Clyde E. Markowitz, MD: The EXPAND trial, which was a secondary-progressive multiple sclerosis [MS] clinical trial, was really asking the question, “If you have patients who have secondary-progressive disease, would a medication like siponimod make a difference?” What we found in the trial was that it hit on the end points of slowing the rate of disability progression, but the question was, “Is the secondary-progressive population more active?” More active could be having had relapses in the last 2 years or MRI [magnetic resonance imaging] activity, etc. If that is the population we’re going to study, and you ask the question, “Does disease duration play into that?” they broke it out into if patients had disease duration less than 16 years or more than 16 years. 
 
They were able to show that the population that was active with disease duration less than 16 years had a more robust effect on slowing the rate of disability progression both in the 3- and 6-month time points, somewhere in the range of 35% to 40%. That was compared with people who had a longer disease duration, greater than 16 years, which also was quite impressive but maybe not as robust—in the 24% to 30% range—in slowing the disability progression. 
 
To me, the way I view that is in your population of patients who are earlier in the course of secondary-progressive disease, you’re going to have a more robust effect than waiting for them later in the disease. It’s important to identify those patients as early as possible and get them on treatment as early as possible. 
 
In the clinical practice of MS, it’s really important for us to be able to identify which patients are in that category of progression. Right now, it’s really difficult for us to find a defined point to say, “You are now in secondary-progressive disease.” It’s very slow and indolent. I think we have to start asking these questions, something we were not able to do previously in part because we didn’t really have any treatments that would be able to address the secondary-progressive population, but now we do. We have data now even from a study like this that show the earlier you identify these patients, you may have a greater effect. This becomes very practical to us, being able to figure out how to identify them and asking the questions about progression in the early secondary-progressive setting.