Influence of interferon-beta therapy switching on neutralizing antibody titres: results from the Austrian Switch Study

Abstract

Neutralizing antibodies against interferon-beta are associated with a reduction of the efficacy of this drug. Continuing treatment leads to a decline or even loss of neutralizing antibodies over years. No strategies are currently available to shorten the period of neutralizing antibody positivity. The objective of this study was to investigate the effect of switching between high and low immunogenic interferon-beta products on neutralising antibody titres. Twenty-four patients treated with the subcutaneously administered interferon-beta 1b or 1a and high titres of neutralizing antibodies were included. At baseline interferon-beta therapy was interrupted for 3 months and two pulses of high dose methylprednisolone were applied. Patients were then randomized to receive either the previous interferon-beta preparation or the low immunogenic intramuscular interferon-beta 1a. The primary end-point was the change of neutralizing antibody titres 12 months after randomization. Twelve patients were switched to interferon-beta 1a intramuscularly and 12 patients remained on previous treatment. Median neutralizing antibody titres were 846 NU at baseline and 196 NU at the end of the study. The median change of neutralizing antibody titres did not differ significantly between therapy switchers and non-switchers. Baseline and final neutralizing antibody titres correlated significantly. In conclusion, neither switching nor continuous therapy with any subcutaneous interferon-beta preparation significantly changed neutralizing antibody titres.

A 2-year observational study of patients with relapsing-remitting multiple sclerosis converting to glatiramer acetate from other disease-modifying therapies: the COPTIMIZE trial

“…Converting therapy within the IFN-β class may not always benefit the patient [15]. Patients who present with neutralizing antibodies during IFN treatment do not benefit from converting from one IFN to another or from continuous therapy with any subcutaneous IFN-β preparation [15].…”

“…Patients who present with neutralizing antibodies during IFN treatment do not benefit from converting from one IFN to another or from continuous therapy with any subcutaneous IFN-β preparation [15]. Conversely, studies have demonstrated that there is a clinical benefit in changing either from one class of first-line DMT to another or to second-line treatments [13, 16–18].…”

Prevalence of anti-drug antibodies against interferon beta has decreased since routine analysis of neutralizing antibodies became clinical practice

“…Multiple Sclerosis Journal 18 (12) the patients who develop NAbs remain positive for years, although around one-third of the NAb positive patients, in particular Betaferon-treated patients, may revert to negativity during continued treatment. 8 NAbs can also persist for up to five years, but probably longer, even if the IFNβ treatment is discontinued.…”

The Impact of Methylprednisolone Pulses during Relapses of Multiple Sclerosis on the Kinetics of Anti-Interferon-Beta Antibodies

“…First, given the knowledge of steroid effects on any antibody titers, a 3-month follow up would be optimal. A previous study in a smaller number of relapse-free patients who had developed Nabs and received 2 short MP pulses 6 weeks apart, observed an initial titer decrease followed by an increase at 3 months [25] . In our study, the medium-and long-term kinetics of anti-IFNβ antibodies and in particular, the persistence of the high rate of seronegativity conversion beyond D30 remains unknown.…”