Targeting CD19+  B Cells With Inebilizumab in Myasthenia Gravis

The MINT trial evaluated inebilizumab, a CD19-targeting monoclonal antibody, in both AChR-positive and MuSK-positive patients with myasthenia gravis, representing a novel upstream therapeutic approach targeting B-cell populations responsible for pathogenic antibody production. This therapy requires only 2 initial doses followed by maintenance dosing every 6 months, offering significant advantages in treatment burden reduction compared with more frequent administration schedules. The study uniquely incorporated corticosteroid tapering during the randomized controlled period, demonstrating continued efficacy while reducing prednisone from a maximum of
40 mg to 5 mg over 24 weeks.

Clinical results showed approximately 2-point improvements in MG-ADL scores for both AChR-positive and MuSK-positive patients, with additional benefits demonstrated on more objective quantitative myasthenia gravis assessments. The corticosteroid tapering success represents unprecedented achievement in myasthenia gravis clinical trials, as previous studies attempting steroid reduction failed to maintain clinical benefits. Some patients demonstrated treatment responses as early as 4 weeks, though maximal benefits appeared to increase with longer treatment duration between weeks 26 to 52.

The mechanism targeting CD19-positive B cells, including plasma blasts and plasma cells, may provide advantages over CD20-targeting approaches such as rituximab by addressing later stages of B-cell differentiation more directly involved in antibody production. The
6-month dosing interval potentially allows for combination therapies with other monoclonal antibodies without significant drug interaction concerns. Safety profiles appeared favorable, with placebo groups experiencing more adverse events than active treatment groups, suggesting good tolerability for this upstream targeting approach in myasthenia gravis management.