BTK Inhibitors Show Promise in MS, but Questions Remain

Clinical trials of novel Bruton tyrosine kinase (BTK) inhibitors in patients with relapsing-remitting multiple sclerosis (MS) and progressive MS are yielding encouraging results, according to a review published in JAMA Neurology.

“BTK is centrally involved in the B cell receptor–mediated activation of B cells, one key requirement in the development of autoreactive B cells, but also in the activation of myeloid cells, such as macrophages and microglia,” wrote experts from University Medical Center in Göttingen, Germany.

Compounds currently in development vary in aspects such as binding mode, inhibitory concentration, and selectivity and specificity, the article explained. They also differ in their potential to enter the central nervous system, likely an important factor since inflammatory circuits in the brain are believed to drive MS progression.

Questions yet to be answered are the long-term effect of using BTK inhibitors, since a continuous lack of B cells may cause a drop in the endogenous production of immunoglobulins and pose other safety risks, and where BTK inhibitors should fall within the realm of MS therapeutics.

“A comparative analysis of their distinct properties is necessary to identify which inhibitors may be used in relapsing vs progressive forms of MS as well as to clarify which agent may be most suitable for sequential use after anti-CD20 treatment,” the authors advised.

Reference:
Dybowski S, Torke S, Weber MS. Targeting B cells and microglia in multiple sclerosis with bruton tyrosine kinase inhibitors: a review. JAMA Neurol. Published online February 13, 2023. doi:10.1001/jamaneurol.2022.5332