Neutralizing antibodies against interferon β: fluctuation is modest and titre dependent

Neutralizing antibody (NAb) titres may vary over time and thereby some patients can either lose or regain therapeutic effect of interferon beta (IFNbeta). We assessed NAb titres in a large sample of multiple sclerosis (MS) patients to identify the pattern of fluctuation during 1-3 years.

Data from IFNbeta-treated MS patients who had been tested for NAbs twice (n = 822) were analysed. NAb titres were compared between the first and the second samples across the critical NAb level of 150 TRU/ml, which we have previously reported to correlate with loss of bioactivity.

Of patients with NAb titres high enough to indicate loss of bioactivity (>150 TRU/ml) in the first analysis 15% showed titres low enough to indicate a regained bioactivity. Conversely, 6% of those without detectable NAbs or NAb titres below the critical level of 150 TRU/ml had shifted to titres above this limit, indicating potential loss of bioactivity. Fluctuation did not differ between IFNbeta preparation used, treatment duration or sampling interval.

A first NAb test is prognostic for the NAb status during the coming 1-3 years. Choice of IFNbeta preparation had no influence on the chance of reverting to lower levels once NAb titres are high.