Neutralising antibodies to interferon beta during the treatment of multiple sclerosis
- 1Department of Neuroinflammation, Institute of Neurology, London, UK
- 2William C Baird Multiple Sclerosis Research Center, State University of New York at Buffalo, USA
- 3Department of Neurology, University of Innsbruck, Innsbruck, Austria
- Correspondence to: Dr G Giovannoni, Department of Neuroinflammation, Institute of Neurology, Queen Square, London WC1 3BG, UK; G.Giovannoni{at}ion.ucl.ac.uk
The significance of the generation of antibodies in response to interferon beta administration is discussed
Patients with multiple sclerosis (MS) receiving interferon beta may develop neutralising anti-interferon beta antibodies (NABs) during treatment. These NABs are clinically relevant and reduce the clinical efficacy of interferon beta. Although there is lack of consensus on how these antibodies should be measured, the relative prevalence of NABs induced by different interferon beta products seems to be consistent between studies. Subcutaneous interferon beta-1b (Betaferon) is the most immunogenic, followed by subcutaneous interferon beta-1a (Rebif), with intramuscular interferon beta-1a (Avonex) being the least immunogenic. Differences between the interferon beta products with regard to their structure/biochemistry, formulation, dose, route of administration, and dose frequency are likely to contribute to these observed differences in immunogenicity. This editorial highlights the consequences of NABs formation on the biological and clinical activity of interferon beta and the implications NABs have for the practicing neurologist and patient with MS.
BACKGROUND
Interferon beta is an established first line treatment in relapsing remitting MS.1–5 As has been observed with other biological agents,6 antibodies are sometimes generated in response to interferon beta administration.7–10 A subset of these antibodies inhibit or neutralise (NABs) the biological activity of interferon beta. This editorial will attempt to clarify technical issues of NABs measurement, the clinical significance of NABs, differences between the currently available interferon beta products, and the clinical implications of NAB development.
ANTIBODIES ELICITED BY INTERFERON BETA
An immune response against protein based drugs is not unusual.6 For example, neutralising antibodies have been reported during treatment with interferon alfa for viral hepatitis B and C, hairy cell leukaemia, and other types of cancer,9,10 during treatment with bovine or porcine insulin for diabetes mellitus,11 with human growth hormone 12 and factor VIII and IX therapy in …
