New Insights into BTK Inhibitors and MRI Techniques for Smoldering MS: Thomas F. Scott, MD

WATCH TIME: 10 minutes

"We need to look at more nontraditional measures if we want to delve into the subject of smoldering [multiple sclerosis] and evaluate the potential role of [Bruton tyrosine kinase] inhibitors."

In the field of multiple sclerosis (MS), disability caused by the disease can derive from acute relapses or because of slow and steady deterioration. In the last decades, researchers have developed effective therapies to control the relapse activity in MS. These agents were primarily aimed to systemically target the peripheral immune system and/or prevent central nervous system (CNS) infiltration of immune cells.¹ One promising approach that may address the unmet need in patients may be inhibition of the enzyme Bruton's tyrosine kinase (BTK), which is centrally involved in the activation of B cells as well as myeloid cells.²

In a recent analysis of phase 2 studies assessing fenebrutinib (Roche), an oral investigational BTK inhibitor, results showed that the safety profile of the agent was similar in both patients with relapsing MS and other previously studied autoimmune indications. Presented at the 2024 American Academy of Neurology (AAN) Annual Meeting, held April 13-18, in Denver, Colorado, the data included 73 patients with relapsing MS and 577 patients with autoimmune indications who received fenebrutinib 200 mg BID across phase 2 studies.³ The previously studied indications included rheumatoid arthritis, systemic lupus erythematosus, chronic spontaneous urticaria.

Prior to the annual meeting, Thomas F. Scott, MD, director of the Allegheny Multiple Sclerosis Treatment Center at Allegheny General Hospital sat down with NeurologyLive® to discuss the potential impact of BTK inhibitors, such as fenebrutinib, on slowing the progression of MS. Scott, who also serves as professor and vice chairman of neurology at Drexel University College of Medicine, spoke about how the advancement of MRI techniques might aid in diagnosing and treating smoldering MS, a hot topic of conversation in the field. In addition, Scott talked about the challenges that may arise when using immune-suppressing drugs in older patients with MS.

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REFERENCES
1. Geladaris A, Torke S, Weber MS. Bruton's Tyrosine Kinase Inhibitors in Multiple Sclerosis: Pioneering the Path Towards Treatment of Progression?. CNS Drugs. 2022;36(10):1019-1030. doi:10.1007/s40263-022-00951-z
2. Elkjaer ML, Waede MR, Kingo C, Damsbo K, Illes Z. Expression of Bruton´s tyrosine kinase in different type of brain lesions of multiple sclerosis patients and during experimental demyelination. Front Immunol. 2023;14:1264128. Published 2023 Nov 13. doi:10.3389/fimmu.2023.1264128
3. Oh J, Raievska A, Sierzega M, et al. The Safety Profile of Fenebrutinib in Patients with Multiple Sclerosis Is Consistent with Those in Previously Studied Autoimmune Indications. Presented at: 2024 AAN Annual Meeting; April 13-18; Denver, CO.