Immunoglobulins in Primary Progressive and Relapsing-Remitting Multiple Sclerosis

Jason Freeman, MD, MBA: Welcome to ACTRIMS 2023. I'm your host, Dr Jason Freeman, Medical Director, Novartis Medical Affairs, providing you updates from ACTRIMS 2023. The information herein is provided for disease educational purposes only, and is not intended to be, nor does it imply medical or diagnostic advice. Joining us today from ACTRIMS is Dr Shankar Sadasivan, a Medical Science Liaison with Novartis Pharmaceuticals. Welcome, Shankar.

Shankar Sadasivan, PhD: Thank you, Jason.

Jason Freeman, MD, MBA: So, we're going to discuss one of the posters that you covered while you were here at ACTRIMS that really focused on immunoglobulins especially IgG and IgM in patients both with primary progressive as well as relapsing remitting MS [multiple sclerosis]. So, before we get into the poster, tell us a little bit about what immunoglobulins are and why they matter, especially for patients on anti-CD20 therapies.

Shankar Sadasivan, PhD: So, immunoglobulins are proteins that are secreted into the blood, and the source of these immunoglobulins are B-cells. So, with anti-CD20s, as you mentioned, the therapies that are approved in MS, these therapies, they deplete these B-cells, which are the source of immunoglobulins. Now, what has been shown in science is that IgG particularly has been associated with long-term immunity. Now, as MS patients are at a higher risk for infections, if you, that, there is a potential that if you deplete the B-cells, you have a potential of reducing these immunoglobulin G levels, which could potentially alter the infection risk for patients with MS.

Jason Freeman, MD, MBA: So just the takeaways there, they're part of our immune system.

Shankar Sadasivan, PhD: Yes.

Jason Freeman, MD, MBA: They're an important part of how we protect our bodies from infections.

Shankar Sadasivan, PhD: Yes.

Jason Freeman, MD, MBA: And viruses and that sort of thing. And the therapies that we're going to talk about in particular affect them.

Shankar Sadasivan, PhD: Yes.

Jason Freeman, MD, MBA: So, Shankar, talk to us about anti-CD20 therapies available for the treatment of multiple sclerosis.

Shankar Sadasivan, PhD: So right now, as of today, there are 3 monoclonal antibodies that are approved to treat relapsing forms of MS. These are all anti-CD20 proteins that target the CD20 epitope. So, these B-cells have CD20 it's like a lock and key mechanism. So, they have the lock and the CD20 protein, which are approved therapies, they are the key. And once they form that lock and key, they target these B-cell towards cell death.

Jason Freeman, MD, MBA: And so again, that lock and key, they lock together, and then they have the potential to deplete those B-cells, which could then affect our IgG and IgM. So, in terms of this particular study, what are some of the outcomes that were examined?

Shankar Sadasivan, PhD: So, in this study, they looked at 2 cohorts. So, one was a patient cohort where they were experiencing primary progressive MS [PPMS]. The other one was a relapsing remitting MS [RRMS] patient cohort. So, this is what, this was a retrospective chart review study. And each of these patient cohorts, they were on an anti-CD20 therapy for at least 3 years. So, the primary outcome that they measured in this particular study was whether there were abnormalities associated with primary progressive MS patients or relapsing MS patients based on their IgG or IgM levels. So, what was found in this particular study was that patients who have been diagnosed with primary progressive MS and on an anti-CD20 therapy for at least 3 years, they have abnormal, they have a potential to have abnormal IgG, IgM levels compared to patients who are relapsing remitting MS patients on an anti-CD20 therapy.

Jason Freeman, MD, MBA: And this was the same across the therapy selected.

Shankar Sadasivan, PhD: So, this particular study was out of British Columbia in Canada. And so, they were the primary progressive patients were treated with a different anti-CD20 therapy while the relapsing remitting MS patients were treated on a different anti-CD20 therapy. It was based on what was available for treatment or approved for treatment in Canada. And it's not a US-based study, it's a Canadian study. So, the treatment paradigms are a little bit different.

Jason Freeman, MD, MBA: So, can you discuss the different levels of IgG and IgM in these patients either with PPMS or RRMS? And what are the clinical implications of the results?

Shankar Sadasivan, PhD: So as mentioned earlier, PPMS patients on anti-CD20 therapy did see abnormal levels of, when I say abnormal levels, it can be wherein patients had reduced IgG, IgM levels in PPMS versus patients on RRMS. They didn't see as much fluctuation in their IgG, IgM levels. What was also interesting was a secondary outcome in the study, which showed that BMI numbers did not necessarily affect how these immunoglobulin levels fluctuated.

Jason Freeman, MD, MBA: And so, in terms of our clinical takeaways and what this means for patients what, what do you want to share with our audience?

Shankar Sadasivan, PhD: So, this is a small cohort that was studied patient cohort that was studied. So, the clinical takeaways were patients with PPMS could experience these abnormal fluctuations in IgG, IgM levels, and as we had discussed previously, there is a potential for these fluctuations to translate into the risk of infections. So, it's not clear yet, this particular study does not go into that into that area of exploration, but there is a potential for these PPMS patients on anti-CD20 therapies for longer periods of time could potentially experience more infections because of these immunoglobulin fluctuations.

Jason Freeman, MD, MBA: And that's distinguished then from RRMS where, essentially, they might be a little bit safer in terms of their ability or risk of future infections related to anti-CD20s.

Shankar Sadasivan, PhD: As I said, the study does not go into that. But there is, you can potentially extrapolate that because of the stability or the lack of abnormal levels of immunoglobulin experienced in relapsing remitting MS patient population.

Jason Freeman, MD, MBA: Sure. And that, I mean, with more and more patients being put on these therapies, that's really important information. So, thanks for sharing that with us.

Shankar Sadasivan, PhD: Absolutely. And RRMS patient cohort was also the average age was 45 versus the PPMS patients who were 55, age of 55. So again, the younger, you target the younger patient population that you target with anti-CD20 therapies, the potentially better prognosis you get.

Jason Freeman, MD, MBA: Thanks for your time today, Shankar. We appreciate you sharing this information with us.

Shankar Sadasivan, PhD: Absolutely, my pleasure.

Jason Freeman, MD, MBA: Thank you for watching the ACTRIMS 2023 updates sponsored by Novartis. We look forward to seeing you at AAN 2023 for more exciting updates.

Transcript Edited for Clarity