All About Multiple Sclerosis

More MS news articles for June 2004

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

Neurology. 2004 Jun 8;62(11):2031-7
Malucchi S, Sala A, Gilli F, Bottero R, Di Sapio A, Capobianco M, Bertolotto A.
Centro Riferimento Regionale Sclerosi Multipla (CReSM) & Neurobiologia Clinica, Ospedale Universitario San Luigi, Orbassano, Italy.


To analyze the impact of neutralizing antibodies (NAbs) on the clinical efficacy of IFNbeta.


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 micro g SC 3 times weekly (n = 25), or Avonex 30 micro g 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 > or =1 positive sample (titer > or = 20); and persistent NAb+, patients with > or =2 consecutive positive samples (titer > or = 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 > or =1 point on the Expanded Disability Status Scale (EDSS).


The incidence of persistent NAb+ patients was 35% for Betaferon, 20% for Rebif, and 3% for Avonex.

During IFNbeta 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).


Persistent NAbs significantly reduce the clinical efficacy of IFNbeta.