Impact of binding and neutralizing antibodies on the clinical and radiologic efficacy of Interferon Beta treatment in patients with multiple sclerosis

PurposeInterferon beta (IFNß) is one of the first line of immune treatment options for multiple sclerosis (MS). Repeated IFNß injections may induce IFNß antibody production in some patients. Such antibodies are called binding antibodies (BAbs), which do not affect the biological activity of the molecule, and neutralizing antibodies (NAbs), which are associated with a decrease in the efficacy of the treatment. However, the influence of these antibodies are subject of an ongoing debate. The objective of this study is to assess the frequency of BAbs and NAbs, and to evaluate the impact of these antibodies, from the clinical and radiologic aspects in patients with MS.MethodsOne hundred and two MS patients, treated only with IFNß for at least 18 months, were included into the study. Samples were screened for BAb, using capture enzyme-linked immunosorbent assay (cELISA), and NAbs were detected via Myxovirus protein A (MxA) messenger RNA (mRNA) induction assay (real-time polymerase chain reaction-PCR), first at the time of study and later, the following year. Relapse rate and Expanded Disability Status Scale (EDSS) were used to assess the clinical impact. Hyperintense lesions on T1-weighted post-gadolinium sequences and T2 lesion volume were used as magnetic resonance imaging (MRI) parameters.ResultsOf 49 patients treated with IFNß-1b, 40.8 % were BAb positive at the beginning of our study, whereas of 40 patients treated with IFNß-1a SC, 15 % were BAb positive; and of 13 patients treated with IFNß-1a IM, 7.7 % were BAb positive. NAbs were detected in 12.2 % of IFNß-1b treated patients, and in 7.5 % of IFNß-1a SC treated patients, but none of the IFNß-1a IM treated patients had detectable NAbs. Persistent NAb positivity was found 5.2%. At least half of the persistent NAb positive patients were observed to have relapses during follow-up (p=0.330). The mean relapse rate difference was significantly higher in persistent NAb negative patients than in persistent NAb positive patients (p=0.024). There was no convincing effect on progression of disability. It was shown that persistent NAb positivity had no effect on T2 lesion volume and contrast enhancing lesions in MRI.ConclusionIn this study, the frequency of NAb positive patients were lower when compared to other similar studies. This might be due to genetic features of Turkish MS patients or long-term efficacy of the drug. Consistent with the results to other studies, IFNß-1b was found more immunogenic than IFNß-1a SC, and IFNß-1a SC was more immunogenic than IFNß-1a IM. NAbs produced against IFNß reduce the therapeutic benefits measured by relapses and MRI activity. Data from this study suggest that patients may become unresponsive to IFNß therapy even when the frequency of BAbs and NAbs does not prove to be as high as those in the literature.