Deciphering Multiple Sclerosis Progression.

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.

Real-world experience of ocrelizumab in multiple sclerosis in a Spanish population.

OBJECTIVE: Pivotal trial have shown that patients with multiple sclerosis (MS) receiving ocrelizumab had better outcomes. However, data on ocrelizumab in clinical practice are limited. The aim of this study was to evaluate the preliminary safety profile and effectiveness of ocrelizumab treatment for multiple sclerosis (MS) in a real-world clinical setting. METHODS: We conducted a retrospective study including consecutive patients from nine public hospitals in south-eastern Spain who received ocrelizumab after it was approved. RESULTS: A total of 228 MS patients were included (144 with relapsing-remitting MS [RRMS], 25 secondary progressive MS [SPMS], and 59 primary progressive MS [PPMS]). Median follow-up period was 12 months (range, 1-32). No evidence of disease activity (NEDA) status at year 1 was achieved in 91.2% of the relapsing MS (RMS) population, while disability progression was detected in 37.5% of the PPMS patients (median follow-up period, 19 months). The most common adverse events reported were infusion-related reactions and infections, with the most common infections being urinary tract infections followed by upper respiratory infections and COVID-19. INTERPRETATION: The preliminary results in our real-world setting show that ocrelizumab presented excellent results in suppressing disease activity with a favorable and consistent safety profile.

Ocrelizumab in Multiple Sclerosis: A Real-World Study From Spain.

Objectives: The aim of this study was to describe the tolerability, safety, and effectiveness of ocrelizumab for primary progressive multiple sclerosis (PPMS) and relapsing multiple sclerosis (RMS) in a clinical practice setting. Methods: In this retrospective observational study, we analyzed clinical and MRI data in all patients with PPMS and RMS who had received at least one infusion of ocrelizumab in two health areas in south-eastern Spain. Patients involved in any ocrelizumab trial and those patients with a follow-up shorter than 6 months were excluded. Results: The cohort included 70 patients (42 women) who had received ocrelizumab; 30% had PPMS and 70%, RMS. At baseline, patients' mean age was 47.1 years in the PPMS group and 39.2 years in the RMS group, while the median EDSS was 3.0 and 2.5, respectively. Median follow-up was 13.6 months. The median number of treatment cycles was three. Most patients remained free from clinical and MRI activity after ocrelizumab initiation. Baseline MRI showed T1 Gd-enhancing lesions in 57% of the patients; by the first MRI control at 4-6 months, all patients except one were free of T1 Gd-enhancing lesions (69/70, 98.6% P < 0.001). The proportion of patients with NEDA was 94% in the group of RMS patients who were followed for at least 1 year. Ocrelizumab was generally well-tolerated; the most common adverse events were infusion-related reactions and infections, none of which were serious. Conclusions: Our real-world study supports the tolerability, safety, and effectiveness of ocrelizumab in clinical practice.

Relapses and obstetric outcomes in women with multiple sclerosis planning pregnancy.

OBJECTIVE: To evaluate the effect of discontinuation of different disease-modifying therapies (DMTs) before pregnancy with respect to the occurrence of relapses and pregnancy outcomes. METHODS: Women with multiple sclerosis who desire to bear children were followed prospectively. Demographic data, clinical characteristics, and the information on the use of DMTs were collected. A multivariate analysis was used to assess the relationship between relapses and the prior use of different DMTs. RESULTS: The present study assessed 75 consecutive pregnancy plans (66 women), 65 of which resulted in pregnancy. The mean age of the participants was 32.1 ± 4.2 years, and the mean disease duration was 6.1 ± 4.2 years. No relapses before pregnancy were reported in the group of women who maintained their DMT until pregnancy confirmation, while 14 relapses were reported in 12/42 women (29%) who discontinued DMT before pregnancy. During pregnancy, patients on natalizumab or fingolimod before pregnancy had a higher rate of relapses. Most women restarted their previous DMT after delivery within the first trimester. The relapse rate in postpartum was 0.07. CONCLUSIONS: Disease-modifying therapies received influences the risk of relapse and disease progression from women who are planning pregnancy. The risk of relapse during pregnancy was significantly higher in the group of women treated with natalizumab or fingolimod compared to the group of women treated with interferon beta or glatiramer acetate. The postpartum risk of relapses was lower than that found in previous reports.

