Experts in the field of multiple sclerosis discuss patient selection for drugs based on disease activity.
Bruce Cree, MD: I’m now going to ask the panel a question about the selection of patients. Bob and Kristen provided excellent summaries of the clinical trials. They’ve highlighted a couple of features, which I believe are commonly shared for both studies. Younger patients who have evidence of disease activity, ie, either gadolinium-enhancing lesions at baseline for both studies, or a recent history of relapses for the secondary progressive MS [multiple sclerosis] clinical trial, meaning relapses within 2 years prior to entry into the study, tended to do quite well on these therapies.
I’ll open this up to panel discussion, but I’m going to ask Joe first. How do you select these treatments for your patients with SPMS [secondary progressive multiple sclerosis] and PPMS [primary progressive multiple sclerosis], knowing that some of them have disease activity and others simply don’t?
Joseph R. Berger, MD: It’s an extremely difficult question to answer. I tend to default in my patients with primary progressive MS, particularly those who are younger. We certainly see people in their late 70s and 80s when they first present, and I’m not sure about the wisdom of starting them on any medication.
But with younger patients, I generally default to ocrelizumab because the data were generated for PPMS with ocrelizumab. As I mentioned earlier, I can’t say that I’m bowled over by the effects of the drug. Sometimes it’s extremely difficult to determine what effect you’re having on the course of the illness because every patient is so unique.
Since we are able to use anti-CD20 antibodies, at least in the United States, and the mechanism of action is similar in the patients with PPMS as in the SPMS group, I often, not invariably, default to an anti-CD20 with patients who have SPMS. I’ll occasionally use an S1P [sphingosine-1-phosphate modulator], depending on what the patient is interested in. There are a fair number of patients who simply don’t get treated. They get treated symptomatically, and I don’t feel as if there’s a particular therapy that’s going to be particularly helpful for them.
That’s generally what I do, but I depend as much on the patient preferences, which we’ll talk about a little later. There are some patients who come in and insist on being treated. In some instances, I’ve tried both drugs sequentially. When one doesn’t appear to be working, I try another.
Bruce Cree, MD: Bob, I’m going to pick on you to follow up on this idea that Joe just mentioned about sequential therapy. Do you do sequential therapy between these products? If so, how do you select which one to begin with? What kind of patient do you begin it in?
Robert Fox, MD: There are 2 main things that I’m now wrestling with in the middle of a pandemic, and hopefully we will be in a post-pandemic period soon. We know that older patients have a decreased benefit from these therapies and may have an increased risk of complications. Keep in mind that the siponimod secondary progressive trial enrolled no one over than the age of 50, and the ocrelizumab primary progressive trial enrolled no one over the age of 55.
We don’t know what the risk-benefit trade-off is in patients who are older than those ages. We have lots of patients, as Joe alluded to, who are over age 60 with primary and secondary progressive MS, and we don’t have trial data to guide us. I am worried that the risk-benefit trade-off may not be positive for patients who don’t have evidence of active inflammation and do have risks of complications from these rather strong immune-modulating therapies. Adding to that, we know the response to vaccines is decreased in patients treated with anti-CD20s, and with S1P modulators.
We would expect that the response to, for example, a COVID-19 vaccine will be diminished. We know that the complications of COVID-19 in anti-CD20–treated patients are higher than the complications of COVID-19 in the patients not treated with anti-CD20 antibodies.
We’re now getting a better sense of balancing the risks and benefits, and realizing that there are some risks, risks of other complications and of insufficient response to a vaccine. That has made me quite cautious before I put a patient, particularly those aged over the mid-50s to 60, without evidence of active inflammation, on these drugs.
In terms of sequential therapy, it’s a little tricky. I’m more comfortable going from an S1P, which washes out quickly, to an anti-CD20. It’s a little bit hard to know when the anti-CD20 is no longer effective, and I don’t have the potential additive complication risk of an anti-CD20 plus an S1P modulator. That makes it much more complicated to go from an anti-CD20 to S1P than the reverse.
Bruce Cree, MD: You touched upon an excellent point, which has to do with safety considerations with the potential for sequential therapy use.
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Transcript Edited for Clarity