Open-Label Extension: Phase 3 OPERA I and II Trials in Relapsing MS

Mark Freedman, MD: The last abstract was from the virtual American Academy of Neurology Annual Meeting, where long-term data were now being analyzed from patients who were in OPERA I and OPERA II. Those are the 2 relapsing, remitting trials comparing ocrelizumab with subcutaneous interferon-beta-1A [INFBR1A]. In those studies, patients moved over after the 2 years from the interferon to the ocrelizumab arm. In the open-label extension of both these studies, patients were followed and examined at regular intervals. This particular report suggests that after 6 years the patients who reached confirmed disability progression were small in number. But no one knows what the natural history is, so all we can say is those patients who were in the study and took ocrelizumab, especially took it at the beginning rather than crossed over from the interferon arm, seemed to have lower overall progression rates at year 6 compared with those who delayed treatment with the ocrelizumab and were assigned to the interferon arm initially.

We are not told about the dropout rates and who dropped out of each group. The overall scheme is just that if you stayed in the study, chances are you were probably doing well. The implication is that probably more patients dropped out of the interferon arm, because they were unlikely to have done well. But we have no real comparator here in terms of the natural history of this group that we could rely on, saying, yes, this is a significant effect, and this would not have happened by natural history alone, or that the patients who were randomized from the start on ocrelizumab are that much better.

But the data can be used to say that this is a higher-efficacy therapy. In terms of ocrelizumab, we know that. That’s what the 2 OPERA studies showed. Moving on to a higher-efficacy therapy from the beginning seems to indicate that that would be the best outcome in the long term, and this is quite intuitive today. Other large studies have also intimated the same, that higher-efficacy therapies from the outset tend to have the best long-term prognosis.