Positioning Upstream and Downstream Therapies in MG

In ‘Positioning Upstream and Downstream Therapies in MG,’ our panel explores how FcRn inhibitors, complement inhibitors, and B-cell–directed approaches fit within the evolving treatment landscape. Expert faculty discuss the factors that may guide selection between the two established downstream classes, emphasizing antibody status, safety considerations, administration requirements, treatment frequency, and patient preference.

The panel notes that complement inhibition has a clear biologic rationale in appropriate acetylcholine receptor antibody–positive disease, whereas FcRn inhibition may be considered across a different range of antibody-defined populations. Safety considerations may also influence selection. The faculty specifically discuss the risk of meningococcal infection associated with complement inhibition and the resulting vaccination and prophylaxis considerations, which can affect patient willingness to initiate treatment.

Administration route and frequency are additional practical factors. The experts emphasize shared decision-making and the value of explaining these differences so that treatment can be aligned with individual preferences and lifestyle.

The conversation then shifts upstream to B-cell targeting. Panelists explain how CD20-directed therapy affects earlier portions of the B-cell lineage, whereas CD19 targeting extends further toward plasmablasts and short-lived plasma cells. However, currently available approaches may leave long-lived plasma cells intact, allowing continued or recurrent pathogenic autoantibody production. This limitation has contributed to interest in additional upstream strategies that interfere with plasma-cell development and B-cell survival.

Our next episode, ‘CD19 and CD20 B-Cell Depletion in MG,’ examines the evidence supporting inebilizumab and rituximab and how differences in B-cell targeting may translate into clinical practice.