Search

Background: Dimethyl fumarate (DMF) has demonstrated efficacy in phase III studies. However, real-world data are still limited. Objective: The objective of this study was to describe the profile of patients who receive DMF and to assess the effectiveness of DMF regarding relapses, disability progression, magnetic resonance imaging activity, and NEDA (No Evidence Disease Activity)-3 status in a Spanish population in a real-world setting. Methods: We conducted a multicenter prospective study of patients who started DMF between 2014 and 2019 in Spain. Three subgroups were considered: naïve, switch to DMF because of inefficacy, and switch to DMF because of adverse effects. The effects of DMF on clinical and radiological measures were evaluated. Results: Among 886 patients, 25.3% were naïve, 28.8% switched because of adverse effects, and 45.9% because of inefficacy. Median follow-up was 38.9 (interquartile range 22.6–41.8) months. Annualized relapse rates were 0.15, 0.10, and 0.10 at 12, 24, and 36 months respectively, and 77.7% of patients were relapse free at month 42. At 12, 24, and 42 months, 96.1%, 87.4%, and 79.7% of patients were progression free, respectively. The number of T1 gadolinium-enhancement (T1Gd+) lesions was 0.19, 0.14, and 0.18 at 12, 24, and 36 months. NEDA-3 status at month 42 was maintained by 49.8% of patients. Relapsing was associated with higher annualized relapse rates the year before (hazard ratio 1.34, p < 0.001) and to the inefficacy switch vs naïve group (hazard ratio 1.76, p = 0.003). A higher baseline Expanded Disability Status Scale score was associated with disability progression (hazard ratio 1.15, p = 0.003) and more T1Gd+ lesions (hazard ratio 1.07, p < 0.001) with radiological progression. A higher baseline Expanded Disability Status Scale score, a larger number of T1Gd+ lesions, and a switch because of inefficacy (vs adverse events) were all risk factors for losing NEDA-3 status. DMF was discontinued in 29.9% of patients, in 13.5% because of inefficacy. Conclusions: Our findings confirm the sustained effectiveness of DMF on the clinical and radiological activity of multiple sclerosis in a real-world setting, both in naïve patients and in those switching from other multiple sclerosis therapies. [ABSTRACT FROM AUTHOR]

