CMSC Data Release: Abstract DXT58 and MS Risk Reduction

Xavier Montalban, MD, PhD: I would like to discuss the paper on the reduction of the risk of secondary progressive multiple sclerosis [MS] in patients who were treated with cladribine in the CLARITY study. As you know very well, cladribine is an oral medication for multiple sclerosis. Cladribine selectively depletes lymphocytes, and it has a minimal effect on the immune cells.

In the CLARITY study, quite a large number of patients were studied—433 were treated with cladribine, and 437 were treated with placebo. All these patients had relapsing-remitting multiple sclerosis. The progression to secondary progressive MS [SPMS] was not a defined outcome of the trial.

This paper for the CMSC [Consortium of Multiple Sclerosis Centers] 2020 annual meeting, they used a number of combinations between confirmed disability for progression, and also confirmed progression of functional systems, mainly pyramidal, I guess to define a sort of secondary progressive MS. It’s like a proxy of SPMS.

Overall, to be brief, the proxy SPMS progression was seen in 6.7% of cladribine-treated patients, versus 13.5% in patients who had placebo. It’s quite a difference, in a statistical and significant way.

Then if we split the patients into 2 groups, those with a baseline EDSS [Expanded Disability Status Scale score] of 3 or lower, and those who had an EDSS at baseline of 3.5 or higher, the difference are still there. Just to give you some numbers, in patients with a baseline EDSS of 3 or lower, proxy SPMS progression occurred in 3.5% versus 7.7% in the placebo group.

And in patients with a baseline EDSS of 3.5 or higher, the numbers are 12.2% in patients who had cladribine versus 22.4% in patients who had placebo. You can see that difference between patients treated with cladribine versus placebo in relation to this proxy SPMS concept, or outcome. Also if we look to patients who reached an EDSS of 6, which is quite a high disability, the difference was there.

I think in conclusion, the risks of progressing to SPMS, using a proxywithin 2 years of treatment for relapsing-remitting MS, cladribine versus placebo, are significantly reduced in comparison to placebo. And this is independent from the baseline EDSS, which I think is positive data, and it’s a good piece of information that, again, transmits to our patients.

The question here is always the same. We are now using anti-inflammatory drugs to treat patients with relapsed-remitting MS. Only 1 drug has been approved for the treatment of SPMS, and only 1 drug has been approved for general primary progressive MS.

I think it will be very difficult to run an SPMS trial in many of these drugs. So it’s very nice to analyze in a different way the data we already have, and identify if there is any signal of efficacy in reducing the percentage of patients who develop SPMS. I think that’s the main message coming from this study.