Dataset Information

Effect of vitamin D on MS activity by disease-modifying therapy class.

ABSTRACT:

Objective

To determine whether vitamin D status predicts disease activity in patients with multiple sclerosis (MS) taking interferon-? (IFN), glatiramer acetate (GA), and fingolimod (FTY).

Methods

Participants (n = 324) with relapsing-remitting MS on IFN (96), GA (151), or FTY (77) were identified from the Comprehensive Longitudinal Investigation of MS at Brigham and Women's Hospital (CLIMB) Study at the Partners MS Center. FTY-treated participants were analyzed separately because of differences in selection. Serum vitamin 25(OH)D concentration was adjusted for season. We evaluated the relationship between 25(OH)D tertile and time to relapse or gadolinium-enhancing lesion using a Cox model adjusted for age, sex, and disease duration.

Results

Higher 25(OH)D was associated with longer time to the combined endpoint in the overall IFN/GA cohort (p for trend = 0.042; hazard ratio [HR] = 0.77) and in the IFN subgroup (HRIFN = 0.58; p IFN = 0.012), but not in GA-treated participants (p = 0.50; HR = 0.89). For gadolinium-enhancing lesions alone, there was a significant association observed in GA and IFN subgroups, although the effect was more pronounced on IFN (HRGA = 0.57; p GA = 0.039 vs HRIFN = 0.41; p IFN = 0.022). No significant associations were found for relapses. For FTY, higher 25(OH)D was associated with longer survival for the combined endpoint (HRFTY = 0.48; p FTY = 0.016) and for relapses (HRFTY = 0.50; p FTY = 0.046), but not for gadolinium-enhancing lesions.

Conclusions

Disease activity generally improved with higher 25(OH)D, but this study raises the question of effect modification by treatment class.

SUBMITTER: Rotstein DL

PROVIDER: S-EPMC4630683 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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Publications

Effect of vitamin D on MS activity by disease-modifying therapy class.

Rotstein Dalia L DL Healy Brian C BC Malik Muhammad T MT Carruthers Robert L RL Musallam Alexander J AJ Kivisakk Pia P Weiner Howard L HL Glanz Bonnie B Chitnis Tanuja T

Neurology(R) neuroimmunology & neuroinflammation 20151029 6

<h4>Objective</h4>To determine whether vitamin D status predicts disease activity in patients with multiple sclerosis (MS) taking interferon-β (IFN), glatiramer acetate (GA), and fingolimod (FTY).<h4>Methods</h4>Participants (n = 324) with relapsing-remitting MS on IFN (96), GA (151), or FTY (77) were identified from the Comprehensive Longitudinal Investigation of MS at Brigham and Women's Hospital (CLIMB) Study at the Partners MS Center. FTY-treated participants were analyzed separately because ...[more]

PMID: 26568968

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Project description:BackgroundIn patients with Multiple Sclerosis (pwMS) disease-modifying therapies (DMTs) affects immune response to antigens. Therefore, post-vaccination serological assessments are needed to evaluate the effect of the vaccine on SARS-CoV-2 antibody response.MethodsWe designed a prospective multicenter cohort study enrolling pwMS who were scheduled for SARS-Cov-2 vaccination with mRNA vaccines (BNT162b2, Pfizer/BioNTech,Inc or mRNA-1273, Moderna Tx,Inc). A blood collection before the first vaccine dose and 4 weeks after the second dose was planned, with a centralized serological assessment (electrochemiluminescence immunoassay, ECLIA, Roche-Diagnostics). The log-transform of the antibody levels was analyzed by multivariable linear regression.Findings780 pwMS (76% BNT162b2 and 24% mRNA-1273) had pre- and 4-week post-vaccination blood assessments. 87 (11·2%) were untreated, 154 (19·7%) on ocrelizumab, 25 (3·2%) on rituximab, 85 (10·9%) on fingolimod, 25 (3·2%) on cladribine and 404 (51·7%) on other DMTs. 677 patients (86·8%) had detectable post-vaccination SARS-CoV-2 antibodies. At multivariable analysis, the antibody levels of patients on ocrelizumab (201-fold decrease (95%CI=128-317), p < 0·001), fingolimod (26-fold decrease (95%CI=16-42), p < 0·001) and rituximab (20-fold decrease (95%CI=10-43), p < 0·001) were significantly reduced as compared to untreated patients. Vaccination with mRNA-1273 resulted in a systematically 3·25-fold higher antibody level (95%CI=2·46-4·27) than with the BNT162b2 vaccine (p < 0·001). The antibody levels on anti-CD20 therapies correlated to the time since last infusion, and rituximab had longer intervals (mean=386 days) than ocrelizumab patients (mean=129 days).InterpretationIn pwMS, anti-CD20 treatment and fingolimod led to a reduced humoral response to mRNA-based SARS-CoV-2 vaccines. As mRNA-1273 elicits 3·25-higher antibody levels than BNT162b2, this vaccine may be preferentially considered for patients under anti-CD20 treatment or fingolimod. Combining our data with those on the cellular immune response to vaccines, and including clinical follow-up, will contribute to better define the most appropriate SARS-CoV-2 vaccine strategies in the context of DMTs and MS.FundingFISM[2021/Special-Multi/001]; Italian Ministry of Health'Progetto Z844A 5 × 1000'.

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Dataset Information

Effect of vitamin D on MS activity by disease-modifying therapy class.

Objective

Methods

Results

Conclusions

Publications

Effect of vitamin D on MS activity by disease-modifying therapy class.

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