Prospect of Bruton’s tyrosine kinase inhibition as an upstream therapeutic approach in myasthenia gravis

Myasthenia gravis (MG) is a rare autoimmune neuromuscular disorder characterised by fluctuating muscle weakness and fatigue resulting from autoantibody- or complement-mediated disruption of neuromuscular junction function. Although current therapies, including immunosuppressants, complement inhibitors, neonatal Fc receptor antagonists and B-cell-depleting agents can offer meaningful disease control, some patients continue to experience fluctuating or enduring symptoms, delayed treatment effect, tolerability challenges or barriers in administration. Bruton’s tyrosine kinase (BTK), a cytoplasmic tyrosine kinase involved in B-cell receptor signalling and innate immune cell activation, is a potential therapeutic target for autoimmune conditions, implicated upstream of many pathogenic processes. BTK inhibition may offer a novel approach to modulate both adaptive and innate immune responses in MG pathophysiology, with the potential to reduce downstream autoantibody production, antigen presentation and pro-inflammatory cytokine release. These mechanisms could be relevant across MG serotypes. Early data from other immune-mediated diseases suggest that BTK inhibitors, such as remibrutinib, may have favourable pharmacokinetic and safety profiles, and could offer flexible oral dosing and reversible immune modulation. In contrast to B-cell-depleting therapies, BTK inhibition may allow for transient modulation of immune activity without sustained immunosuppression in MG, which could be advantageous in long-term disease management. Safety and lifestyle considerations, including infection risk, hepatotoxicity and implications for reproductive health, remain important, and emerging data suggest that some BTK inhibitors may be well tolerated. Although clinical experience of BTK inhibition in MG is limited, a phase III clinical trial is taking place to determine whether BTK inhibition is a meaningful therapeutic option. If efficacy and a manageable safety profile are confirmed, targeting the underlying mechanisms of disease with BTK inhibitors could provide a valuable addition to the treatment landscape, particularly for patients with diverse serotypes and unmet clinical needs.