Rescue Therapy Using Rituximab for Multiple Sclerosis.

OBJECTIVES: The aim of the study was to describe the effectiveness and safety data of rituximab in a group of patients with relapsing-remitting multiple sclerosis (MS) treated with rituximab due to failure of previous treatments or concomitant autoimmune diseases. METHODS: This is an observational study. Rituximab was considered in case of failure of the second-line therapy, failure of the first-line therapy and a contraindication to second-line therapies, or concomitant autoimmune disease. Relapses, the Expanded Disability Status Scale, the EQ VAS, and magnetic resonance imaging activity were assessed. RESULTS: This study included 12 patients with relapsing-remitting MS. The mean (range) age of the patients was 35 (19-54) years. Ten patients were treated with rituximab because of treatment failure, and 2 patients were treated with rituximab because of the development of idiopathic thrombocytopenic purpura. The mean (range) follow-up duration after beginning rituximab was 40 (18-72) months. Rituximab was well tolerated, because no patient experienced serious adverse reactions or discontinued treatment. During treatment with rituximab, no patient suffered a clinical relapse, and magnetic resonance imaging activity was not detected. The Expanded Disability Status Scale scores improved in 11 of 12 patients and remained stable in 1 patient. The EuroQol visual analogue scale scores improved in 8 of 9 patients in whom the EuroQol visual analogue scale was assessed. CONCLUSIONS: Treatment with rituximab seems to be safe and effective for some patients with relapsing-remitting MS who have failed to respond to first- and second-line therapies and may also be a useful option for patients with concomitant autoimmune disorders.

Changes in mechanical, chemical, and thermal sensitivity of the cornea after topical application of nonsteroidal anti-inflammatory drugs.

PURPOSE: In addition to their well-known anti-inflammatory actions, some of the nonsteroidal anti-inflammatory drugs (NSAIDs) appear to have an analgesic effect. In human subjects, the changes in threshold and intensity of sensations evoked by mechanical, chemical, and thermal stimulation of the cornea induced by topical administration of two commercial NSAIDs, diclofenac sodium (Voltaren; Novartis, Basel, Switzerland) and flurbiprofen (Ocuflur; Allergan, Irvine, CA), were studied. METHODS: Corneal sensitivity was measured in 10 young, healthy subjects with a gas esthesiometer. Chemical (10%-70% CO2 in air), mechanical (0-264 mL/min), and thermal (corneal temperature changes between -4.5 degrees C and +3 degrees C around the normal value) stimuli were applied to the center of the cornea. The intensity and perceived magnitude of the psychophysical attributes of the evoked sensation were scored at the end of the pulse in a 10-cm, continuous visual analog scale (VAS). The threshold was expressed as the stimulus intensity that evoked a VAS score >0.5. Sensitivity was measured in both eyes of each subject on two separate days, one without treatment and the other 30 minutes after topical application of 0.03% flurbiprofen (seven subjects) or 0.1% diclofenac sodium (six subjects). RESULTS: Diclofenac attenuated significantly all the sensation parameters evoked by high-intensity mechanical, chemical, and thermal stimuli. Flurbiprofen produced a slight reduction of the sensations evoked by mechanical and chemical stimulation that became significant only for the irritation caused by chemical stimuli of maximum intensity (70% CO2). None of the drugs modified significantly the detection threshold of the different stimuli. CONCLUSIONS: Flurbiprofen had a very limited effect on sensations evoked by corneal stimulation, whereas diclofenac reduced the intensity of sensations evoked by stimuli of different modality, suggesting a mild local anesthetic effect of this drug on all types of corneal sensory fibers. Such anesthetic action could explain the analgesic effect that has been reported after topical application of diclofenac in inflamed human eyes.

