A short washout period from fingolimod to anti-CD20 therapy is safe and decreases the risk of reactivation.

The frequency of switches between Disease Modifying Therapies (DMTs) in Multiple Sclerosis (MS) has increased considerably over previous years. Between fingolimod and anti-CD20 therapies, a 1-month washout period is usually recommended. However, disease reactivations are frequent after fingolimod (Fg) cessation. Using a retrospective observational monocentric exposed/non-exposed cohort study, we investigated the efficacy and the safety of a shorter washout period (WP) between Fg and anti-CD20. We compared two groups: 25 patients with a short WP (<21 days) and 20 patients with a longer WP (>21 days). We observed no reactivation during WP in patients with a short WP against a relapse in 55% of patients in the longer group. Moreover, clinical and biological safety was excellent. Based on these findings, we recommend a shorter WP between fingolimod and anti-CD20 therapies in MS.

A randomized double-blind placebo-controlled trial of low-dose interleukin-2 in relapsing-remitting multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is associated with regulatory T cells (Tregs) insufficiency while low-dose interleukin-2 (IL2LD) activates Tregs and reduces disease activity in autoimmune diseases. METHODS: We aimed at addressing whether IL2LD improved Tregs from MS patients. MS-IL2 was a single-center double-blind phase-2 study. Thirty patients (mean [SD] age 36.8 years [8.3], 16 female) with relapsing-remitting MS with new MRI lesions within 6 months before inclusion were randomly assigned in a 1:1 ratio to placebo or IL-2 at 1 million IU, daily for 5 days and then fortnightly for 6 months. The primary endpoint was change in Tregs at day-5. RESULTS: Unlike previous trials of IL2LD in more than 20 different autoimmune diseases, Tregs were not expanded at day-5 in IL2LD group, but only at day-15 (median [IQR] fold change from baseline: 1.26 [1.21-1.33] in IL2LD group; 1.01 [0.95-1.05] in placebo group, p < 0.001). At day-5, however, Tregs had acquired an activated phenotype (fold change of CD25 expression in Tregs: 2.17 [1.70-3.55] in IL2LD versus 0.97 [0.86-1.28] in placebo group, p < 0.0001). Regulator/effector T cells ratio remained elevated throughout treatment period in the IL2LD group (p < 0.001). Number of new active brain lesions and of relapses tended to be reduced in IL2LD treated patients, but the difference did not reach significance in this trial not powered to detect clinical efficacy. CONCLUSION: The effect of IL2LD on Tregs in MS patients was modest and delayed, compared to other auto-immune diseases. This, together with findings that Tregs improve remyelination in MS models and recent reports of IL2LD efficacy in amyotrophic lateral sclerosis, warrants larger studies of IL2LD in MS, notably with increased dosages and/or modified modalities of administration. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov: NCT02424396; EU Clinical trials Register: 2014-000088-42.

Genetics and familial distribution of multiple sclerosis: A review.

PURPOSE OF REVIEW: This article reviews the genetics of multiple sclerosis (MS), as well as intra-familial concordance and clinical correlations between different members of a family. Indeed, significant findings have been made on these topics in recent years. RECENT FINDINGS: The influence of specific genes on the clinical or radiological presentation of MS has been described as well as preliminary findings in the field of pharmacogenomics. Within familial forms of MS, correlations on specific aspects of the disease have been described, such as the age of onset or the clinical course between siblings. SUMMARY: The genetic contribution to the risk of developing MS is now estimated to be about 50%, with the genes involved mainly located within the major histocompatibility complex. Familial MS represents 12.6% of all MS cases, with the risk depending on the degree of genetic proximity to the index case. Furthermore, these familial cases seem to have a different clinical presentation from sporadic cases such as earlier worsening of disability and more severe long-term disability. Clinical correlations between different members of a family with MS have also been described, such as a similar age of onset between siblings, but deep clinical and radiological phenotyping is warranted to investigate MS disease severity concordance within familial cases of MS.

Patient needs and preferences in relapsing-remitting multiple sclerosis: A systematic review.

BACKGROUND: Considering the multiple treatments approved for multiple sclerosis (MS) by the Food and Drug Administration (FDA) and European Medicines Agency (EMA), determining a treatment strategy for patients with clinically isolated syndrome (CIS) and relapsing-remitting MS (RRMS) can be challenging. To date, an overview of the needs and preferences of patients at each treatment decision-making moment is lacking. Therefore, the aim of this systematic review is to examine the existing literature about the needs and preferences of patients with CIS and RRMS when making treatment decisions. METHODS: A systematic search was done using Embase, Medline, PsychINFO, Web of Science and Google Scholar. Eligibility criteria included whether the article described a study of adults with CIS/RRMS and reported patient needs or preferences regarding first-line disease modifying treatment (DMT) decisions. Publications were categorized by treatment decision: initiation of first DMT (D1), DMT adherence/discontinuation (D2a/D2b), and switch to a second DMT (D3). A separate category was created for stated preference studies such as discrete choice experiment methods to examine the relative importance of different treatment attributes. Publications were compared to identify key factors. RESULTS: The search yielded 2789 articles after removal of duplicates and 434 full-text publications were reviewed for eligibility. Twenty-four articles fulfilled all criteria: n = 5 (D1), n = 12 (D2a), n = 13 (D2b), and n = 3 (D3); six articles studied more than one treatment decision. The need for social support is important during D1. The most commonly reported reasons for adherence/discontinuation/switch included forgetfulness, side-effects, and injection-related reasons. Eight articles described preference studies; the most important DMT attributes were efficacy, mode and frequency of administration, and side-effect profile. CONCLUSIONS: Understanding the needs and preferences of CIS/RRMS patients regarding DMT attributes and non-treatment related attributes are important to improve treatment decision-making and reduce non-adherence. Studies are needed to understand patient preferences upon treatment initiation. Furthermore, preference studies should include attributes based on the patient perspective.

