Bruton tyrosine kinase inhibitors: can they be optimized for the treatment of neuroinflammatory disorders?

Expert Opin Investig Drugs. 2023 Jul-Dec;32(12):1105-1111. doi: 10.1080/13543784.2023.2288076. Epub 2023 Dec 28.

Abstract

Introduction: Bruton's tyrosine kinase (BTK) is a multifaceted player of the immune system which has been involved in the survival of hematological malignancies but also in the pathogenesis of immune-mediated diseases. Oral BTK inhibitors (BTKi) have become a cornerstone for the treatment of patients with B-cell malignancies, and are under investigation for several immune-mediated diseases.

Areas covered: We reviewed the biology of BTK and emerging data on BTKi in patients with neuroinflammatory disorders of both the peripheral and central nervous system.

Expert opinion: We support the use of BTKi in relapsed/refractory patients with multiple sclerosis and anti-MAG antibody neuropathies. However, other immune-mediated neuroinflammatory disorders are likely to benefit from BTKi. Whether BTKi will improve the response rates than conventional therapies in previously untreated patients is unknown and will be assessed within future clinical trials. Furthermore, the availability of more selective BTKi, with less adverse events, will improve patients' tolerability and expand our treatment landscape.

Keywords: BTK; BTK inhibitors; anti-MAG antibody neuropathy; multiple sclerosis; neuropathies.

Publication types

  • Review

MeSH terms

  • Agammaglobulinaemia Tyrosine Kinase
  • Hematologic Neoplasms* / drug therapy
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell* / drug therapy
  • Neuroinflammatory Diseases
  • Protein Kinase Inhibitors / adverse effects
  • Tyrosine Kinase Inhibitors

Substances

  • Tyrosine Kinase Inhibitors
  • Agammaglobulinaemia Tyrosine Kinase
  • Protein Kinase Inhibitors