Neutralizing Antibodies in MS Treatments

What are Neutralizing Antibodies and is this a Bad Sign?

MRI scans of a brain showing multiple sclerosis.
MRI scans of a brain showing multiple sclerosis.. maciu17/Getty Images

Many people with relapsing-remitting MS take an interferon beta disease-modifying therapy, like Avonex, Rebif, or Betaseron. When taking these medications, a person can develop neutralizing antibodies, which essentially inhibits or neutralizes the effects of the interferon therapy -- sounds bad, right?

Well, there is some debate as to the true clinical impact of neutralizing antibodies, meaning how it really affects a patient and their MS disease progression.

What if I Have Neutralizing Antibodies?

According to the American Academy of Neurology, it's likely that high-titers of neutralizing antibodies in a person's bloodstream (meaning high levels of the neutralizing antibodies) are associated with a reduced effectiveness of interferon beta therapy -- as evidenced by a person's symptoms and their MRI findings. This means that with high levels of neutralizing antibodies, a person will likely not respond to the medication. What constitutes "high-titers" is not quite defined yet, but is believed to be greater than 200NU/mL with interferon beta-1b (e.g. Betaseron) and greater than 500NU/mL with interferon beta-1a (e.g. Avonex, Rebif).

Am I at Risk for Developing Neutralizing Antibodies?

It's really unknown. About a third or more of patients with MS treated with interferon-beta medications develop neutralizing antibodies, and this usually occurs between 6 to 18 months on therapy.

Whether or not you develop neutralizing antibodies likely depends on a number of factors including:

  • dose of the interferon-beta therapy
  • route of administration, like intramuscular (into the muscle) versus subcutaneous (into the fat)
  • frequency of administration
  • formulation

For instance, it seems that there is less of a chance of developing neutralizing antibodies with Avonex, an intramuscular injection once a week, as compared to Betaseron or Rebif, which are given subcutaneously multiple times a week.

Although researchers note this is all really hard to determine because neutralizing antibodies can disappear and often do in most patients. This is true even when they continue interferon-beta treatment, especially if they had low-titers of neutralizing antibodies to begin with.

Testing for Neutralizing Antibodies

There is no hard and fast guideline about if and when to check for neutralizing antibodies, and how to precisely interpret the results.

That being said, one strategy is to check an antibody level at 12 months and then again at 24 months. This is because most people develop neutralizing antibodies within 24 months of starting interferon beta therapy. If negative at both these intervals, a neurologist will likely discontinue checking antibodies and then recheck only in the event of a relapse.

If a person develops high titers persistently (on multiple checks), the medication will likely be discontinued.

That being said, a neurologist will most likely discontinue interferon beta therapy and switch a person to another disease-modifying therapy if their MS worsens, regardless of the presence (or absence) of neutralizing antibodies.

Bottom Line

We know that neutralizing antibodies develop in some people on interferon beta therapies, and that high levels of these antibodies are linked to diminished effectiveness of the medication. Whether or not you get tested for the antibodies and how you get tested is a personal decision between you and your doctor.

Sources:

AAN Evidence Report Summary for Clinicians (2007): Neutralizing Antibodies to Interferon Beta: Assessment of their Clinical and Radiographic Impact. Retrieved January 18th 2016.

Creeke PI & Farrell RA. Clinical testing for neutralizing antibodies to interferon-β in multiple sclerosis. Ther Adv Neurol Disord. 2013 Jan;6(1):3-17.

Hegen H et al. Early detection of neutralizing antibodies to interferon-beta in mutliple sclerosis patients: binding antibodies predict neutralizing antibody development. Mult Scler. 2014 Apr;20(5):577-87.

Sorensen PS. Neutralizing Antibodies Against Interferon-Beta. Ther Adv Neurol Disord. 2008 Sep;1(2):62-78.

DISCLAIMER: The information in this site is for educational purposes only. It should not be used as a substitute for personal care by a licensed physician. Please see your doctor for diagnosis and treatment of any concerning symptoms or medical condition.

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