Background: Dimethyl fumarate (DMF) tolerability and safety in multiple sclerosis (MS) has been analyzed in randomized clinical trials. Real-life studies are needed to assess possible harms of this therapy in a wider MS population. Objective: To evaluate DMF tolerability, safety and persistence in MS in a real-world setting. Methods: We conducted a multicenter prospective study of patients who started DMF, attended in 16 public hospitals of Spain. A specific database was elaborated to collect data on most frequent adverse events (AE). Regression models were used to analyze the effect of demographic and clinical characteristics on risk of AEs and DMF discontinuation. Results: We collected data of 886 patients (2681 patients/years-exposition) with median 39.5 (IQR 23, 51.5) months on DMF exposure; 25.3% were treatment naïve and 74.7% switched to DMF from other disease-modifying therapies. DMF was discontinued in 29.9% of patients, in 13.2% due to AEs and in 13.5% to inefficacy. AEs were experienced by 71.2%, being flushing the most frequent (44.1%), 5.4% developed grade III lymphopenia, without cases of grade IV. Females showed a higher risk of flushing and gastroenteric symptoms (OR 1.49, p = 0.011; OR 1.69, p = 0.001, respectively); lymphopenia was associated with older age (OR 1.04, p < 0.001), and a higher EDSS with lymphopenia (OR 1.10, p = 0.035) and DMF withdrawal (HR 1.43, p = 0.012). No safety problems were reported. Conclusions: Our findings confirm good tolerability and safety of DMF in real-world setting and suggest that women have an increased risk of AEs and higher baseline disability involves greater risk of drug discontinuation. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this study was to characterize the demographic and clinical profile of RRMS patients receiving fingolimod in Spain, and to evaluate drug effectiveness and safety in clinical practice. Methods: This observational, retrospective, multicentre, nationwide study was performed at 56 Spanish hospitals and involved 804 RRMS patients who received oral fingolimod (0.5 mg) since November 2011, with a minimum follow-up of 12 months. Results: The mean annualized relapse rate (ARR) in the year before fingolimod was 1.08 and the median EDSS was 3; patients were exposed to fingolimod for 2.2 years as average; regarding magnetic resonance imaging (MRI) activity, more than half of the patients had >20 lesions at baseline. Patients were previously treated with first-line injectable DMTs (60.3%), or natalizumab (31.3%), and 8.3% were naïve patients. Overall, the ARR significantly decreased to 0.28, 0.22 and 0.17 (74.1%, 79.7% and 83.5% of relative reduction, respectively) after 12, 24 and 36 months of treatment, P<0.001. The ARR of patients who switched from natalizumab to fingolimod was stable over the study. Most of the patients (88.7%) were free from confirmed disability and MRI activity (67.3%) after 24 months. The persistence after 12 months on fingolimod was 93.9%. Conclusions: The subgroups of patients analysed showed differential baseline demographic and clinical characteristics. The analysis of patients who received fingolimod in routine clinical practice confirmed adequate efficacy and safety, even for long-term treatment. The present data also confirmed the positive benefit/risk balance with fingolimod in real-world clinical practice setting. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is primarily an inflammatory and degenerative disease of the central nervous system, triggered by unknown environmental factors in patients with predisposing genetic risk profiles. The prevention of neurological disability is one of the essential goals to be achieved in a patient with MS. However, the pathogenic mechanisms driving the progressive phase of the disease remain unknown. It was described that the pathophysiological mechanisms associated with disease progression are present from disease onset. In daily practice, there is a lack of clinical, radiological, or biological markers that favor an early detection of the disease's progression. Different definitions of disability progression were used in clinical trials. According to the most descriptive, progression was defined as a minimum increase in the Expanded Disability Status Scale (EDSS) of 1.5, 1.0, or 0.5 from a baseline level of 0, 1.0-5.0, and 5.5, respectively. Nevertheless, the EDSS is not the most sensitive scale to assess progression, and there is no consensus regarding any specific diagnostic criteria for disability progression. This review document discusses the current pathophysiological concepts associated with MS progression, the different measurement strategies, the biomarkers associated with disability progression, and the available pharmacologic therapeutic approaches., Competing Interests: VM-L has received compensation for consulting services and speaking honoraria from Almirall, Biogen, Genzyme, Merck Serono, Novartis, Roche, Terumo, Sanofi and Teva. LB-R has received compensation for consulting services and speaking honoraria from Biogen, Sanofy-Genzyme, Merck Serono, Novartis, Roche, and Teva. JC-P has received compensation for consulting services from Roche. SE-M has received compensation for consulting services and speaking honoraria from Biogen Idec, Novartis, Merck, Bayer, Sanofi-Genzyme, Roche, and Teva. JF-L has received compensation for consulting services from Roche. LF has received compensation for consulting services from Roche, Merck, Novartis and Genzyme, for speaking honoraria from Roche, Merck and Novartis, and for traveling grants from Genzyme, Roche and Novartis. YH has received compensation for consulting services from Roche and Merck, Novartis, Teva and Genzyme, for speaking, honoraria from Roche, Merck and Novartis, and for traveling grants from Merck, Genzyme, Roche and Novartis. NT has received compensation for consulting services, traveling grants and speaking honoraria from Bayer Schering Pharma, Biogen Idec, Merck Serono, Novartis, Sanofi-Aventis, Teva, and Roche. AV-J has received investigation grants Juan Rodes (JR16/00024) from Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, and has received compensation for consulting services, participation in advisory boards, and speaking honoraria from Novartis, Stendhal, Roche, Teva, Biogen, and Genzyme-Sanofi. FP-M has received compensation for consulting services and speaking honoraria from Roche, Sanofi-Genzyme y Biogen, and speaking honoraria from Novartis, Almirall and Teva., (Copyright © 2021 Meca-Lallana, Berenguer-Ruiz, Carreres-Polo, Eichau-Madueño, Ferrer-Lozano, Forero, Higueras, Téllez Lara, Vidal-Jordana and Pérez-Miralles.)

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 presented more 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.

Introduction: 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 be.