Ocrelizumab for Relapsing MS

Matthew J. Baker, MD: What’s been your take on other high-efficacy medications like B-cell depleting therapies such as ocrelizumab? I know there was some data presented at ACTRIMS [The Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2020] looking at the open-label extension study and 6-year data on relapse rate and disability progression.

Jeffrey M. Kaplan, MD: Yeah, there was a good poster there by Dr Stephen Hauser on long-term reduction of relapse rate and confirmed disability progression after 6 years of ocrelizumab treatment in patients with relapsing MS [multiple sclerosis]. As we know, there were 2 extremely important studies done for ocrelizumab: OPERA I (NCT01247324) and OPERA II (NCT01412333). And that was a double-blind placebo period. Then there was a 3-year follow-up study, for a total of 6 years of treatment.

They took the patients who were previously randomized to ocrelizumab and they continued them on ocrelizumab. Or, they took the patients previously randomized to interferon β-1a and switched them to ocrelizumab. And then they looked at the annualized relapse rates, time to exposure, confirmed disability progression, and change of the adjusted mean EDSS [Expanded Disability Status Scale]. And basically, the results showed a favorable outcome.

Their conclusions were that after 6 years of follow-up, a proportion of patients have lower relapse rates and improved disability outcomes with ocrelizumab. Also, there was a benefit shown in the patients who were on ocrelizumab for 6 years versus those who were switched at 3 years. So I will kind of directly quote them here: Switching from interferon to ocrelizumab after 2 years at the start of the open-label extension period was associated with a reduction of annualized relapse rate.

And then, both the ocrelizumab to ocrelizumab portion of the trial and the [patients with] interferon to ocrelizumab maintained their reductions in annualized relapse rates through the 4-year follow-up of this open-label period. So to me, the significance of this data is that here we have a medication that, as I spoke of earlier, is more of a high-efficacy medication and shows it clearly works better than a lower-efficacy but higher-safety medication such as interferon. And this is always heartening to me, because I’m on the induction side.

Now I’m going to reverse the course here a little bit. In my anecdotal experience, I personally have not found ocrelizumab to be as effective as I have seen it be in the trials, especially in my primary-progressive patients. They did receive an indication for that. And when I look back at the initial primary-progressive study, some of those patients had T1 [Gadolinium]-enhancing lesions. Some of those patients had relapses. So I really felt like a significant portion of the patients they were calling primary-progressive actually would fall into what we would now call active secondary-progressive multiple sclerosis. I think this is what led to the statistical significant difference in the patients taking ocrelizumab versus the patients taking the placebo, and the primary-progressive…What are your thoughts?

Matthew J. Baker, MD: Yeah, I tend to agree with that. I think the data in the primary-progressive trial was driven greatly by those patients who had inflammatory disease. In the real-world setting, in my practice, the patient I have who has primary-progressive MS has been followed for 10, 15, 20 years now. And now, this a medicine that’s approved for primary-progressive MS, and they may have a very low burden of disease in the brain and significant burden of disease in the spinal cord. And there’s no evidence of active enhancing lesions. So I think the expectation of the medication is to prevent or delay further disability progression.

I’m dealing with an older patient population with longer duration of disease but with less active MRI findings. And so, yeah, I would tend to agree with that. But like I think with any of the therapy, early identification, early initiation of effective therapy, which is what the 6-year data showed—getting someone on effective therapy early on, at least in the relapsing forms—is critical. This is probably also true for primary-progressive MS.

I tend to be more of a lumper. I think MS is MS is MS, and I think the progressive nature of it might be driven by more spinal cord involvement or other host factors and genetic factors.