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

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
• neuropathies
• anti-MAG antibody neuropathy
• multiple sclerosis

Article highlights

• BTK orchestrate pivotal signaling pathways involved in immune-mediated neuroinflammatory disorders

• BTK inhibitor are under investigation in different immune-mediated neuroinflammatory diseases

• Several BTK inhibitor exists with different safety profiles

• The availability of more selective BTKi, with less adverse events, will expand our treatment landscape

Declaration of interest

Andrea Visentin participated to scientific boards organized by Janssen, Astrazeneca, Abbvie, and Beigene.

Chiara Briani received speaker and consulting honoraria from Alnylam, Ionis, and Pfizer, and travel grants from Kedrion, Alnylam, and CSL Behring.

Marco Puthenparampil received travel grants and speaker honoraria from Novartis, Sanofi Genzyme, Biogen, Merk Serono, Almirall, Teva, Roche, Janssen, and Alexion; he has been consultant for Sanofi Genzyme, Novartis, Bristol-Meyer Squibb, Janssen, and Biogen. He is Principal Investigator of two trails (Roche, NCT04586010, and Sanofi Genzyme, NCT04458051) using BTKi in multiple sclerosis.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Authors contribution

AV, MP, CB conceive, wrote and revised the review.

Acknowledgments

Chiara Briani is a member of the European Reference Network for Neuromuscular Diseases.

Additional information

Funding

This paper was not funded.