Interferon-beta in MS

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Quite contrary to the other therapy sections, this is no review. The reason for bringing this page is simply that I want to make the figure accessible; and the reason for not making a review is that this has been done already, that treatment with Interferon-beta [IFNB] does  not represent an alternative treatment but currently one of the few (probably the best) attempts to slower progression of the disease, and finally that the big labour associated with a literature survey is almost bound not to alter the before mentioned statement, although it might establish its background further

See addition below concerning neutralizing antibodies.

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It is my impression that

1. IFNB in the higher dosage (28-32 MIO units per week) produces the best results, as compared to the lower dosage of 6 MIO in a single weekly injection;

2. there is no therapeutic difference in activity between IFNB 1a and 1b;

3. cross-reaction makes a change of therapy under the impression of antibodies useless;

4. immunosuppressive therapy is inferior, but occasionally required in addition to IFNB; and

5. copolymer-A (glatimer racemate) and intravenous immunoglobulines, while not being well-defined drugs, exerts only an unspecified (irritative) immune response which makes them incomparable (possibly inferior) to IFNB.

6. IFN-Gamma has often been shown directly damaging in MS, IFN-alpha, while it has not been directly compared with IFNB, has some effect but is probably acting less convincing. Some hope is now carried on the newly synthetized IFN-tau - the future may show if it works.

It would certainly have looked more impressively if this was the conclusion of a large review: It is not, and you will only seldom find so sharply defined statements, for that reason we leave it as an impression.

With the injection of IFNB, the patient should try to find a new place each time, so that a new injection in the same area nay only take place after a certain span of time. Using the indication of the figure below, 1-2 months will pass before an area is approached again. Of course, other areas might be defined instead, it is only important that a schedule is made.
 

Figure: Daily injection sites for IFNB.
 

Addition:

A rare study form desires reference, partly for its conclusion, partly while it of the type I prefer (studying what happens to different patients) and not the unethical randomized placebo-controlled trials commented upon elsewhere (A Conflict to Come, Placebomania in MS-Studies, MS-Science 2004).

The Danish National IFN-beta Project [1] is the largest independent study that has examined the impact of neutralizing antibodies [NAbs] on the therapeutic effect of IFNB. The study comprised 541 patients, who all were treated with the same IFN[beta] preparation throughout the entire observation period, beginning during the years 1996 to 1999 in Denmark.

NAbs were found in 45,4% of 194 patients receiving IFNB-1B and 45,7%, the same incidence, in 162 patients receiving IFNB-1A three times weekly. In contrast, only 14.6 % of 185 patients, receiving IFNB-1A developed NAbs. This finding must, however, be balanced upon a lessened activity, assumed from the lower dosage (22 or 30 g weekly). The net effect upon the EDSS was not disclosed in this study.

The status at 12 months was somewhat predictive: if the 12-month status was negative, only 9%, 9%, 12%, and 15% became NAb positive after 2, 3, 4, and 5 years, respectively. Conversely, if the 12-month status was positive, the percentages of these patients who were still NAb positive after 2, 3, 4, and 5 years were 82%, 69%, 53%, and 46%, respectively

The name “neutralizing” is well selected, also what the effect concerns. The relapse-rate was 55% higher during NAb positive periods as compared with NAb negative ones. Again, this apparently clear statement is relativised through the chances for the NAb positive patient at 12 months to become NAb negative, which appear to be even after about 4.5 years.

I hope that other conclusions may be published from this exceptional investigation. Moreover, I hope that more will be published from such kind of studies, investigating various habits of thousands of patients over the years. But then, there are the double-blinded editors …

1. Sorensen PS, Ross C, Clemmesen KM, Bendtzen K, Frederiksen JL, Jensen K, Kristensen O, Petersen T, Rasmussen S, Ravnborg M, Stenager E, Koch-Henriksen N; Danish Multiple Sclerosis Study Group; Danish Interferon-beta Project. Antibodies to IFN-beta: the Danish National IFN-beta Project. Neurology 2003;61(Suppl 5):S27-8.

Written September 9, 2000, last revision Mar 31, 2004

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