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LETTERS TO THE EDITOR

REVISITING INTERFERON TREATMENT FOR MULTIPLE SCLEROSIS

I am writing to register my displeasure with the article entitled “Higher Dose, Higher Frequency Improves Interferon Treatment for MS” in Neurology Today (August 2000, pages 40–41). By using fragments of my responses during the interview out of the context of the full answer, virtually every comment attributed to me distorts my true view and the intent of my answers.

To clarify, these are my positions on the issues raised in the article:

  • The trend in the MS field of studies taking short-cuts in some important aspects of trial design (as illustrated by the study of Luca Durelli, MD, and others) is a problem.
  • The lack of blinding of subjects and investigators coupled with the use of a highly subjective primary outcome measure, relapses, is a major flaw in the study of Dr. Durelli and others. Corroboration of the treatment effect on relapses by benefit on MRI is reassuring but does not obviate this shortcoming of the study. While superficially “the results of the study are pretty convincing,” lack of blinding raises a prominent red flag.
  • All of the interferon beta drugs are immunogenic to varying degrees and elicit a humoral immune response that includes antibodies that block interaction of the interferon beta ligand with its receptor, so-called neutralizing antibodies (NAbs). The only known mechanism of action of the interferon beta involves binding to a single receptor. NAbs clearly block the in vitro and in vivo biologic response to interferon beta, and, thus, would be expected also to block the clinical benefit of interferon beta in MS. However, the data concerning the clinical significance on NAbs in MS are suggestive, but they are not conclusive. In my opinion, the reason that this last point remains unproven is that none of the studies performed to date has been adequately designed to address the issue.
  • The available therapies for MS are only partly effective for patients as a group. There are patients with breakthrough disease on standard therapy and patients with worrisome prognostic features that are unlikely to respond to standard therapy. Yes, we consider higher doses of interferon in such patients. We also consider other approaches such as combination therapy.

I am not objecting to the content of the article per se, only to the inaccurate reporting of my views. I may have been partly to blame for the confusion by trying to provide balanced responses to the questions posed to me and attempting not to be too harshly critical of a colleague. However, I do not think that I was entirely to blame. I certainly will be much more careful in choosing my words when dealing with your publication in the future.