Patricia K. Coyle, MD: There were 2 interesting presentations on the CLARITY trial. CLARITY was the pivotal phase 3 trial for relapsing multiple sclerosis where they looked at oral cladribine in 2 different doses—3.5 mg/kg and 5.25 mg/kg—compared to placebo. In the first study they looked at 2 very important markers, the first being transition from relapsing to secondary progressive MS [multiple sclerosis]. They had worked out some parameters that made that very likely. The second was transition to a well-documented disability marker, EDSS [Expanded Disability Status Scale] 6, where you need to use a unilateral cane to get around. They broke down the groups by lower EDSS, EDSS 3 or less or EDSS 3.5 or less, and they focused on the 3.5 mg/kg cladribine dosing group—which is the proven dose—and the placebo arm. Indeed, statistically significantly fewer patients, less than half as many, transitioned to secondary progressive MS with cladribine treatment versus placebo, whether their EDSS scores were low or high. In addition, significantly fewer went on to reach EDSS 6, that bad disability marker.
I think transition to secondary progressive MS is something we really want to prevent from happening because it means inevitable disability, so I thought that was very reassuring. In addition, they also looked at the cohort that had received the 3.5 mg/kg cladribine dose in the 2 years of the pivotal CLARITY trial, and then they went into an extension period. Some of those patients received a whole second course of oral cladribine, whereas another group did not, they received placebo. They looked at time to first relapse, and what they found was that there was no difference between the 2 groups. In other words, the cladribine, which is a very durable induction or immune reconstitution strategy, kept its benefit in years 3 and 4 without further treatment. There was no added benefit to getting the extra cladribine doses, so it really confirmed the label approval, and it confirmed the durability of taking this oral agent—it has a long-lasting effect.
The significance of this data for the real world is that we have a hard parameter decreasing relapsing to secondary progressive MS. We want to be able to tell our patients that the treatment, the expectation is that it can do that, and the EDSS 6 is a very pragmatic hard marker. The patient needs an assistive device to walk. That's significantly less likely to occur on treatment. It's very reassuring to discuss those very practical take-home lessons for our patients with MS. This is the expectation that the treatment will hopefully prevent this from happening.