Predictive factors and early biomarkers of response in multiple sclerosis patients treated with natalizumab

Abstract

there are an increasing number of treatments available for multiple sclerosis (MS). the early identification of optimal responders to individual treatments is important to achieve individualized therapy. With this aim, we performed a multicenter retrospective longitudinal study including 186 MS patients treated with natalizumab who were followed for 2 years. We analyzed the following variables at recruitment: sex, current age, age at disease onset, disease duration, EDSS, number of T2 and Gd + lesions, IgG and IgM oligoclonal bands, HLA class II (DR, DRB, DQA, DQB, and DRB1*15:01), IgG and IgM antibody titers against human herpesvirus 6 (HHV-6) and the antibody response to Epstein-Barr virus (EBV) through the measurement of the anti-EBNA-1 and anti-VCA IgG titers, in relation to clinical response (no relapses or disability progression), and to NEDA-3 (no evidence of disease activity in terms of clinical response and no changes in MRI scans either) after 2-years follow-up. Baseline EDSS score, baseline EBNA-1 IgG titers and percentage change of HHV6 IgG titers between baseline and 6 month visits were significantly different in clinical responders and in NEDA-3 status (all of them remained significant in the multivariate analysis). We identified three variables for the early identification of natalizumab optimal responders in a rapid and cost-effective approach. In the last years, there are an increasing number of treatments available for multiple sclerosis (MS) patients. Since natalizumab, a humanized monoclonal antibody against the cell adhesion molecule α4-integrin 1 , was approved by the U.S. Food and Drug Administration (FDA) in 2004 to treat MS, several treatments or new formulations have also been approved to treat this disease: fingolimod, teriflunomide, alemtuzumab, dimethyl fumarate, pegilated interferon beta-1a, ocrelizumab and cladribine 2. Therefore, to identify in an early stage the most appropriated treatment is of great importance to avoid treatment failures that could negatively affect the

Herpesvirus Antibodies, Vitamin D and Short-Chain Fatty Acids: Their Correlation with Cell Subsets in Multiple Sclerosis Patients and Healthy Controls

“…In this study, as we can see, in Supplementary Figure S1 , that HHV-6A/B IgG titers were not statistically significantly different between SPMS patients and HC, while the p -value was even more significant when we compared RRMS patients and HC ( p = 0.0008) than when we compared the whole population of MS patients with the HC ( p = 0.003). This is a cross-sectional study and we have not analyzed the relation between the evolution of the HHV-6A/B IgG titers and the progression of the disease in each patient, as we have done in other longitudinal studies [ 3 , 59 ]. Finally, since a paper analyzing HHV-6A and HHV-6B in MS patients has been recently published using a novel multiplex serological assay, it would be very interesting for future studies to know if the observed negative correlation between IgG titers and MSSS in treated MS patients is due to one of these two viruses or not [ 56 ].…”

Efficacy and safety of ocrelizumab in patients with relapsing‐remitting multiple sclerosis with suboptimal response to prior disease‐modifying therapies: A primary analysis from the phase 3b CASTING single‐arm, open‐label trial

“…This may be related to the fact that women had slightly higher baseline inflammatory MRI activity. Other studies have shown that the risk of not achieving NEDA was associated with clinical and MRI measures of disease activity and progression (e.g., higher baseline EDSS score, number of relapses in the previous 12 months, number of CELs) [ 33 , 34 , 35 ]. Conversely, studies of the prognostic value of NEDA status over 2 years in predicting future disability progression up to 10 years have provided conflicting data, but this was related to the DMT used, with few patients maintaining NEDA over the long term in studies in which self‐injectable DMTs were used, while NEDA was enhanced in patients over the long term in studies utilizing more effective DMTs [ 31 ].…”

Potential Biomarkers Associated with Multiple Sclerosis Pathology

“…In a more recent work, Dominguez-Mozo et al described that higher titer of IgG HHV-6 antibodies are related to the occurrence of disease relapses in patients with MS and that treatment with natalizumab drastically reduces both the relapse rate and IgG HHV-6 antibody titers. Based on these data, the authors highlight the potential role of these antibodies not only as predictive factors, but also as early biomarkers of drug response in patients with MS [ 70 ].…”