MSCopilot, a new multiple sclerosis self-assessment digital solution: results of a comparative study versus standard tests.

BACKGROUND AND PURPOSE: Assessing patients' disability in multiple sclerosis (MS) requires time-consuming batteries of hospital tests. MSCopilot is a software medical device for the self-assessment of patients with MS (PwMS), combining four tests: walking, dexterity, cognition and low contrast vision. The objective was to validate MSCopilot versus the Multiple Sclerosis Functional Composite (MSFC). METHODS: This multicentre, open-label, randomized, controlled, crossover study enrolled 141 PwMS and 76 healthy controls (HCs). All participants performed MSCopilot and MSFC tests at day 0. To assess reproducibility, 46 PwMS performed the same tests at day 30 ± 3. The primary end-point was the validation of MSCopilot versus MSFC for the identification of PwMS against HCs, quantified using the area under the curve (AUC). The main secondary end-point was the correlation of MSCopilot z-scores with MSFC z-scores. RESULTS: In all, 116 PwMS and 69 HCs were analysed. The primary end-point was achieved: MSCopilot performance was non-inferior to that of MSFC (AUC 0.92 and 0.89 respectively; P = 0.3). MSCopilot and MSFC discriminated PwMS and HCs with 81% and 76% sensitivity and 82% and 88% specificity respectively. Digital and standard test scores were highly correlated (r = 0.81; P < 0.001). The test-retest study demonstrated the good reproducibility of MSCopilot. CONCLUSION: This study confirms the reliability of MSCopilot and its usability in clinical practice for the monitoring of MS-related disability.

Impact of an adaptive program for cognitive and emotional deficits (ADACOG program) in multiple sclerosis patients with cognitive impairments.

BACKGROUND: Cognitive impairment is frequent in multiple sclerosis (MS), affecting approximately 40 to 70% of patients. We developed a psycho-educational program (ADACOG program) to allow patients to cope with cognitive deficits. The purpose of this exploratory study was to investigate the impact of the ADACOG program on subjective self-reported cognitive impairments, quality of life, anxiety, depression and self-esteem in MS patients. METHODS: ADACOG program is a psycho-educational program focusing on cognitive and emotional dysfunctions in MS consisting of three modules in small groups lasting two hours every two weeks. Forty-five MS patients with self-reported cognitive impairments and objective cognitive deficits were enrolled consecutively in two groups: (i) the ADACOG group (N=24) and (ii) the control group (N=21). Both groups of patients completed questionnaires evaluating self-reported cognitive impairments (Multiple Sclerosis Neuropsychological Screening Questionnaire), quality of life (Multiple Sclerosis Impact Scale), anxiety and depression (Hospital Anxiety and Depression Scale, HAD) and self-esteem (Rosenberg Scale) at inclusion (M0), one month later (M1) and seven months after inclusion (M7). The evolution of outcomes within ADACOG group and between both groups was analyzed. RESULTS: The analyses within the ADACOG group showed that patients reported better quality of life and fewer anxiety symptoms at M1 compared to M0 (respectively P=0.03 and P=0,04). Moreover, patients presented less subjective self-reported cognitive deficits at M7 compared to M0 (P=0.003). Score evolution for HAD depression and self-esteem were not significant within the ADACOG group. The change M1-M0 for MSIS-29 and HAD anxiety scores was significantly different between both groups (respectively P=0.04 and P=0.008), with improvement of quality of life and anxiety in the ADACOG group. The evolution of scores between groups was not significant for the other outcomes. DISCUSSION: This study showed a small effect of a psycho-educational program focusing on cognitive and emotional disorders in MS patients with subjective self-reported cognitive deficits and objective cognitive deficits. Interest of psycho-education focusing on cognition in MS patients is discussed.

Conventional and advanced MRI in multiple sclerosis.

Magnetic resonance imaging (MRI) plays a central role in the management of patients with multiple sclerosis (MS). T2-weighted/FLAIR lesions have been included in the diagnostic criteria since 2001, and the importance of the technology has been expanded in each successive revision of the McDonald criteria. While the typical focal hyperintense lesions seen on T2 and FLAIR sequences in several areas of the central nervous system are key features for MS diagnosis, they can also be used to monitor disease activity, particularly in asymptomatic patients, and to evaluate therapeutic responses. The development of new lesions, particularly in medullary and infratentorial locations, is a strong predictor of long-term disability and risk of evolution to a secondary-progressive phase. Yet, changes in T2 lesion volume are poor predictors of subsequent disease evolution in many cases, a situation often referred to as the "clinicoradiological paradox". Nevertheless, advanced MRI techniques allow quantification of several pathological processes in vivo and offer insights into MS pathophysiology beyond white matter lesions. By investigating what is happening beneath the visible surface of MS pathology, these techniques not only help to unravel the clinicoradiological paradox, but also provide early measures of functional and structural tissue abnormalities before the advent of irreversible neurodegeneration.