Fingolimod: efectividad y seguridad en la práctica clínica habitual. Estudio observacional, retrospectivo y multicéntrico en la provincia de Alicante / Fingolimod: effectiveness and safety in routine clinical practice. An observational, retrospective, multi-centre study in the province of Alicante

INTRODUCCIÓN: Los estudios postautorización son importantes para confirmar si los resultados de los ensayos clínicos se reproducen en la práctica clínica habitual. OBJETIVO: Evaluar la efectividad y seguridad del fingolimod en la práctica clínica en la provincia de Alicante. PACIENTES Y MÉTODOS: Estudio multicéntrico retrospectivo de pacientes con esclerosis múltiple remitente tratados con fingolimod. Se recogen las características demográficas, clínicas y farmacológicas. Se describe la efectividad del fármaco -tasa anualizada de brotes (TAB) y porcentaje de pacientes libres de brotes- al año y a los dos años de tratamiento en relación con el año previo y datos de efectos secundarios. RESULTADOS: Se incluyó a 89 pacientes. El tratamiento previo fue inmunomodulador (interferón beta o acetato de glatiramero) en 54 pacientes y natalizumab en 32. Cincuenta pacientes cambiaron por fracaso con el inmunomodulador y 31 por serología positiva del virus JC (VJC+). La TAB global disminuyó el 67,3% el primer año (p < 0,0001) y el 84,1% el segundo (p = 0,0078). Disminuyó en los pacientes con fracaso del inmunomodulador (el 85,6% el primer año, p < 0,0001; el 88,9% el segundo año, p = 0,0039) y aumentó de forma no significativa en los pacientes VJC+ en el primer año. El porcentaje de pacientes libres de brotes en la población global aumentó del 32,6 al 68,1% en el primer año (p < 0,0019) y al 82,6% en el segundo (p = 0,0215). Este aumento no se observó en los pacientes VJC+. Trece pacientes tuvieron efectos secundarios, que obligaron a la retirada del fármaco en dos de ellos. CONCLUSIÓN: En la práctica clínica de la provincia de Alicante, el fingolimod mostró una efectividad y una seguridad ligeramente superiores a las de los ensayos clínicos

INTRODUCTION: Post-authorisation studies are important to confirm whether the outcomes of clinical trials are reproduced in usual clinical practice. AIMS: To evaluate the effectiveness and safety of fingolimod in clinical practice in the province of Alicante. PATIENTS AND METHODS: A retrospective multi-centre study was conducted with remitting multiple sclerosis patients treated with fingolimod. Demographic, clinical and pharmacological data were collected. We report on the effectiveness of the drug -annualised relapse rate (ARR) and percentage of patients free from attacks- at one and at two years after treatment in relation to the previous year, and data concerning side effects are also provided. RESULTS: The sample consisted of 89 PATIENTS: Previous treatment was with immunomodulators (interferon beta or glatiramer acetate) in 54 patients and natalizumab in 32. Fifty patients changed due to failure with the immunomodulator and 31 owing to positive serology for JC virus (JCV+). Overall ARR decreased by 67.3% the first year (p < 0.0001) and by 84.1% the second (p = 0.0078). It diminished in patients with immunomodulator failure (85.6% the first year, p < 0.0001; 88.9% the second year, p = 0.0039) and increased in a non-significant manner in JCV+ patients in the first year. The percentage of patients free from relapses in the overall population increased from 32.6% to 68.1% in the first year (p < 0.0019) and to 82.6% in the second (p = 0.0215). This increase was not observed in JCV+ PATIENTS: Side effects were reported by 13 patients, which led to the drug being withdrawn in two of them. CONCLUSIONS: In clinical practice in the province of Alicante, levels of effectiveness and safety of fingolimod proved to be slightly higher than those found in clinical trials (AU)