Neutralizing antibodies reduce the efficacy of βIFN during treatment of multiple sclerosis

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Abstract
Objective: To analyze the impact of neutralizing antibodies (NAbs) on the clinical efficacy of IFNβ. Methods: This was an open-label study involving 78 patients with multiple sclerosis treated with Betaferon 8 million IU (MIU) subcutaneously (SC) every other day (n = 20), Rebif 22 μg SC 3 times weekly (n = 25), or Avonex 30 μg IM once weekly (n = 33). Every 3 months, blood samples were collected and sera were analyzed for NAbs using an antiviral cytopathic effect assay. Patients were categorized according to their NAb status: NAb negative (NAb−); isolated NAb positive (NAb+), patients with ≥1 positive sample (titer ≥ 20); and persistent NAb+, patients with ≥2 consecutive positive samples (titer ≥ 20). Patients who were NAb− and persistent NAb+ were compared for relapse rate, time between first and second relapse, percentage of relapse-free patients, and percentage of patients who had a sustained progression of ≥1 point on the Expanded Disability Status Scale (EDSS). Results: The incidence of persistent NAb+ patients was 35% for Betaferon, 20% for Rebif, and 3% for Avonex. During IFNβ treatment, both NAb+ and NAb− patients showed a reduction in relapse rate; this reduction (25%) was not significant in NAb+ patients but was significant (67%; p < 0.0001) in NAb− patients. In addition, the mean relapse rate was higher (p = 0.039), mean time between first and second relapse was shorter (13 vs 21 months; p = 0.0064), and there was a trend suggesting that NAbs affected the probability of remaining relapse free (p = 0.08). A higher percentage of NAb+ patients versus NAb− patients had worsening of EDSS scores during follow-up (p = 0.013). Conclusion: Persistent NAbs significantly reduce the clinical efficacy of IFNβ.

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