Would you consider adding voclosporin to belimumab and MMF in the setting of active proteinuria, rather than switching agents?

I would first answer the question whether the proteinuria is due to active lupus nephritis (LN) or not and whether this can be addressed by adding/increasing the dose of an ACEi/ARB.

For active LN, I would switch to Voclosporin from Belimumab (continuing MMF) primarily because of concerns for toxicity. Combining all three immunosuppressive medications (Belimumab+MMF+Voclosporin) is something that warrants evaluation. I would also consider Cyclophosphamide in this situation depending on the patient's characteristics.

Agree with my colleagues. Sometimes, persistent proteinuria could arise from secondary FSGS or lupus podocytopathy. These scenarios may be refractory to immunosuppression. Before escalating immunosuppression like Cyclophosphamide have a low threshold to repeat the renal biopsy to make sure active Class III, IV , V or TIN is what going on.

AS THE EXCEPTION AND NOT THE RULE, I have added voclosporin to the care of multi-system lupus patients who were actively treated with belimumab and MMF in biopsy-proven WHO IV GN. (Both failed the European protocol of cyclophosphamide). Both responded to this combination. I began a taper of belimumab in one patient who evolved a cutaneous flare; apparently, her immune system thinks all three are necessary.

These patients are challenging but if watched closely can be managed in this manner. This is definitely off-label.