ACTRIMS 2020 News Network: Updated Data From the CLARITY Study

Clyde E. Markowitz, MD: The CLARITY trial was an interesting study. It was performed over a decade ago. We are now looking at those data again because cladribine got approved last year in 2019. What is interesting is that the study was designed as a relapsing-remitting multiple sclerosis trial. It was not designed as a secondary-progressive multiple sclerosis trial. In clinical trials these days, you can actually come up with surrogate markers that could be used as markers of patients with secondary-progressive disease. That could include a certain level of EDSS [Expanded Disability Status Scale]. So you can use maybe an EDSS score greater than 3 or 3.5 with a functional score of at least 2 on the pyramidal, or you could use an EDSS score of 6, which requires somebody to use a cane. Those are defined metrics that you could actually use to make the determination: Is the patient in the trial hitting those milestones?

As part of the design of the study, patients are followed by their EDSS scores. If they were at a score less than 3, you would have a baseline score, and then you could measure them over time. If they increase their disability progression, you could say they hit a milestone of greater than 3.5, confirmed for greater than 3 or 6 months. They would have met that disability progression. You could have people who had an EDSS score greater than 4 who might progress up to an EDSS score of 6, and you could actually look at these metrics and use those as proxies for secondary-progressive disease.

In the trial, they looked at this and actually found about a 50% reduction in patients who were treated with oral cladribine compared with the placebo group of those metrics of going by these proxies to hit this secondary-progressive end point. Overall it gives us comfort to say that a medication like this can reduce the risk to go on to develop secondary-progressive disease.

In the real world, you’re going to ask the question: If I put my patient on this medication, am I going to be able to prevent them from hitting the secondary-progressive proxy end points that we just talked about? The reality is yes, you might actually have this as a very comfortable place to think, “I have somebody who’s maybe on the edge of that conversation, who’s maybe starting to have some ambulatory difficulty. If I start them on this medication at this point, I might actually have an impact in the long term hitting those secondary-progressive metrics.”

What’s interesting about the CLARITY trial and how the drug is administered is that it’s a very short course of treatment. You’re really using it for 5 days, then the next month for another 5 days, and the following year you use it for 5 days, and follow in the next month with another 5 days. Then you’re essentially done with the treatment. They’re short courses of treatment, and you’re asking the question: How good and long term is the benefit? If you follow these patients—and that’s what they did in the extension trial—they looked to see what proportion of patients was relapse-free and how patients did in the long term. Is it maintained?

What was nice is at least from the standpoint of looking at the relapse metrics, there were data to suggest that it is maintained over time. If you were concerned that somebody was going to have a relapse in a short amount of time and the medication may not be very effective at 2, 3, or 4 years, these data would suggest that it’s maintained throughout the entire period of that extension, so that you can feel comfortable putting your patients on a treatment like this and it’s going to have a durable effect that’s going to last for much longer than the duration of the treatment itself.