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EAN 2023 | Updates on BTK inhibitor safety in multiple sclerosis

Bruce Cree, MD, PhD, MAS, from University of California, San Francisco, CA, discusses recent developments in Bruton’s tyrosine kinase (BTK) inhibitors as promising therapeutics for multiple sclerosis (MS). There is excitement about BTK inhibitors because of their ability to cross the blood-brain-barrier to tackle compartmentalized inflammation and neurodegeneration, which could directly slow disease progression in MS. They may also have alternative roles beyond their action on B-cells, including targeting microglia. However, the GEMINI 2 study (NCT04410991), examining the BTK inhibitor tolebrutinib as a treatment for relapsing MS, has uncovered safety concerns related to drug-induced liver injury, leading to the cessation of recruitment in the US. Other BTK inhibitors such as evobrutinib have raised similar issues and add to the concern that this may be a class effect of these inhibitors. Remibrutinib is the most promising BTK inhibitor currently in early development, as it has been investigated as a treatment for another autoimmune condition where no drug related liver injuries were observed.
Recorded at the 9th Congress of the European Academy of Neurology (EAN) 2023 held in Budapest, Hungary.

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Bruce Cree reports the following disclosures: I have received personal compensation for consulting from Alexion, Atara, Autobahn, Avotres, Biogen, Boston Pharma, EMD Serono, Gossamer Bio, Hexal/Sandoz, Horizon, Immunic AG, Neuron23, Novartis, Sanofi, Siemens and TG Therapeutics and UCSF has received research support from Genentech.