Potential of BTK Inhibitors for Primary Progressive Multiple Sclerosis: Patricia K. Coyle, MD

WATCH TIME: 3 minutes

"If either of these studies are positive, you will now have a treatment that was penetrating into the [central nervous system] and able to show a benefit in progressive [multiple sclerosis], and I think you will see it widely used."

Although the disease pathology of primary progressive multiple sclerosis (MS) is still not fully understood by clinicians, studies have characterized the condition by compartmentalized inflammation and loss of axons behind a closed blood–brain barrier.¹ Before March 2017, there was no effective treatment for the condition despite the “arsenal” of therapies available for relapsing remitting forms of MS. Ocrelizumab (Ocrevus; Roche), the only FDA-approved treatment for primary progressive MS, led to lower rates of clinical and MRI progression compared with placebo in a previously completed phase 3 trial (NCT01194570).² Despite ocrelizumab’s approval, there remains a need for more effective treatment options.

An emerging therapy class in MS are the Bruton’s tyrosine kinase (BTK) inhibitors. BTK is expressed in B-cells and myeloid cells, which include key progenitors like dendritic cells, microglia, and macrophages. These cells are integral to MS pathogenesis, along with mast cells, making BTK inhibitors relevant to various autoimmune diseases. First-generation BTK inhibitors are currently being used to treat B-cell malignancies and have shown efficacy in modulating B-cells. Prior studies have also shown B-cell depleting therapies were successful as disease-modifying treatments for MS, indicating the potential of BTK inhibitors for treating primary progressive MS and other forms of the disease.³

Patricia K. Coyle, MD, a professor of neurology at Stony Brook Medicine, recently presented on the diagnosis, clinical course, and management of primary progressive MS in a session at the 2024 Consortium of Multiple Sclerosis Centers (CMSC) Annual Meeting, held May 29 to June 1, in Nashville, Tennessee. After the meeting, Coyle sat down in an interview with NeurologyLive^® to discuss the specific targets of the new therapy class of BTK inhibitors being tested for primary progressive MS. She talked about how the current trials compare BTK inhibitors with existing approved treatments like ocrelizumab. Furthermore, she spoke about the potential impact of early intervention in the silent period of primary progressive MS.

Click here for more coverage of CMSC 2024.

REFERENCES
1. Ontaneda D, Thompson AJ, Fox RJ, Cohen JA. Progressive multiple sclerosis: prospects for disease therapy, repair, and restoration of function. Lancet. 2017;389(10076):1357-1366. doi:10.1016/S0140-6736(16)31320-4
2. Montalban X, Hauser SL, Kappos L, et al. Ocrelizumab versus Placebo in Primary Progressive Multiple Sclerosis. N Engl J Med. 2017;376(3):209-220. doi:10.1056/NEJMoa1606468
3. Airas L, Bermel RA, Chitnis T, Hartung HP, Nakahara J, Stuve O, Williams MJ, Kieseier BC, Wiendl H. A review of Bruton's tyrosine kinase inhibitors in multiple sclerosis. Ther Adv Neurol Disord. 2024 Apr 17;17:17562864241233041. doi: 10.1177/17562864241233041. PMID: 38638671; PMCID: PMC11025433.030056