Lancet Neurol: Is the oral brain penetrating BTK inhibitor tolebrtinib safe and effective in the treatment of relapsing multiple sclerosis?

Multiple sclerosis is an immune- mediated inflammatory demyelinating disease that causes loss of axons, neurological disease, and cumulative disability
.

Immunomodulatory treatment can lead to an annual recurrence rate as low as 0.

Immunity because existing treatments mainly affect peripheral adaptive immunity

Bruton tyrosine kinase is a non-receptor tyrosine kinase that is expressed in most hematopoietic cells (excluding T cells and fully differentiated plasma cells) and connects specific cell surface receptors to downstream signaling pathways , Which links immune stimulation with cell activation

Tolebritinib is an oral small molecule that irreversibly binds to Bruton's tyrosine kinase and inhibits its activity

The researchers conducted a 16-week phase 2b randomized, double-blind, placebo-controlled, cross-dose discovery trial in 40 centers (academic sites, specialist clinics, and general neurology centers) in 10 countries in Europe and North America
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Eligible participants are adults aged 18-55 who have been diagnosed with relapsing multiple sclerosis (relapsing-remitting or relapsing secondary progressive multiple sclerosis) and meet one or more of the following Criteria: at least one relapse in the past year, at least two relapses in the past two years, or at least one active gadolinium-enhancing brain injury within 6 months before screening

Phase 2b randomized, double-blind, placebo-controlled, cross-dose discovery test diagnostic screening

• From May 14, 2019 to January 2, 2020, a total of 130 participants were recruited and randomly assigned to take tolebrtinib: 33 to 5 mg, 32 to 15 mg, 33 to 30 mg and 32 to 60 mg
  .
  
  129 cases (99%) completed the treatment plan, and 126 cases entered the preliminary analysis
  
  After 12 weeks of tolebrtinib treatment, new gadolinium-enhanced lesions were reduced in a dose-dependent manner, and the 60 mg dose was the most effective, and the drug was well tolerated
  
  Literature source: Reich DS, Arnold DL, Vermersch P, et al.
  Safety and efficacy of tolebrutinib, an oral brain-penetrant BTK inhibitor, in relapsing multiple sclerosis: a phase 2b, randomised, double-blind, placebo-controlled trial.
  Lancet Neurol.
  2021;20(9):729-738.
  doi:10.
  1016/S1474-4422(21)00237-4 Reich DS, Arnold DL, Vermersch P, et al.
  Safety and efficacy of tolebrutinib, an oral brain-penetrant BTK inhibitor, in relapsing multiple sclerosis: a phase 2b, randomised, double-blind, placebo-controlled trial.
  Lancet Neurol.
  2021;20(9):729-738.
  doi:10.
  1016/S1474-4422(21)00237-4 in This message