The continuous improvements of our understanding of the pathophysiological changes that occur in multiple sclerosis (MS) have translated into many novel therapeutic agents at different stages of development. These agents target more specifically the innate or the adaptive immune response. We will review agents available or under development that target the humoral pathways of the adaptive immune response. As such, humoral targeted immunotherapies that are being developed for MS are discussed herein: rituximab, ocrelizumab, and ofatumumab show promise as B-cell depleting agents. Other agents, such as atacicept were suspended during development in MS due to increased inflammatory activity versus the placebo. Although most agents were tested in relapsing-remitting forms of MS, rituximab and ocrelizumab have both been studied in progressive MS, whereas ocrelizumab only is currently moving forward in primary progressive MS trials. We provide an overview of agents available and under development that target the humoral response and include their mechanisms of action, safety profiles, and results of clinical trials.

Background

Transitioning youth with multiple sclerosis (MS) represent a vulnerable group to potentially poor outcomes. It is unknown how pediatric MS patients transition into adult care.

Objectives

To describe self-management skills that include adherence to disease-modifying therapies, quality of life measures, illness perception, transition readiness and healthcare skills assessments in patients with pediatric MS and associations with clinical and cognitive outcomes.

Methods

This is a prospective cross-sectional study at the pediatric MS center and transitional MS clinic at the University of California, San Francisco. Patients and one of their parents completed validated surveys for self-management skills. Non-adherence is defined as not taking their medication more than 20% of the time in the past 1 month. Wilcoxin matched-pairs rank test and McNemar's tests were used for comparison of patient and parent responses. Univariate and multivariate regression models were used for analyses adjusting for disease duration and socio-economic status.

Results

Thirty patients were enrolled with a mean (+/-SD) age of 15.8 years+/-2.8, 53% was female and 47% Hispanic. The rate of non-adherence was 37%. The most common reason for non-adherence was forgetting to take their medication reported in 50% of patients. In adjusted regression models, higher EDSS was associated with a lower score on patient's quality of life (13 points decrease, 95% CI 6–18, p<0.0001), and lower healthcare skills (15 points decrease, 95% CI5–26, p=0.006). Four points increase in Symbol Digit Modalities Test score was associated a 0.1 increase in transition readiness score (95% CI0.07–0.2, p=0.001) and 3.9 points increase in health care skills scores (95% CI 1.7–6, p=0.008).

Background

High salt intake may be associated with pro-inflammatory changes in the immune response, and increased clinical and MRI activity in adults with relapsing-remitting multiple sclerosis.

Objective

We sought to determine if dietary salt intake is associated with pediatric-onset MS risk in a multicenter, case-control study.

Methods

Pediatric-onset CIS/MS cases within four years of onset and controls less than 22 years old recruited from 14 pediatric-MS centers were studied. Dietary sodium intake was assessed using the validated Block Kids Food Screener (NutritionQuest). Sodium intake, excess sodium, and sodium terciles were compared between cases and controls. Logistic regression models were adjusted for age, gender, ethnicity, body mass index, and socioeconomic status.

Results

Among 170 cases (mean age=15.2±3.5) and 331 controls (mean age=14.0±3.7), no significant difference in unadjusted mean sodium intake was found between cases (2044mg/d) and controls (2030mg/d, p=0.99). The proportion of subjects consuming excess sodium, based on the adequate intake for age and gender, was similar between cases and controls (65% versus 69%, p=0.34). There were no increased odds of higher sodium intake among cases as compared to controls (for each 100mg/d increase in sodium, OR=1.00, 95% CI 0.98, 1.02; p=0.93, for excess sodium intake, OR=1.05, 95% CI 0.67, 1.64; p=0.84).

Conclusions

Our results show no strong association between dietary salt intake and pediatric-onset MS risk, suggesting that salt intake may not play a prominent role in susceptibility to MS in children.