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.

Updated Perspectives on the Challenges of Managing Multiple Sclerosis During Pregnancy.

Multiple sclerosis (MS) is a chronic immune-mediated, inflammatory, and degenerative disease that is up to three times more frequent in young women. MS does not alter fertility and has no impact on fetal development, the course of pregnancy, or childbirth. The Pregnancy in Multiple Sclerosis Study in 1998 showed that pregnancy, mostly in untreated women, did not adversely affect MS, as disease activity decreased during pregnancy (although it significantly increased in the first trimester postpartum). These findings, together with the limited information available on the potential risks of fetal exposure to disease modifying treatments (DMTs), meant that women were advised to delay the onset of DMTs, stop them prior to conception, or, in case of unplanned pregnancy, discontinue them when pregnancy was confirmed. Now, many women with MS receive DMTs before pregnancy and, despite being considered a period of MS stability, up to 30% of patients could relapse in the first trimester postpartum. Factors associated with an increased risk of relapse and disability during pregnancy and postpartum include relapses before and during pregnancy, a greater disability at the time of conception, the occurrence of relapses after DMT cessation before conception, and the use of high-efficacy DMTs before conception, especially natalizumab or fingolimod. Strategies to prevent postpartum activity are needed in some patients, but consensus is lacking regarding the therapeutic strategies for women with MS of a fertile age. This, along with the increasing number of DMTs, means that the decision-making processes in aspects related to family planning and therapeutic strategies before, during, and after pregnancy are increasingly more complex. The purpose of this review is to provide an update on pregnancy-related issues in women with MS, including recommendations for counseling, general management, use of DMTs in pre-pregnancy, pregnancy, and postpartum periods, and breastfeeding-related aspects of DMTs.

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.

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.

Observational Study of Switching from Natalizumab to Immunomodulatory Drugs.

OBJECTIVE: To determine the effect of disease-modifying drugs (DMDs) on disease activity rebound in patients discontinuing natalizumab (NTZ). METHODS: Twenty-one patients with relapsing-remitting multiple sclerosis (RRMS) treated with NTZ for ≥1 year and who switched to DMDs (glatiramer acetate [GA] or interferon) were followed up for 12 months in clinical practice. Clinical outcomes after NTZ cessation were assessed every 3 months for 1 year and MRI was performed at 12 months. RESULTS: Twelve months after switching from NTZ to DMDs, there were no significant differences in the annualized relapse rate (ARR) compared to the days that NTZ was used (0.3 vs. 0.1; p = 0.083); and the ARR never reached similar values to those prior to NTZ use (1.61; p < 0.001). The percentage of relapse-free patients after switching from NTZ was 71.4%. These patients did not have lower disease activity before NTZ compared with those with clinical relapses (1.3 vs. 1.7; p = 0.302), but they had lower Expanded Disability Status Scale scores (3.4 vs. 5.7; p = 0.001). DMDs had beneficial effects on MRI parameters, as 10 of 16 patients (62.5%) presented no evidence of radiological activity 12 months after NTZ discontinuation. CONCLUSIONS: Patients with RRMS and moderate disability who discontinued NTZ for safety reasons may benefit from the DMDs GA and interferon with no known risk for progressive multifocal leukoencephalopathy.

Prevalence of multiple sclerosis in Health District III, Murcia, Spain.

BACKGROUND: The prevalence of multiple sclerosis (MS) varies throughout the world, and available epidemiological data suggest a progressively increasing prevalence of MS in Spain. The objective of this study was to calculate MS prevalence in Health District III of the autonomous community of Murcia in Spain. METHODS: This is an observational, cross-sectional, descriptive study. The prevalence of MS in Health District III in the Region of Murcia, which includes the municipalities of Lorca, Totana, Águilas, Puerto Lumbreras and Aledo, was calculated from the total population (171,040 inhabitants), and among native Spanish citizens only (137,659 persons). Healthcare and demographic data were obtained from three sources: 1) OMI-AP: the local primary care computer system containing the medical records of all subscribers; 2) the medical record database of the Hospital Rafael Mendez (the single hospital in the district); and 3) the records of the AEMA III Multiple Sclerosis Association to which patients from this healthcare district belong. Data from these three sources were combined to check the accuracy and completeness of the patient records. RESULTS: The prevalence of MS among the general population of this district, including non-Spanish individuals, was 71.9 per 100,000 inhabitants (95% CI=60-85). Prevalence among the native Spanish population was 82.0 per 100,000 (95% CI=68-98). Considering prevalence by sex, it was 118.1 per 100,000 (95% CI: 95-146) in the female native Spanish population, and 45.4 per 100,000 (95% CI: 31-64) in the male native Spanish population. The prevalence in the native Spanish population in this district was calculated by sex and age (grouped by decades). A peak was observed among women aged between 20 and 29 years: 234.2 per 100,000 inhabitants (95% CI: 151-361). CONCLUSION: Our results suggest that the population in this healthcare district presents a risk of MS similar to that recently reported in other regions of Spain, which is higher than in previous decades.

Cirugía bariátrica en pacientes con esclerosis múltiple: ¿un mayor riesgo? / Bariatric surgery in patients with multiple sclerosis

Background: There is limited information about the role of bariatric surgery among patients with motor deficits. Case reports: We report a 38 years old woman with a body mass index (BMI) of 49 kg/m² and a 34 years old woman with a BMI of 40 kg/m², both with multiple sclerosis, subjected to a laparoscopic gastric bypass. Both were unable to lose weight with medical management. No postoperative complication was recorded, both patients lost weight and their quality of life improved.

Introducción: Hay escasa literatura acerca del papel de la cirugía bariátrica en el manejo de las enfermedades neurológicas con déficit motor. Este déficit motor supone una desventaja sobreañadida si además los pacientes son obesos mórbidos. Casos clínicos: Presentamos dos casos de obesidad mórbida y esclerosis múltiple intervenidas de by pass gástrico laparoscópico. El primer caso es una mujer de 38 años con IMC de 49 y el segundo es una mujer de 34 años con IMC de 40. Tras varios intentos fallidos de pérdida de peso e ingresos programados para dieta absoluta son remitidas por los servicios de Endocrinología y neurología para valorar cirugía bariátrica para pérdida de peso y facilitar la dosificación de tratamiento especifico. No se produjo ninguna complicación postquirúrgica inmediata. La pérdida de peso fue favorable al año de seguimiento, mejorando la calidad de vida de estas pacientes.