Effectiveness and Safety of Teriflunomide in Relapsing-Remitting Multiple Sclerosis and Improvements in Quality of Life: Results from the Real-World TERICARE Study.

INTRODUCTION: Teriflunomide is a once-daily oral immunomodulator approved for relapsing forms of multiple sclerosis (MS) or relapsing-remitting multiple sclerosis (RRMS; depending on the local label), based on extensive evidence from clinical trials and a real-world setting on efficacy, tolerability and patient-reported benefits. The TERICARE study assessed the impact of teriflunomide treatment over 2 years on health-related quality of life (HRQoL) and some of the most common and disabling symptoms of MS, such as fatigue and depression. METHODS: This prospective observational study in Spain included RRMS patients treated with teriflunomide for ≤ 4 weeks. The following patient-reported outcomes (PROs) were collected at baseline and every 6 months for 2 years: the 29-item Multiple Sclerosis Impact Scale version 2 (MSIS-29), the 21-item Modified Fatigue Impact Scale (MFIS-21), the Beck Depression Inventory (BDI-II), the Short Form (SF)-Qualiveen and the Treatment Satisfaction Questionnaire for Medication v1.4 (TSQM). Annualised relapse rate (ARR), disability progression according to the Expanded Disability Status Scale (EDSS), and no evidence of disease activity (NEDA-3) were also assessed. RESULTS: A total of 325 patients were analysed. Patients had a mean (SD) age of 43.2 years (10.4), a mean baseline EDSS score of 1.75 (1.5), a mean number of relapses in the past 2 years of 1.5 (0.7), and 64% had received prior disease-modifying therapy (DMT). Patients showed significant improvements in the psychological domain of MSIS-29 from 35.9 (26.6) at baseline to 29.4 (25.5) at 18 months (p = 0.004) and 29.0 (24.6) at 24 months (p = 0.002). Levels of fatigue and depression were also reduced. After 2 years of treatment with teriflunomide, ARR was reduced to 0.17 (95% CI 0.14-0.21) from the baseline of 0.42 (95% CI 0.38-0.48), representing a 60.1% reduction. Mean EDSS scores remained stable during the study, and 79.9% of patients showed no disability progression. 54.7% of patients achieved NEDA-3 in the first 12 months, which increased to 61.4% during months 12-24. Patients reported increased satisfaction with treatment over the course of the study, regardless of whether they were DMT naive or not. CONCLUSION: Teriflunomide improves psychological aspects of HRQoL and maintains low levels of fatigue and depression. Treatment with teriflunomide over 2 years is effective in reducing ARR and disability progression.

Discontinuation of disease-modifying treatments in multiple sclerosis to plan a pregnancy: A retrospective registry study.

BACKGROUND: For safety reasons multiple sclerosis (MS) treatment guidelines recommend stopping or delaying the onset of disease-modifying therapies (DMT) before a planned pregnancy, but disease stability after DMT discontinuation is not well studied. The objective of this study is to describe the course of MS in patients who interrupted DMT before a planned pregnancy. METHODS: This was a retrospective study using 2008-2016 data from a multicenter register of pregnancies in women with MS. In this paper, we present data from the subgroup of women with relapsing-remitting MS (RRMS) who interrupted DMT to try to conceive. Data from 1 and 3 years before DMT interruption, the period between DMT interruption and conception or resuming DMT, during pregnancy and one year postpartum were analyzed. Annualized relapse rates (ARR), Expanded Disability Status Scale (EDSS) scores, and magnetic resonance imaging (MRI), obstetric, and neonatal data were collected. RESULTS: Twenty-seven women interrupted DMT (19 ß-interferon, 5 glatiramer acetate, 2 natalizumab and 1 fingolimod) to try to conceive. After a mean of 10.6 months 6 women stopped trying to conceive and resumed DMT, while 21 women became pregnant after a mean of 7.0 months. In the overall cohort, in the period from when DMT was discontinued to when pregnancy was confirmed or DMT resumed, the ARR was 1.08, which was significantly higher than the ARR 1 year (0.44; p = 0.01) and 3 years (0.4; p = 0.06) before DMT discontinuation. The mean EDSS score when pregnancy was confirmed or DMT resumed was significantly higher than at DMT discontinuation (1.8 vs 1.36, p = 0.011). In the subgroup of patients who became pregnant, the ARR in the untreated period before pregnancy was 0.98, which was significantly higher than the ARR 1 year (0.38; p = 0.03) and 3 years (0.39; p = 0.0077) before DMT discontinuation. The ARR decreased to 0.51 during pregnancy and then increased to 0.76 during the first postpartum trimester (not significant). One year after delivery, the mean EDSS score (1.86) was significantly higher than at DMT cessation (1.35, p = 0.027) or pregnancy confirmation (1.45, p = 0.026). Patients who suffered relapses following DMT cessation before becoming pregnant had an 11-fold higher risk of relapse during pregnancy (relative risk [RR] = 11.1 [95%CI 1.6, 75], p = 0.002) and a 3-fold higher risk during the postpartum year (RR = 3.0 [95%CI 1.3,6.6], p = 0.007) than those who did not suffer relapses in period between DMT withdrawal and pregnancy. CONCLUSIONS: In this retrospective registry study, discontinuation of DMT (mostly immunomodulatory drugs), to try to conceive resulted in an increase in MS relapse rates and disability progression.

