Bruton's tyrosine kinase inhibitors: a new class of multiple sclerosis therapeutics

Bruton's tyrosine kinase (BTK) is an intracellular enzyme involved in a wide range of cellular functions. BTK inhibitors (BTKIs) are of interest in multiple sclerosis because they modulate various types of immune cells that have key roles in multiple sclerosis pathophysiological processes, including B cells and microglia. Moreover, because BTKIs are small molecules that might cross the blood-brain barrier and potentially modulate relevant cells within the CNS, there is added interest in their use in multiple sclerosis. In the past decade, there has been a flurry of drug development of BTKIs in multiple sclerosis. The BTKIs being evaluated in multiple sclerosis have differences in pharmacological properties that might result in meaningful differences in safety and efficacy. Recently reported phase 2 and phase 3 clinical trials have provided the field with renewed hope that some BTKIs could modulate progressive multiple sclerosis disease mechanisms that current disease-modifying treatments insufficiently address. However, meaningful differences in clinical outcomes and MRI findings have been reported. If the beneficial findings seen with some BTKIs are confirmed, these observations suggest the beginning of a new era of treatment in multiple sclerosis. The results of upcoming clinical trials, real-world studies, and regulatory approval decisions will guide a more nuanced approach to determining the patient populations that will benefit most from this treatment class.