Neurologist in training

Interferon-beta (b-IFN) represents the first-line immunomodulatory treatment for patients with relapsing-remitting multiple sclerosis (MS). However, over the last decade increased awareness of autoantibodies against b-IFN has emerged. These may develop in a variable percentage of treated subjects (2–45%), dependingon theb-IFNcompound and the assay method, and impair the therapeutic efficacy of interferons [1]. Recent European guidelines recommend measurement of neutralizing antibodies to be performed in all patients at 12 and 24 months of therapy, in specialized laboratories with validated methods. Follow-up of titers is not judgednecessary in subjectswho remain negative during this period, but therapy with b-IFN should be discontinued in those with high titers [2]; however, controversies with North American experts exist [3]. In this context, two recent studies carried out in Scandinavia attempted to investigate the natural course and the impact of steroids on these autoantibodies. In order to determine spontaneous titers’ fluctuation over time, a Swedish group investigated, retrospectively, a cohort of 822 MS patients treated with the three commercially available b-IFN compounds, who benefited from at least two autoantibodies testing at one year interval or more. They chose a cutoff of 150 TRU/ml for biological relevancy [4]. Overall, 72% of patients did not show any titer variation between the assays. This percentage was even higher in subjects at the two extremes (i.e., 97% with no antibodies, 91%with very high titers), while those with moderate titers tended to fluctuate more often. This trend was not influenced by treatment duration, b-IFN type, or the length of sampling interval. Interestingly, a decrease over time in antibodies titers appeared more often than an increase. The studywas somewhat limited by its selection bias, and the use of laboratory assays prevents direct comparisons with other studies [5]. Nevertheless, these results may further support the practice of discontinuing b-IFN administration in subjects with high titers, and suggest some usefulness of repeated measurements in patients in the “grey zone”. A Danish team designed a non-randomized interventional trial to assess the usefulness of the co-administration of 500mgofmethylprednisolone orally (three daysmonthly, for 6 months) in subjects with positive autoantibodies (cutoff not clear) combined with an absent in vivo response to b-IFN (tested using a cytopathic effect assay) [6]. There were 35 patients in the treatment sample, and 38 controls (subjects that chose not to undergo steroid administration and Neurologist in training