Optimal Management of Relapsing Multiple Sclerosis: Advanced Practice Providers Perspectives - Episode 10

Anti-CD20 Therapies for Relapsing MS

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An overview of clinical trial data supporting the use of ocrelizumab and ofatumumab as treatment options for patients with relapsing multiple sclerosis.


Stephanie Agrella, PhD, APN-BC: Sure. We’ve made some progress for certain. There was a time not that long ago when there were questions as to whether B cells were even involved in MS [multiple sclerosis]. Fortunately, we’ve successfully seen that targeting B cells with our patients with MS and using these monoclonal antibodies that specifically target CD20, we’ve been able to establish that it’s not a question any longer whether the B cells contribute, but it’s more related to how do they contribute to disease activity? And fortunately, we have studies that have demonstrated that the treatments we have here effectively deplete the circulating B cells and are fairly well tolerated. And while they do come with their own set of risks, the results have demonstrated a substantial reduction in that new MS disease activity.

When looking at our first anti-CD20, ocrelizumab, we’re specifically referring to that humanized anti-CD20 that specifically targets the CD20 marker on B lymphocytes and depletes them. Not only is this therapy the first that we’ve had as an option for our patients with primary progressive disease, as we found out from the ORATORIO study, but it’s also an option for patients with relapsing MS based on the studies OPERA 1 and 2, which as you all know, these are 2 identical trials and they compared IV [intravenous] ocrelizumab to subcutaneous interferon beta-1a at 44 μg, 3 times a week. The results from that particular trial found that ocrelizumab was associated with lower rates of disease activity and progression versus the interferon. This was an active comparator study. The relative reductions that we saw in annualized relapse rates were in the range of 46%, 47% compared to interferon. And those treated with ocrelizumab we also saw that they had significant reductions in their confirmed disability progression at 3 and 6 months. When we looked at their MRI, impressively we saw that those treated with ocrelizumab had near complete suppression of those Gad-enhancing lesions.

The study also found some other interesting things, and this is a first that I can think of, and you guys correct me if I’m wrong, but this is the first study where I can recall that improvements were noted. And what I mean by that is they found that 33% more patients on ocrelizumab showed an improvement on their EDSS [Expanded Disability Status Scale], and they were able to confirm that in 3 months compared to those on interferons. That’s something we haven’t seen in previous studies, and not only is the efficacy there, we’re starting to make progress toward some improvements with that. It really wasn’t that long ago that we only had the injectables and IV options, and so of course, with that we had the ASSESS study for fingolimod, that first S1P that Bryan mentioned earlier. And as you all recall, from that trial what we saw was that fingolimod was compared at 2 different strengths, 0.25 and 0.5 mg, versus glatiramer acetate at 20 mg subq [subcutaneous] in patients with relapsing-remitting MS. And those results found that the treatment with 0.5 mg reduced the annualized relapse rate by 41%. It was this study that solidified the first oral options for our patients living with relapsing MS, as Bryan mentioned earlier.

Getting back into the anti-CD20s, our most recent option for our patients with relapsing MS is ofatumumab. As you all know, again, it’s a fully humanized monoclonal, it selectively depletes B cells. The difference here of course is that instead of it being intravenous, it’s subcutaneous. It was studied in the ASCLEPIOS trial, which again, had an active comparator, assigning patients to either subcutaneous ofatumumab or teriflunomide. What we found from this particular trial was that greater than 50% fewer relapses were detected in those who were treated with OFA [ofatumumab]. And subjects were also 34% less likely to have disability progression, and again we saw good data on their MRI, somewhere between 94% and 98% fewer Gad-enhancing lesions if they were treated with ofatumumab versus teriflunomide. Within the last 10 years or so, we’ve added oral therapies as an option, and now we have effective anti-CD20 therapies, one IV, one subcutaneous. While these options do have their own sets of risks, all of the data that we can see from the trials have demonstrated a substantial reduction in that disease activity. It’s just another treatment option that we can offer to our patients.

Amy Perrin Ross, APN, MSN, CNRN, MSCN:Thank you all so much. I would like to thank this wonderful panel, Christen Kutz, Stephanie Agrella, Bryan Walker, and Patricia Melville for this wonderful discussion. I’d like to thank you, as an audience, for watching NeurologyLive® Peer Exchange. If you enjoyed the content, I suggest that you subscribe to the NeurologyLive® newsletters to receive information about upcoming Peer Exchange segments and other content available to you. Thank you all so much.

Transcript edited for clarity.