Aug 01, 2005
Over the past decade, there has been debate among MS specialist physicians about the role of neutralizing antibodies (NAbs) in treatment decisions and treatment outcomes. This document summarizes the basic issues in the scientific literature.
Antibodies are proteins of the immune system that arise in response to foreign substances, including viruses and bacteria. Some people who receive an interferon beta medication (Avonex®, Betaseron®, Rebif®) develop a form of antibody to the injected protein. This is called a "neutralizing antibody" (NAb) because it interferes with-or neutralizes-biological properties of the interferon. There is no convincing evidence at this time that antibodies that develop in people taking glatiramer acetate have any clinical significance.
Not all people taking an interferon medication develop NAbs. When they occur, NAbs typically develop 12-18 months after the start of treatment.
Studies indicate that the frequency of development of NAbs differs among the interferon products, with Avonex® (interferon beta 1a —intramuscular injection once per week) producing NAbs less often than either Rebif® (interferon beta-1a —subcutaneous injection three times weekly) or Betaseron® (interferon beta-1b —subcutaneous injection every other day). It is unclear whether these differences are related to different manufacturing procedures, dosage levels, frequencies of doses, and/or routes of delivery.
Studies indicate that NAbs may have an impact on clinical effectiveness of a medication: In individuals who maintain a high NAb level over time, the clinical efficacy of the medication seems to be reduced; relapse rates and MRI activity are higher than in those individuals who remain NAb negative. Some recent studies suggest that the disease progresses faster in those who develop NAbs.
NAbs seem to disappear naturally after a certain period of time in some patients. Therefore, it is difficult to make treatment decisions based on the results of a single assay, particularly if the person is continuing to do well clinically (i.e., relapse rate, symptoms, MRI activity). Repeat NAb-positive assays over time in a person who is doing less well clinically, however, might suggest that a change to a non-interferon medication would be helpful. Since a person who makes NAbs to one of the interferon preparations will also have them to others, switching to another interferon preparation would not be beneficial.
Some data concerning NAbs remain difficult to interpret-and therefore controversial-for several reasons: Studies of NAbs have used different measurement tools (assays), different criteria for interpreting the results of the assays, different statistical strategies for evaluating the data, and different populations of people.
Although a variety of assays have been used in clinical studies the NAbFeron™ Antibody Test, (Athena Diagnostics) is the only commercially-available NAb assay. The Athena Diagnostic Web site offers:
NAbs seem to have an important impact on relapse rates and lesion development on MRI, and probably on disease progression as well. However, we are still learning how best to use this information in clinical practice.
Because, some people appear to do quite well on an interferon medication in spite of testing positive for NAbs, while others appear to do poorly on an interferon medication even in the absence of NAbs, many MS specialists believe that treatment decisions are best made by evaluating how a person is doing clinically rather than by the results of a NAb assay alone. A change to a non-interferon medication might be considered in a person whose disease remains active and who tests positive for NAbs on more than one occasion.
The data demonstrating differential frequency of NAb development among the interferon products must be weighed against the data indicating that higher-dosed, more frequently administered formulations of interferon beta may provide better short-term clinical efficacy than lower, less frequently dosed formulations of interferon beta in relapsing MS.