More MS news articles for Nov 2001

Should I Double the IM Dose of Interferon beta-1a for My Patients With Multiple Sclerosis?

http://neurology.medscape.com/Medscape/Neurology/AskExperts/MS/2001/11/NEUR-ae102.html

Question

With preliminary evidence showing that high-dose/frequent-dose subcutaneous interferon beta-1a may be more effective than the lower-dose/once-weekly IM formulation, would it make sense to double the dose of the IM formulation, pending the availability of the subcutaneous preparation?

Response

from Mark S. Freedman, MD, 11/15/01

Three interferon formulations have been studied extensively for treating patients with multiple sclerosis. They are intramuscular interferon beta-1a (IM IFNbeta-1a), subcutaneous interferon beta-1a (SC IFNbeta-1a), and interferon beta-1b (IFNbeta-1b). IM IFNbeta-1a and IFNbeta-1b are already FDA-approved, whereas SC IFNbeta-1a is awaiting FDA approval.

At least 2 trials have demonstrated that not only higher but also more frequent doses of interferons are superior to the standard once-weekly regimen of IM IFNbeta-1a. In the EVIDENCE trial, SC IFNbeta-1a was given 3 times weekly at a dose of 44 mcg (ie, total weekly dosage of 132 mcg), and this regimen demonstrated a significantly greater effect at reducing relapse rates and on MRI activity than did IM IFNbeta-1a given at the recommended, once-weekly dose of 30 mcg. The INCOMIN study in Italy pitted the same once-weekly dosage of IM IFNbeta-1a against the recommended dosage of IFNbeta-1b, 250 mcg, given every other day (ie, total weekly dosage of 875 mcg), and found after 1 year that patients receiving IFNbeta-1b experienced fewer relapses and less MRI activity compared with those receiving IM IFNbeta-1a. This finding persisted into the second year of the study (results presented at the 17th Congress of the European Committee for Treatment & Research in Multiple Sclerosis [ECTRIMS], Dublin, Ireland, September 12-15, 2001).

IM IFNbeta-1a and SC IFNbeta-1a are both forms of the same molecule; IFNbeta-1b is a different interferon molecule and hence is not comparable on a mass basis. Nevertheless, the pharmacologic activity of the weekly IFNbeta-1b dosage is much closer to that resulting from the weekly dosage of SC IFNbeta-1a than to that produced by the IM IFNbeta-1a dosage.

A study comparing double-dose IM IFNbeta-1a (60 mcg/week) to the standard dose of 30 mcg/week found no substantial superiority in the higher dose. The reason for this is probably not only the dosing issue, but the frequency as well. Both SC IFNbeta-1a and IFNbeta-1b are given more frequently and this may account for their clinical superiority in these comparative trials. Thus, it would make no sense to simply double the IM IFNbeta-1a dose on a given day, but rather to give it 2 or even 3 times weekly. The fact that it is given by intramuscular injection makes a more frequent regimen less attractive, however. Twice-weekly administration of IM IFNbeta-1a would increase the dosage to 60 mcg (2 x 30 mcg) and, although the PRISMS trials (which used SC IFNbeta-1a) found that weekly doses totaling 132 mcg were more effective than a 66-mcg dose, if you wish to stick to the interferon-beta-1a molecule, this approach may be a reasonable alternative. A less costly alternative is to switch to IFNbeta-1b, which offers a higher, more frequent weekly dose, with demonstrated clinical effectiveness.

Suggested Reading

Cohen JA, Goodman AD, Heidenreich FR, et al. Results of IMPACT, a phase 3 trial of interferon beta-1a in secondary progressive multiple sclerosis. Neurology. 2001;56(suppl):A148. Abstract S20.003.

Coyle PK. Results of comparative efficacy trial using two formulations of interferon beta-1a in RRMS. Program and abstracts of the 17th World Congress of Neurology; June 17-22, 2001; London, UK. J Neurol Sci. 2001;187(suppl 1):S436. Abstract 66.04.

Durelli L, Ferrero B, Ghezzi A, et al. The Independent Comparison of Interferon (INCOMIN) Trial: A Multicenter Randomized Trial Comparing Clinical and MRI Efficacy of IFN Beta-1a and Beta-1b in Multiple Sclerosis. Neurology. 2001;56 (suppl):A148. Abstract S20.001.

Martin R, Sturzebecher CS, McFarland HF. Immunotherapy of multiple sclerosis: where are we? Where should we go? Nat Immunol. 2001;2:785-788.

Sorensen PS, Ross C, Koch-Hendriksen N, et al. Immunogenicity of interferon (IFN)-beta in MS patients. Influence of IFN-beta preparation, dosage, dose frequency, and route of administration. Neurology. 2000;54(suppl):A233. Abstract S38.004.

The PRISMS Study Group and the University of British Columbia MS/MRI Analysis Group PRISMS-4: Long-term efficacy of interferon-beta-1a in relapsing MS. Neurology. 2001;56:1628-1636.