Neutralizing anti-IFN-β antibodies
How much more evidence do we need to use them in practice?
Citation Manager Formats
Make Comment
See Comments
![Loading Loading](https://n.neurology.org/sites/all/modules/contrib/panels_ajax_tab/images/loading.gif)
This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased.
Neutralizing antibodies (NAbs) are a major hurdle to the successful use of biologics in clinical practice. The impact of NAbs is obvious in biologic systems with no redundancy. NAbs induced in response to treatment with recombinant erythropoietin or thrombopoietin cause life-threatening complications of pure red cell aplasia and thrombocytopenia as a direct result of inhibiting the activity of the endogenous hormones. For the type 1 interferons (α and β), NAbs have not yet been shown to have untoward biologic effects. This may relate to the fact that IFNα and IFNβ have overlapping biologic activities or that they are produced locally as autocrine or paracrine mediators and are therefore less likely to be exposed to NAbs. In comparison, the evidence that NAbs interfere with the therapeutic effect of type 1 interferons is much clearer. In subjects with multiple sclerosis (MS), NAbs inhibit the induction of IFNβ-specific gene products and lessen the benefit of IFNβ on both MRI activity and relapse rate. Furthermore, three articles in this issue of Neurology show that NAbs1,2 impact negatively on disease progression and are likely to persist.3
NAbs do not appear until 6 to 24 months after IFNβ is initiated and do not have consistently measurable effects in trials of less than 2 years' duration. In the pivotal IFNβ-1b study (Betaseron/Betaferon), the clinical impact of NAbs on MS relapse rate only became apparent after 18 months of therapy.4 In the subcutaneous IFNβ-1a PRISMS study (Rebif) there were no reported differences in the clinical and MRI endpoints between NAb+ and NAb− patients at 2 years.5 However, in the 4-year extension phase of PRISMS, the relapse rate was 60% greater (0.81 vs 0.50, p = 0.002), the median number of T2 active lesions was five times greater (1.4 vs 0.3, p < 0.01), and …
AAN Members
We have changed the login procedure to improve access between AAN.com and the Neurology journals. If you are experiencing issues, please log out of AAN.com and clear history and cookies. (For instructions by browser, please click the instruction pages below). After clearing, choose preferred Journal and select login for AAN Members. You will be redirected to a login page where you can log in with your AAN ID number and password. When you are returned to the Journal, your name should appear at the top right of the page.
AAN Non-Member Subscribers
Purchase access
For assistance, please contact:
AAN Members (800) 879-1960 or (612) 928-6000 (International)
Non-AAN Member subscribers (800) 638-3030 or (301) 223-2300 option 3, select 1 (international)
Sign Up
Information on how to subscribe to Neurology and Neurology: Clinical Practice can be found here
Purchase
Individual access to articles is available through the Add to Cart option on the article page. Access for 1 day (from the computer you are currently using) is US$ 39.00. Pay-per-view content is for the use of the payee only, and content may not be further distributed by print or electronic means. The payee may view, download, and/or print the article for his/her personal, scholarly, research, and educational use. Distributing copies (electronic or otherwise) of the article is not allowed.
Letters: Rapid online correspondence
REQUIREMENTS
You must ensure that your Disclosures have been updated within the previous six months. Please go to our Submission Site to add or update your Disclosure information.
Your co-authors must send a completed Publishing Agreement Form to Neurology Staff (not necessary for the lead/corresponding author as the form below will suffice) before you upload your comment.
If you are responding to a comment that was written about an article you originally authored:
You (and co-authors) do not need to fill out forms or check disclosures as author forms are still valid
and apply to letter.
Submission specifications:
- Submissions must be < 200 words with < 5 references. Reference 1 must be the article on which you are commenting.
- Submissions should not have more than 5 authors. (Exception: original author replies can include all original authors of the article)
- Submit only on articles published within 6 months of issue date.
- Do not be redundant. Read any comments already posted on the article prior to submission.
- Submitted comments are subject to editing and editor review prior to posting.
You May Also be Interested in
Dr. David Beversdorf and Dr. Ryan Townley
► Watch
Related Articles
Topics Discussed
Alert Me
Recommended articles
-
Articles
Neutralizing antibodies and efficacy of interferon β-1aA 4-year controlled studyL. Kappos, M. Clanet, M. Sandberg-Wollheim et al.Neurology, July 11, 2005 -
Articles
Interferon β-1a in MSResults following development of neutralizing antibodies in PRISMSGordon S. Francis, George P.A. Rice, Jonathan C. Alsop et al.Neurology, July 11, 2005 -
Articles
MRI metrics as surrogate endpoints for EDSS progression in SPMS patients treated with IFN β-1bM. P. Sormani, P. Bruzzi, K. Beckmann et al.Neurology, May 13, 2003 -
Articles
A Phase II study of the safety and efficacy of teriflunomide in multiple sclerosis with relapsesP. W. O’Connor, D. Li, M. S. Freedman et al.Neurology, March 27, 2006