Episodic migraine and chest pain as the first manifestation of small cell lung carcinoma.

Migraine-like associated with chest pain is an alarming association and forces us to rule out the presence of a secondary cause. That must be taken into account in the differential diagnosis of craniofacial hemicranial pain that appears in patients with no personal history of headache, and risk factors for the development of pulmonary neoplasia.

Spanish real-world experience with fingolimod in relapsing-remitting multiple sclerosis patients: MS NEXT study.

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.

Efectividad y seguridad del fingolimod en la práctica clínica habitual en pacientes con esclerosis múltiple remitente recurrente en España: análisis intermedio del estudio MS NEXT / Efficacy and safety of fingolimod in routine clinical practice in patients with relapsing-remitting multiple sclerosis in Spain: an intermediate analysis of the MS NEXT study

Introducción. El fingolimod es un tratamiento modificador de la enfermedad que ha demostrado eficacia y seguridad en ensayos clínicos en pacientes con esclerosis múltiple remitente recurrente (EMRR). Objetivo. Evaluar la efectividad y la seguridad del fingolimod en pacientes con EMRR en la práctica clínica. Pacientes y métodos. Se presentan los resultados del análisis intermedio (julio de 2015) del MS NEXT, un estudio observacional, multicéntrico y retrospectivo. Se incluyó a 442 pacientes (edad media: 41 ± 9 años; escala expandida del estado de discapacidad basal, mediana: 3; 70% mujeres; 284 previamente tratados con tratamientos modificadores de la enfermedad de primera línea, 139 con natalizumab y 19 naïve; media de tratamiento con fingolimod: 25 ± 9 meses) tratados con fingolimod a partir de noviembre de 2011 y con al menos 12 meses de seguimiento. Participaron 56 hospitales españoles. Se recogieron datos demográficos y clínicos (basal y anualmente, número de brotes, puntuación en la escala expandida del estado de discapacidad y actividad radiológica). También se registraron los efectos adversos durante el seguimiento. Resultados. Tras dos años de tratamiento, la tasa anualizada de brotes se redujo un 76%; el 67% de los pacientes estaba libre de brotes; el 91%, libre de progresión de la discapacidad confirmada a los tres meses; el 63%, libre de brotes y progresión de discapacidad; el 50%, libre de actividad radiológica, y el 35%, libre de brotes, progresión de discapacidad y actividad radiológica. Un 3,9% abandonó el fingolimod permanentemente. Conclusiones. En este análisis intermedio, la mayoría de los pacientes tratados con fingolimod en la práctica clínica presenta una actividad clínica controlada y una elevada persistencia al tratamiento

