as promising biomarker of disability outcomes after hematopoietic stem cell transplantation in multiple sclerosis.

BACKGROUND: Biomarkers predictive of disability outcomes in individual multiple sclerosis (MS) patients undergoing autologous haematopoietic stem cell transplantation (AHSCT) are currently lacking. As correlations between spinal cord atrophy and clinical disability in MS were previously described, in this study spinal cord size was investigated in MS patients treated with AHSCT, exploring whether baseline spinal cord volume may predict disability progression after AHSCT. METHODS: relapsing-remitting (RR-) and secondary-progressive (SP-) MS patients treated with AHSCT (BEAM/ATG regimen) at a single academic centre in Florence, who performed at least two standardized brain magnetic resonance imaging (MRIs) scans (acquired between one-year pre-AHSCT to 5 years after AHSCT) were included. Cervical spinal cord atrophy was estimated as upper cervical spinal cord cross-sectional area (SCCSA). Brain volume loss (BVL) was analysed at the same timepoints. RESULTS: Eleven (8 RR-; 3 SP-) MS patients were included. Over a median follow-up of 66 (range 37 - 100) months, no relapses nor brain MRI activity were observed; disability progressed in 2 cases (both SP-MS). Baseline SCCSA was associated with EDSS change between pre- and one-year post-AHSCT. Compared to patients who stabilized, patients who progressed after AHSCT tended to have lower SCCSA at C4 level at baseline and year 1 after AHSCT. Longitudinal changes in SCCSA or BVL did not correlate with EDSS change. CONCLUSIONS: Baseline pre-AHSCT SCCSA, but not its longitudinal changes nor BVL, predicted EDSS change within the two years following AHSCT. SCCSA may represent a biomarker of treatment response and a promising screening tool for assessing patient eligibility for high-impact treatments such as AHSCT.

Efficacy of intrathecal mesenchymal stem cell-neural progenitor therapy in progressive MS: results from a phase II, randomized, placebo-controlled clinical trial.

BACKGROUND: Mesenchymal stem cell-neural progenitors (MSC-NPs) are a bone marrow mesenchymal stem cell (MSC)-derived ex vivo manipulated cell product with therapeutic potential in multiple sclerosis (MS). The objective of this study was to determine efficacy of intrathecal (IT) MSC-NP treatment in patients with progressive MS. METHODS: The study is a phase II randomized, double-blind, placebo-controlled clinical trial with a compassionate crossover design conducted at a single site. Subjects were stratified according to baseline Expanded Disability Status Scale (EDSS) (3.0-6.5) and disease subtype (secondary or primary progressive MS) and randomized into either treatment or placebo group to receive six IT injections of autologous MSC-NPs or saline every two months. The primary outcome was EDSS Plus, defined by improvement in EDSS, timed 25-foot walk (T25FW) or nine-hole peg test. Secondary outcomes included the individual components of EDSS Plus, the six-minute walk test (6MWT), urodynamics testing, and brain atrophy measurement. RESULTS: Subjects were randomized into MSC-NP (n = 27) or saline (n = 27) groups. There was no difference in EDSS Plus improvement between the MSC-NP (33%) and saline (37%) groups. Exploratory subgroup analysis demonstrated that in subjects who require assistance for ambulation (EDSS 6.0-6.5) there was a significantly higher percentage of improvement in T25FW and 6MWT in the MSC-NP group (3.7% ± 23.1% and - 9.2% ± 18.2%) compared to the saline group (-54.4% ± 70.5% and - 32.1% ± 30.0%), (p = 0.030 and p = 0.036, respectively). IT-MSC-NP treatment was also associated with improved bladder function and reduced rate of grey matter atrophy on brain MRI. Biomarker analysis demonstrated increased MMP9 and decreased CCL2 levels in the cerebrospinal fluid following treatment. CONCLUSION: Results from exploratory outcomes suggest that IT-MSC-NP treatment may be associated with a therapeutic response in a subgroup of MS patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT03355365, registered November 14, 2017, https://clinicaltrials.gov/study/NCT03355365?term=NCT03355365&rank=1 .

Consenso sobre la identificación y seguimiento de la esclerosis múltiple secundaria progresiva en Argentina / Argentinean consensus guidelines on the identification and clinical care of secondary progressive multiple sclerosis

INTRODUCCIÓN: Existen diferencias significativas en el diagnóstico, la identificación y el seguimiento de pacientes con esclerosis múltiple secundaria progresiva (EMSP) entre los profesionales de la salud a cargo de su tratamiento. OBJETIVO: Proveer recomendaciones sobre el tratamiento de los pacientes con EMSP en Argentina con el fin de optimizar su cuidado. DESARROLLO: Un grupo de neurólogos expertos en esclerosis múltiple de Argentina elaboró un consenso para el tratamiento de pacientes con EMSP en la región mediante metodología de ronda de encuestas a distancia y reuniones presenciales. Se establecieron 33 recomendaciones basadas en la evidencia publicada y en el criterio de los expertos que participaron. Las recomendaciones se enfocaron en el diagnóstico y el seguimiento de los pacientes con EMSP. CONCLUSIÓN: Las recomendaciones establecidas en el presente consenso permitirían optimizar el cuidado y el seguimiento de los pacientes con EMSP en Argentina

