Fred Lublin, MD: Does this not provide us an opportunity to think about de-escalation when you’re thinking about what to go to next and the individuals who have done very well?
Wallace Brownlee, MBChB, PhD, FRACP: That’s right, Fred. There are a couple of groups of patients who are particularly attractive to treat with cladribine. One is perhaps the patients who are more treatment experienced, older, or have a higher EDSS [Expanded Disability Status Scale] score. This medicine may be a nice exit strategy from disease-modifying treatment [DMT] without the concerns that you have with other agents about inducing rebound or severe disease reactivation when medication is stopped. Another particularly attractive group of patients to treat is young women, as we’ve heard already. We have an increasing number of treatment options that facilitate family planning, but this is a particularly good option in that women are able to fall pregnant 18 months after starting the therapy if they complete both courses of treatment and then wait 6 months. Then they’re free to start trying for a baby.
Fred Lublin, MD: Patricia, the Europeans were ahead of us on this one and have more experience, but I’d love to hear your thoughts about cladribine.
Patricia K. Coyle, MD: It’s very interesting. We’re looking in the United States at what exactly is the role for cladribine. It has a fairly high efficacy agent, higher than the other orals, maybe a step below the monoclonal antibodies, and it is an induction immune reconstitution agent. As noted, it is very appealing to work pregnancy around that, very appealing to people who like the idea of taking short courses and having a prolonged drug-free period. There were some very respected MS [multiple sclerosis] neurologists who used parenteral cladribine off-label over the years. They would re-dose periodically, and they felt that this was very successful. To me, the most unsteady, disconcerting thing is this, “Treat for the specific 2 courses, and then don’t treat again.” We have to come to some resolution, so I’m hoping that we get valuable data from Europe to guide us since they’re about a year and a half ahead of us.
Wallace Brownlee, MBChB, PhD, FRACP: We all feel comfortable though, Patricia, in patients treated with alemtuzumab just to monitor patients because we know from the long-term follow-up of the CARE-MS I, CARE-MS II study, this treatment paradigm of giving short-course pulse immune reconstitution therapy can bring about a lasting remission for a good proportion of people, at least for alemtuzumab, and perhaps for cladribine also.
Patricia K. Coyle, MD: Absolutely. You have some data for alemtuzumab, but do you have that data for cladribine?
Wallace Brownlee, MBChB, PhD, FRACP: No, and that’s what we need to collect.
Patricia K. Coyle, MD: Yes.
Fred Lublin, MD: You’re using cladribine in the first line in Europe?
Wallace Brownlee, MBChB, PhD, FRACP: Yes, that’s right. At our center, the National Hospital for Neurology and Neurosurgery, it’s roughly half of patients we treat. It’s patients who are first line, generally those with more active MS as described earlier: 2 relapses in the previous 12 months. And then the other half of patients are people who’ve had ongoing disease activity on a previous treatment. It’s interesting to note that, in the United Kingdom now, cladribine is the number 1 medicine for first switches, so people switching from their first DMT to another therapy, cladribine is now the front-runner in that particular race.
Fred Lublin, MD: Interesting. In the United States, there was a relabeling of the drugs that occurred after the siponimod approval, where all the disease-modifying therapies for relapsing disease were re-labeled to include clinically isolated syndrome [CIS], relapsing-remitting MS, and secondary progressive MS with activity. We can come back to the issues with that labeling characterization, of which there are quite a few, later. But cladribine, which had a study in clinically isolated syndrome, which many of the others did not, was excluded from including clinically isolated syndrome in their label, as was alemtuzumab. Any thoughts on that, Patricia?
Patricia K. Coyle, MD: It doesn’t make sense that cladribine, which had what looked like a very positive CIS trial, was excluded. It was excluded strictly because they’re saying we’re concerned about malignancy issues, but it got approved in the United States because they weren’t so concerned about malignancy issues. This was on scheduled to be the first approved oral agent, and it wasn’t. It wound up ultimately getting approved because it didn’t overtly cause major cancer concerns, so it is quite puzzling to me. It doesn’t make sense.
Fred Lublin, MD: On that safety concern, have any safety concerns arisen in Europe over the time you’ve been using it? Anything new?
Sven Meuth, MD, PhD: We have some patients, around 10%, reporting fatigue while they are taking the medication, which is a transient phenomenon, and we have some higher rates of herpes infections compared to the CLARITY trial, but this is basically it. There was 1 herpes encephalitis reported as maybe a major adverse effect, but this could also be treated with IV [intravenous] acyclovir treatment. So far, it is quite safe, I have to say.