Patricia K. Coyle, MD: The EXPAND study was the phase 3 trial in secondary progressive MS [multiple sclerosis] that validated siponimod, a second-generation S1P [sphingosine 1-phosphate] receptor modulator, an oral agent, versus placebo. What they looked at in this study was active secondary progressive MS, those who had had a relapse in the prior 2 years or had a contrast enhancing lesion on their entry MRI [magnetic resonance imaging] scan because that was the ultimate approval, for active secondary progressive MS. Here they were looking at duration of MS. They broke it down into those who were less than 16 years into their disease process and those that were 16 years or longer into their MS process. This is important because in general the longer you're in the MS stage, the less well you respond to treatment because you've had that much more time to develop permanent injury damage to the central nervous system. 
 
They looked at confirmed disability progression at 3 months and at 6 months—3 months had been the primary outcome and 6 months was a secondary outcome. What they saw were in the patients with active secondary progressive MS, patients under 16 years in disease duration, they had significantly fewer going onto confirmed disability progression either 3 months or 6 months with siponimod versus placebo, even more dramatic changes than in the entire trial. They saw a trend, a clear trend in favor of less progression at 3 months and 6 months in those who had the disease duration greater than 16 years, but it did not reach statistical significance. However, they had fewer patients in the study. So is that an element of fewer patients statistically, or was it that they had longer disease? Obviously, we can't rule out that that was a factor. But still there was a clear trend in less confirmed progression in the siponimod versus the placebo group. 
 
The real-world significance of this study is that we can say that even if you’ve had very long-standing MS and you’re active secondary progressive, I think the expectation is that you're going to get a benefit from siponimod treatment. It's somewhat arguing to treat as early as possible. You saw even better progression disability lowering in the active secondary progressive MS cohort, so it's certainly an encouraging feature to talk about this as a valid therapy for these patients.