VANCOUVER, BC—No difference in serum vitamin D levels was found between patients with multiple sclerosis (MS) and positive anti-drug antibodies (ADA) vs. negative ADA in samples taken 1 year after interferon-β treatment was initiated, a study presented at the 68th AAN Annual Meeting has found.

A retrospective study of patients with MS tested for anti-interferon-β ADA in a central laboratory in Düsseldorf found a higher risk of ADA occurrence among those who initiated treatment in April, compared with other months of the year.

An estimated 10% to 30% of patients with MS treated with interferon-β develop ADAs, which can lead to treatment failure; therefore, it is important to limit their development.

To test the association of vitamin D levels with ADA, Signe Hässler, MD, of CESP, INSERM, Hôpital Paul Brousse, Villejuif, France, and colleagues conducted a case-control study nested on this cohort, measuring serum 25-OH-vitamin D.

“With a matched case-control study design we increased the chance to detect a real association between ADA and vitamin D levels,” noted Dr. Hässler, who is also with the ABIRISK Consortium in Brentford, Middlesex, UK.

The study included 126 pairs of patients matched for sex, age, type of interferon-β, and time of serum sample.

Conditional logistic regression of ADA occurrence by month of start of interferon-β therapy in the matched pairs showed an odds ratio of 2.43 (95% confidence interval [CI] 1.01–5.86; P=0.048), compared with a P-value of <0.0001 observed in the complete cohort.

When serum vitamin D level after more than 1 year of interferon-β therapy was examined by month of serum sampling using the complete cohort, ANOVA showed statistical significance for April–May (P=0.03); however, a Bonferroni-corrected t-test on all study patients found geometric mean vitamin D levels to be 13.80ng/mL for April–May and 21.88ng/mL  for October–November (P=0.015). “No other month comparisons were significant,” she noted.

Vitamin D serum levels were normalized by a logarithmic transformation. On univariate analysis, storage time, experimental batch, month of therapy start, sex, time since start of therapy, age, and latitude of sampling were not significant. Type of interferon-β was significant (P=0.05) and, on multivariate analysis, using intramuscular interferon-β-1a as the reference, subcutaneous interferon-β-1a, but not subcutaneous interferon-β-1b, remained significant (P=0.06).

“This difference may be best explained by a confounder effect, such as a more frequent prescription with interferon-β-1b to patients with a secondary progressive disease course,” Dr. Hassler noted. “This subgroup of patients may be more likely to suffer from vitamin D deficiency in consequence of a higher degree of motor disability, and the lack of sun exposure.”

Month of serum sample was significant on univariate analysis (P=0.03). On multivariate analysis, using April–May as the reference, October–November (P=0.003) and December–January (P=0.05) were significantly associated with the lowest vitamin D levels.

“We confirmed lowest seasonal serum vitamin D levels in April–May,” she noted. “However, our primary study outcome was negative: serum vitamin D levels at more than 1 year of interferon-β were not associated with ADA occurrence.

“Furthermore, month of therapy start was not associated with vitamin D level at more than 1 year of therapy, suggesting that vitamin D levels measured during this study cannot be inferred to be the levels that were present at baseline before start of therapy. We cannot exclude that a difference in serum vitamin D levels was present at baseline between patients who later became ADA-positive and ADA-negative, respectively: this difference might be masked by interferon-β effects and/or presence of ADA in the late serum samples that were available for this study.”

A prospective study is planned that will measure vitamin D at baseline and at 3 months, along with ADA status and titers at several time points between 0–18 months of therapy with interferon-β.