Cite as: Otten N. Comparison of drug treatments for multiple sclerosis. Ottawa: Canadian Coordinating Office for Health Technology Assessment (CCOHTA); 1998.
This rapid assessment brings together the major studies involving the four drugs available in various countries for the treatment of MS: Avonex® (interferon beta 1-a), Rebif® (interferon beta 1-a), Betaseron® (interferon beta 1-b), and Copaxone® (glatiramer acetate or copolymer 1) (Tables 1 and 2). Although these drugs are priced similarly, clinical trial methodology (in particular inclusion criteria, outcome measures, and doses used) have been sufficiently different that definitive conclusions as to their comparability cannot be made.
This review focuses on the major trials used to support market claims of their usefulness. Table 1 outlines the study parameters, while Table 2 provides the major results of each trial. Particular emphasis has been placed on Rebif® since this is the newest agent available. Comments and inferences regarding the various interferon preparations (e.g.: side effects, route of administration, etc.) are outlined which may be helpful when comparing these products. Important points pertaining to the methodology and/or interpretation of the results of major trials are highlighted and a section is devoted to some economic issues.
- All of the products now appear to have evidence that they impact the progression of the disease. However variations in endpoints, definition of endpoints, patient characteristics, and differences in doses (for the interferons) make any comparative evaluation difficult.
- Copaxone® (copolymer 1) possibly has a more profound effect early in the disease and may be more useful in relapsing-remitting MS with little accumulated neurological disability; i.e., possibly more useful early in the disease than later. However, further trials are required to substantiate this conclusion.
- The new trial results for Betaseron® (1-b) are only available in abstract form so critical analysis is difficult. However, the placebo group appeared to be more severe at baseline (13.1% vs. 18.6% of patients at EDSS of 3 to 3.5 while 47.2% vs. 42.5% at EDSS of 6.0 to 6.5) which may account for some of the increased proportion or placebo patients becoming wheel chair bound (seen when EDSS = 7.0).
- The impact on the rate of acute exacerbations seem to be similar among the different products (approximately 30% reduction). There is some evidence that there is a reduction of moderate and severe attacks. The cost-effectiveness of avoiding one acute exacerbation annually, mentioned in the CCOHTA report, would still be valid and is probably applicable to all the products. This value has been corroborated by an economic evaluation conducted in the UK.
- Regardless of the methodology used (cost/QALY as employed by Parkin et al or cost/EDSS disability years avoided used by Brown et al) these drugs are incrementally more expensive for the improvement expected than many interventions currently used in various health conditions.
Conclusions related to Rebif®
- The effect of Rebif® on progression was statistically significant, although there were wide confidence intervals indicating a wide variation in individual response. More importantly, the average change of 0.48 is not considered clinically significant.
- There is no statistically significant difference between the two doses used in the Rebif® trial (6 vs. 12 MIU). Since the differences in effect between the doses are not statistically significant, the higher premium for the 12 MIU dose (approximately $21,000) vs. 6 MIU (approximately $17,000) is probably not justified.
multiple sclerosis, interferon-beta, peptides, cost-benefit analysis, treatment outcome, drug therapy, beta-interferon, sclérose en plaques, MS, Economic, Interféron type I recombinant, Analyse coût bénéfice, Évaluation resultants traitement, Chimiothérapie, SEP, Interféron bêta-1b, Calcul des coûts