Effects of MS disease-modifying therapies on responses to vaccinations: A review.

BACKGROUND: Development of long-term immunologic memory relies upon humoral and cellular immune responses. Vaccinations aim to stimulate these responses against pathogens. Several studies have evaluated the impact of multiple sclerosis disease-modifying therapies on immune response to vaccines. Findings from these studies have important implications for people with multiple sclerosis who require vaccination and are using disease-modifying therapies. METHODS: Searches using PubMed and other engines were conducted in May 2020 to collect studies evaluating the impact of various disease-modifying therapies on immune responses to vaccination. RESULTS: Several studies demonstrated preserved immune responses in people treated with beta-interferons to multiple vaccine types. Limited data suggest vaccine responses to be preserved with dimethyl fumarate treatment, as well. Vaccine responses were reduced to varying degrees in those treated with glatiramer acetate, teriflunomide, sphingosine-1-phosphate receptor modulators, and natalizumab. The timing of vaccination played an important role in those treated with alemtuzumab. Humoral vaccine responses were significantly impaired by B cell depleting anti-CD20 monoclonal antibody therapies, particularly to a neoantigen. Data are lacking on vaccine responses in patients with multiple sclerosis taking cladribine and high-dose corticosteroids. Notably, the majority of these studies have focused on humoral responses, with few examining cellular immune responses to vaccination. CONCLUSIONS: Prior investigations into the effects of individual disease-modifying therapies on immune responses to existing vaccines can serve as a guide to expected responses to a SARS-CoV-2 vaccine. Responses to any vaccination depend on the vaccine type, the type of response (recall versus response to a novel antigen), and the impact of the individual disease-modifying therapy on humoral and cellular immunity in response to that vaccine type. When considering a given therapy, clinicians should weigh its efficacy against MS for the individual patient versus potential impact on responses to vaccinations that may be needed in the future.

Clinical instrument to retrospectively capture levels of EDSS.

BACKGROUND: The Expanded Disability Status Scale (EDSS), a common outcome measure in Multiple Sclerosis (MS), is obtained prospectively through a direct standardized evaluation. The objective of this study is to develop and validate an algorithm to derive EDSS scores from previous neurological clinical documentation. METHODS: The algorithm utilizes data from the history, review of systems, and physical exam. EDSS scores formally obtained from research patients were compared to captured EDSS (c-EDSS) scores. To test inter-rater reliability, a second investigator captured scores from a subset of patients. Agreement between formal and c-EDSS scores was assessed using a weighted kappa. Clinical concordance was defined as a difference of one-step in EDSS (0.5) and functional system (1.0) scores. RESULTS: Clinical documentation from 92 patients (EDSS range 0.0-8.5) was assessed. Substantial agreement between the c-EDSS and formal EDSS (kappa 0.80; 95% CI 0.74-0.86) was observed. The mean difference between scores was 0.16. The clinical concordance was 78%. Near-perfect agreement was found between the two raters (kappa 0.89; 95% CI 0.84-0.95). The mean inter-rater difference in c-EDSS was 0.23. CONCLUSIONS: This algorithm reliably captures EDSS scores retrospectively with substantial correlation with formal EDSS and high inter-rater agreement. This algorithm may have practical implications in clinic, MS research and clinical trials.

Disease-Modifying Treatment in Progressive Multiple Sclerosis.

PURPOSE OF REVIEW: Multiple sclerosis (MS) is an immune-mediated disorder that affects the central nervous system (CNS), often first affecting people in early adulthood. Although most MS patients have a relapsing-remitting course (RRMS) at disease onset, a substantial proportion later develop chronic progression, termed secondary progressive MS (SPMS). Approximately 10% of MS patients experience chronic progression from disease onset, termed primary progressive multiple sclerosis (PPMS). Although several disease-modifying treatment (DMT) options exist for relapsing forms of this disease, DMT options are few for progressive MS (PPMS and SPMS). Herein, we strive to define progressive MS, review major clinical trials aimed at progressive MS, and delineate potential strategies in the management of progressive MS. RECENT FINDINGS: In 2017, the first DMT for PPMS, the B lymphocyte-depleting monoclonal antibody, ocrelizumab, came to market. Ocrelizumab reduced 12-week confirmed disability progression (CDP) by 24% versus placebo. Siponimod, a selective sphingosine-1-phosphate receptor modulator, reduced 3-month CDP by 21% versus placebo in SPMS. Ibudilast slowed brain atrophy in PPMS and SPMS patients in a multicenter phase 2b study. Smaller early phase studies of alpha-lipoic acid and simvastatin each found slowing of rate of whole brain atrophy in SPMS patients. Reasons now exist for optimism in the search for DMTs for progressive MS. It remains a challenge to identify outcome measures that accurately reflect the underlying pathology in progressive MS, which is less inflammatory and more degenerative than RRMS.