Introduction. Fingolimod is a disease modifying therapies, which has showed clinical efficacy and an acceptable safety profile in clinical trials with relapsing-remitting multiple sclerosis (RRMS) patients. Aim. To assess fingolimod effectiveness and safety in patients with RRMS in clinical practice. Patients and methods. We present an interim analysis (July 2015) of MS NEXT, an observational, retrospective and multicenter study. 442 patients were included (mean age: 41 +/- 9 years; median baseline EDSS: 3.0; 70% female; 284 previously treated with first-line disease modifying therapies, 139 with natalizumab and 19 without a previous treatment; mean fingolimod treatment duration: 25 ± 9 months) treated with fingolimod from November 2011 and with at least 12 months follow-up. 56 neurology-unit Spanish hospitals enrolled patients. Basal clinical and demographic data were recorded. Relapses, EDSS scores and radiological activity were recorded at baseline and annually. Adverse events were also recorded during the follow-up period. Results. After two years of follow-up: annual relapse rates decreased by 76%, the proportion of relapse-free patients was 67%, of disability progression-free patients confirmed at 3 months was 91%, of relapse and disability progression-free patients was 63%, of radiological activity-free patients was 50%, and the proportion of relapse, disability progression and radiological activity-free patients was 35%. Only 3.9% of patients discontinued fingolimod permanently during the first year of treatment. Conclusions. In this interim analysis, most of patients treated with fingolimod in clinical practice had a controlled clinical disease activity, stable disability progression and high persistency

Progressive Demyelination in the Presence of Serum Myelin Oligodendrocyte Glycoprotein-IgG: A Case Report.

The clinical diagnosis of patients with autoantibodies directed to conformational myelin oligodendrocyte glycoprotein MOG-IgG, can be challenging because of atypical clinical presentation. MOG-IgG seropositivity has been reported in several demyelinating diseases, including relapsing opticospinal syndromes [in the neuromyelitis optica spectrum disorders (NMOSD) and less frequently, in multiple sclerosis (MS)], but it has rarely been associated with the progressive course of disease. To contribute to the characterization of MOG-related demyelination, we describe the case of a patient with progressive demyelinating opticospinal disease, IgG-oligoclonal bands (OCB), and serum MOG-IgG.

Effect of tetrahydrocannabinol:cannabidiol oromucosal spray on activities of daily living in multiple sclerosis patients with resistant spasticity: a retrospective, observational study.

AIM: To examine evolution in activities of daily living (ADL) in patients with multiple sclerosis spasticity during long-term use of tetrahydrocannabinol (THC):cannabidiol (CBD) oromucosal spray. METHODS: Functional impairment was assessed retrospectively (prior to start of treatment) and at the present moment using a 16-item ADL survey; results were compared. A control group without add-on THC:CBD oromucosal spray was included to investigate possible recall bias. RESULTS: ADL was maintained or slightly improved with THC:CBD oromucosal spray across treatment time (mean 31.9 months) including significant improvement in 'standing up' (p < 0.05) and trends in other items. Significant improvements (p < 0.01) with THC:CBD oromucosal spray were observed in several multiple sclerosis spasticity-related symptoms. Overall, 96.9% of patients using THC:CBD oromucosal spray had a positive global impression of change during treatment. CONCLUSION: In this pilot study, THC:CBD oromucosal spray maintained or improved aspects of daily functioning. Further study in a larger trial is warranted.

Predictors of burden and depression among caregivers of relapsing-remitting MS patients in Spain: MS Feeling study.

AIM: To assess potential predictors for burden and depression among caregivers of relapsing-remitting multiple sclerosis patients in Spain. Family functioning and social support were also assessed. PATIENTS & METHODS: Multicenter and cross-sectional study in relapsing-remitting multiple sclerosis adult patients and their respective informal caregivers (n = 180). Assessment performed: Zarit Scale (Burden), Center for Epidemiologic Studies Depression-7 Scale (depression), Family APGAR (Adaptation, Partnership, Growth, Affection, Resolve) Questionnaire (family functioning) and Duke UNC-11 Functional Social Support Questionnaire (social support). Multivariate logistic regression analysis assessed burden and depression predictors among caregivers. RESULTS: Caregivers suffered burden (19.4%) and depression (20.6%) and perceived poor social support (9.4%) and family dysfunction (10.6%). Burden predictors were patient's degree of disability, caregiver time and number of medications administered to patient. Depression predictors were patient's age and daily caregiving time. CONCLUSION: The factors reported here could help clinicians to identify caregiver groups particularly at risk of burden and depression for timely intervention.