INTRODUCTION: The identification, diagnosis, follow-up, and treatment of patients with secondary progressive multiple sclerosis (SPMS) show significant differences between health care professionals in Argentina. AIM: To provide consensus recommendations on the management of patients with SPMS in Argentina to optimize patient care. DEVELOPMENT: A panel of expert neurologists from Argentina dedicated to the diagnosis and care of multiple sclerosis patients gathered during 2019 and 2020 to carry out a consensus recommendation on the diagnosis and treatment of SPMS patients in Argentina. To achieve consensus, the methodology of formal consensus-RAND/UCLA method was used. Recommendations were established based on published evidence and the expert opinion. Recommendations focused on how to define SPMS and how to follow SPMS patients. CONCLUSION: The recommendations of this consensus guidelines attempt to optimize the care of SPMS patients in Argentina

Experiencia del tratamiento con interferón B en la esclerosis múltiple en Galicia / Experience in the treatment of multiple of multiple sclerosis with interferón beta in Galicia

Objetivo. Analizar la experiencia en la práctica clínica diaria del tratamiento con interferón b (IFN b) en la esclerosis múltiple (EM) remitenterecidivante (RR) y secundaria progresiva (SP) en Galicia. Pacientes y métodos. Se analizaron los datos clínicos y demográficos de pacientes con EM RR y EM SP tratados con IFN b 1a y 1b entre 1995 y diciembre de 2000. Resultados. Se incluyeron 313 pacientes, con una media de edad de 38,2 años. Un total de 296 caso (94,6%) fueron EM clínicamente definidos y 17 (5,4%) fueron EM apoyados por laboratorio (criterios Poser); el 84,6% de los pacientes padecían EM RR y el 15,4%, EM SP. La duración media de la enfermedad antes del tratamiento fue 7,06 años. Se empleó Betaferón â en el 52,4% de los pacientes (115 EM RR y 47 EM SP), Avonex â en el 26% y Rebif â en el 21,6%. La tasa de brotes se redujo en un 68,8% para la EM RR en los pacientes tratados con Betaferón, en un 73,3% en los tratados con Avonex y en un 35,7% en los tratados con Rebif. El Betaferón redujo la tasa de brotes en un 50% para la EM SP. Durante el tratamiento, el EDSS global permaneció estable, y el 33% de los pacientes tratados con Betaferón, el 60,5% de los tratados con Avonex y el 54,5% de los tratados con Rebif permanecieron libres de brotes. El tratamiento se suspendió en el 12,9% de los pacientes tratados con Betaferón, el 6,2% de los tratados con Avonex, y el 3% de los tratados con Rebif, y las causas más frecuentes fueron el incremento de la discapacidad y el aumento de brotes. Conclusiones. Este estudio apoya el beneficio del tratamiento con IFN b en la EM RR y la EM SP en la práctica clínica diaria, pues promueve la reducción de los brotes, la tasa de brotes y la discapacidad, con una buena tolerancia global y una baja incidencia de efectos secundarios graves (AU)

Objective. To analyze the experience in daily clinical practice of interferonbeta (IFN b) treatment in relapsing remitting (RR) and secondary progressive (SP) multiple sclerosis (MS) in Galicia (Spain). Patients and methods. Patients with RRMS and SPMS treated with IFN b 1a and 1b between 1995 and December/2000, analyzing demographic and clinical data. Results. 313 patients were included, with a mean age of 38,2 years. A total of 296 patients (94,6%) were clinically defined MS and 17 (5,4%) were laboratory supported (Poser criteria); 84,6% of the patients were RR and 15,4% were SP. The mean duration of the disease prior to treatment was 7,06 years. Betaferon â was used in 52,4% patients (115 RRMS and 47 SPMS), Avonex â in 26% and Rebif â in 21,6%. Relapse rate was reduced in 68,8% for the RRMS for Betaferontreated patients, 73,3% for Avonex treated and 35,7% for ebiftreated patients. Betaferon reduced relapse rate in 50% for SPMS. The global EDSS remained stable during IFN b treatment. During treatment, 33% of Betaferon, 60,5% of Avonex and 54,5% of Rebiftreated patients remained relapsefree. Treatment was suspended in 12,9% of Betaferon, 6,2% of Avonex, and 3% Rebiftreated patients. The most frequent causes of treatment suspension were increase in disability and in relapse count. Conclusions. The present study supports the benefits of IFN b treatment in RR MS and SP MS in daily clinical practice, with reduction in relapses count and discapacity, good overall tolerance and low incidence of serious adverse sideeffects (AU)