Jeffrey M. Kaplan, MD: So also, I was going to ask you about discussing the data that was released at the ACTRIMS 2020 meeting [The Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2020]. This is regarding time to first relapse after treatment with cladribine in the CLARITY study. I was wondering what your thoughts were on that?
Matthew J. Baker, MD: So you started the discussion off with our goals for MS [multiple sclerosis] therapy and introducing induction versus escalation therapy. And after I finish kind of giving my perspective on this, maybe you can chime in on whether or not you feel this is an induction therapy, as well. I think it is.
CLARITY [Cladribine Tablets Treating Multiple Sclerosis Orally (NCT00213135)] was a pivotal trial that evaluated oral cladribine versus placebo in the treatment of relapsing forms of MS. Patients were randomized to placebo or various dosages, 2 different doses, weight-based, of oral cladribine.
Those patients who were on placebo were then given the option to go on to the active drug. And then there was an extension trial (NCT00641537) for which patients treated with a 3.5 mg/kg option, after 2 years, could be randomized to either placebo or an additional dose of 3.5 mg/kg. And what this extension trial showed was that redosing really didn’t make a difference in the portion of patients who were relapse-free over 4 years.
So patients given the initial 3.5 mg/kg given in 2 cycles, each separated by a year, had a durable effect over a 4-year course, with respect to the proportion of patients who were relapse-free. So you started at about 90% at year 1, and then over the 4 years, it was around 70%. And there was no difference between those patients who received the additional dose after the first 2 years.
Jeffrey M. Kaplan, MD: I personally have been very fond of this, and I feel that it’s been a medication that has been very effective in the patients I have used it on. What are your thoughts about the concern of the black box warning and the possibility of increased malignancy with this medication?
Matthew J. Baker, MD: If it’s used within the labeling parameters that we have now, the risk is low. I also think it brings up an awareness of secondary malignancies in all of our MS patients on most of the newer disease-modifying therapies. Our immune system is there to protect us against infections. It’s also there to survey our normal cellular landscape for the evolution of potentially malignant cells.
So I think that if you look at the data, overall it’s in line with other registry data in MS patients not on therapy and with the normal populations. There didn’t seem to be a specific malignancy that emerged, so there wasn’t a trend toward 1 specific malignancy, which makes me feel more comfortable. But I do think it raises awareness in all of us that we have to counsel our patients to do their routine health care, routine cancer screens. That’s extremely important.
Jeffrey M. Kaplan, MD: I know there is a very good study out there that looks at the different rates of malignancies in all of the trials. There were definitely medications that had higher rates of malignancy than cladribine, but the placebo group was similar. So that red flag did not develop as it did when the CLARITY trial emerged. I think one of the most interesting things about the CLARITY trial was not so much the rate of malignancy in the treated group. Rather, it was the significantly low rate of malignancy in the placebo group.
Matthew J. Baker, MD: Right, that imbalance, yes.
Jeffrey M. Kaplan, MD: I think that’s what led to the imbalance that led to that black box warning. And so, I think that’s extremely important to know. There was a paper that showed the different rates of malignancies with different medications. It was very enlightening to me to review that and to realize this is an issue, to a degree, with all of our medications. But also, this gave me a piece of mind about the usage of cladribine.
Matthew J. Baker, MD: Right, absolutely.