By Mary Ann Moon  |  Mon, 08 Feb 2010 21:00 GMT
Elsevier Global Medical NewsBreaking NewsNeutralizing antibodies to interferon-beta not only persist in some multiple sclerosis patients who discontinue the recombinant-DNA treatment, they also appear to worsen the disease course, according to a report published online Feb. 8 in the Archives of Neurology. In a retrospective study of 71 patients with relapsing-remitting MS who had been treated with interferon-beta in the past, the relapse rate was higher and progression of disability was faster in those who had neutralizing antibodies to the drug in their circulation than in those who did not have the antibodies, said Dr. Laura F. van der Voort of Vrije University Medical Center, Amsterdam, and her associates. “The clinical significance of anti–interferon-beta neutralizing antibodies continues to be a controversial issue in the MS community,” and the clinical effects of antibodies that persist after treatment cessation “are largely unknown,” the researchers noted. They studied the issue by reviewing the medical records of 71 MS patients treated with interferon-beta at a single center between 1994 and 2006. A median of 25 months after discontinuing the therapy, 17 (24%) of these patients were found to still have circulating neutralizing antibodies to interferon-beta. Patients who had persistent antibodies were no different from those who did not in any of the potential predisposing factors that were assessed in this study. This included patient age at onset of MS, patient sex, subtype of MS, disease duration, duration of interferon-beta therapy, and degree of disability at the beginning of treatment. The relapse rate was nearly five times higher among antibody-positive patients than among antibody-negative patients, Dr. van der Voort and her colleagues said (Arch. Neurol. 2010;67 [doi10.1001/archneurol.2010.21]). In addition, patients with persistent neutralizing antibodies showed faster progression of disability when evaluated using the Expanded Disability Status Scale. “However, it must be noted that most patients who discontinued interferon-beta treatment because of perceived efficacy failure were not neutralizing-antibody positive,” the investigators said. It is not yet clear why neutralizing antibodies to interferon-beta are able to persist months or years after exposure to the antigen has ceased. It also is not known how persisting antibodies exert their effect on MS activity, they noted. It is possible that the antibodies affect endogenous interferon pathways, causing “a more proinflammatory modification of the immune system. Alternatively, the tendency to develop and sustain anti–interferon-beta antibodies might be a reflection of a more active immune system,” Dr. van der Voort and her associates said. “Obviously, the retrospective nature and the small sample of our study do not allow for definitive conclusions to be drawn, and causality cannot be proven,” they added. This study was supported in part by a targeted research project on neutralizing antibodies funded by the European Commission. Dr. van der Voort reported being involved in clinical trials of companies that market drugs for MS, including Schering AG, Biogen Idec, Serono, and Teva, and working with companies that have development programs for future drugs for the disease.Subject Codes: top_stories; neurology; http://www.imng.com February 08, 2010   04:00 PM EST