Lessons from randomised direct comparative trials

Anat Achiron*, Sten Fredrikson

*Corresponding author for this work

Research output: Contribution to journalEditorial


For over a decade, four immunomodulatory therapies have been available for the treatment of relapsing remitting multiple sclerosis. However, few direct comparative data were available to facilitate the choice of treatment. This choice has been influenced by the perception that interferon-β preparations have greater efficacy than glatiramer acetate, due to apparently more rapid and robust reduction of gadolinium-enhancing lesions seen on magnetic resonance imaging in the pivotal trials of these agents. This situation has changed in the last year, with the outcomes of three randomised clinical trials comparing the efficacy and safety of glatiramer acetate with that of a high-dose interferon-β in relapsing remitting multiple sclerosis. These are the REGARD, BEYOND and BECOME trials. In the REGARD trial, 764 patients were randomised to treatment with either interferon-β 1a sc 44 μg or glatiramer acetate for 96 weeks; no significant difference in the time to first relapse was observed. The largest of the three comparative studies, the BEYOND trial, compared treatment with interferon-β 1b sc 500 μg, interferon-β 1b sc 250 μg or glatiramer acetate for two years in 2,244 patients. The hazard ratio for multiple relapses was close to unity for comparisons between all groups, indicating equivalent efficacy in all three treatment arms. Relapse rates (around 0.3 relapses/year) in all these studies were much lower than anticipated and lower than those reported a decade previously in the pivotal trials of βb-interferons and glatiramer acetate. No unexpected safety issues were identified in any of these studies. The completion of these direct comparative studies has considerably enriched the clinical evidence database by contributing large numbers of patients. This provides an invaluable contribution for helping the physician make an informed choice about treatment. The results of the direct comparative studies provide evidence that glatiramer acetate and high-dose interferon-β preparations have comparable clinical efficacy.

Original languageEnglish
Pages (from-to)S19-S24
JournalJournal of the Neurological Sciences
Issue numberSUPPL. 1
StatePublished - 1 Feb 2009
Externally publishedYes


  • Evidence-based medicine
  • Glatiramer acetate
  • Interferon-beta
  • Multiple sclerosis
  • Randomised clinical trials


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