Neutralizing 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.
In patients with relapsing-remitting MS who had been treated with interferon beta in the past, the relapse rate was higher and progression of disability faster in those who had neutralizing antibodies 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 associates.
They reviewed the medical records of 71 MS patients treated with interferon beta between 1994 and 2006. A median of 25 months after discontinuing therapy, 17 patients (24%) still had circulating neutralizing antibodies to interferon beta.
Patients with persistent antibodies were no different from those without them, even when considering potential predisposing factors such as age at MS onset, sex, MS subtype, disease duration, duration of interferon-beta therapy, and degree of disability at the start of treatment. The relapse rate was nearly 5 times higher in antibody-positive patients than in antibody-negative patients (Arch. Neurol. 2010; Feb. 8 [doi:10.1001/archneurol.2010.21
Patients with persistent neutralizing antibodies also showed faster progression of disability when evaluated using the Expanded Disability Status Scale.
“Most patients who discontinued interferon beta treatment because of perceived efficacy failure were not neutralizing-antibody positive,” the authors wrote. It is not yet clear why neutralizing antibodies to interferon beta can persist months or years after exposure to the antigen has ceased or how persisting antibodies exert their effect on MS activity.
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.”
The retrospective nature and the small sample of the study did not allow for definitive conclusions to be drawn, and causality could not 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, and working with some that have development programs for future drugs for the disease.