Treating Paramagnetic Rim Lesions in Multiple Sclerosis

Jemima Akinsanya, DO

The effects of anakinra (NCT04025554) and tolebrutinib on paramagnetic rim lesions (PRL) as seen on 7-Tesla magnetic resonance imaging (MRI) are being evaluated in 2 studies as part of a new phase 2a clinical trial paradigm for multiple sclerosis (MS).¹

The studies were presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum, February 25-27, by first author Jemima Akinsanya, DO, neuroimmunology clinical fellow, National Institutes of Health (NIH).

Anakinra is a recombinant human interleukin-1 receptor antagonist and was approved by the FDA for the treatment of rheumatoid arthritis and neonatal-onset multisystem inflammatory disease in 2001.² Tolebrutinib, meanwhile, is an investigational, orally available, brain-penetrant Bruton’s tyrosine kinase (BTK) inhibitor. NeurologyLive spoke with Akinsanya to learn more about how the 2 medications could improve patient care in MS. She also discussed further research she would like to see conducted with the treatments.

NeurologyLive: Can you provide an overview of these 2 studies you’re working on?

Jemima Akinsanya, DO: Yes. We are currently enrolling for the trial for the BTK inhibitor tolebrutinib. For anakinra, we've already started administering anakinra to patients in that trial.

So, anakinra is an injectable medication that the patients give to themselves daily, and we're doing MRIs to look and see if there's any modulation of the PRL, which you know, is the lesion that has both chronic and active inflammation components to it. And for the BTK inhibitor trial, with tolebrutinib, patients will take an oral medication daily. And, same thing, we're also going to be looking at MRI to see if there's any modulation of that PRL. So, both trials are looking to see if there's modulation of the PRL.

How could these medications help improve MS patient care?

The biggest thing that we are hoping for is to help with progression of disease. There are a lot of patients who have stable MRIs, but they have a progressive disease course clinically. And we really don't have good treatment options for these patients that don’t have enhancing lesions on their MRI for us to treat and like an acute flare that we can objectively identify. If there were new treatment options for these patients who are clinically worsening by, maybe progressively having difficulty walking, or progressive weakness, even though they're not having acute flares on their MRI, that would be a huge breakthrough for MS patients.

These medications are not yet approved for MS, I have to add. But, in terms of the mechanism, the fact that these medications are acting on microglia, is different than some of the other disease modifying therapies that are on the market right now.

What further research would you like to see in this area? 

I would love to see more research specifically looking at progressive MS it’s something very common when patients come in, and it's very disheartening as a clinician to not be able to provide more options for these patients. So, I'm excited to see what, down the line, could help. It's such a huge quality of life hindrance for patients, so to be able to provide them with treatments that can help slow the neuro degeneration and not just the acute inflammation would make a huge impact on them.

Transcript has been edited for clarity. For more coverage of ACTRIMS Forum 2021, click here.

REFERENCES

1. Akinsanya J, Absinta M, Dargah-zade N, et al. Toward the use of paramagnetic rim lesions in proof-of-concept clinical trials for treating chronic inflammation in multiple sclerosis. Presented at ACTRIMS Annual Forum; February 25-27, 2021. Poster P126.
2. Kineret® (anakinra) for injection, for subcutaneous use. FDA label. Updated December 2012. Accessed March 24, 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/103950s5136lbl.pdf