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From Centro Riferimento Regionale Sclerosi Multipla (CReSM) & Neurobiologia Clinica, Ospedale Universitario San Luigi, Orbassano, Italy.
Address correspondence and reprint requests to Dr. Antonio Bertolotto, Centro Riferimento Regionale Sclerosi Multipla (CReSM) & Neurobiologia Clinica, Ospedale Universitario S. Luigi, Regione Gonzole 10, 10043, Orbassano, Italy; e-mail: sclerosi.multipla{at}sanluigi.piemonte.it
Objective: To analyze the impact of neutralizing antibodies (NAbs) on the clinical efficacy of IFNß.
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 IFNß 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 IFNß.
Received July 12, 2003. Accepted in final form January 29, 2004.
SM, AS, FG, RB, ADS, MC, and AB have been reimbursed by Shering, Serono, Biogen, Teva, Aventis, and Dompè Biotech for attending several conferences. AB received fees for speaking by Serono, Dompè Biotech, and Biogen. AB received funds for research and for members of the staff by Serono, Dompè Biotech, Aventis, and Biogen. Shering is the manufacturer of Betaferon. Serono is the manufacturer of Rebif. Biogen is the manufacturer of Avonex, and Dompè Biotech is the Italian distributor of Avonex.
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