Do you feel comfortable combining mycophenolate mofetil with azathioprine in patients with lupus?

Aggressive immunosuppression is occasionally indicated for patients with lupus. Examples include refractory lupus nephritis, lupus with secondary CAPS, refractory immune-mediated cytopenia, etc. Treatment options often consist of high-dose steroids with at least one other immunosuppressive agent. Additionally, we often use multi-targeted or combination treatments consisting of two or more immunomodulatory drugs beyond glucocorticoids. The original NIH PACIV trial demonstrating cyclophosphamide is superior to prednisone alone in the management of lupus nephritis included an arm with both oral cyclophosphamide combined with azathioprine. Currently, combinations include MMF plus tacrolimus, MMF plus voclosporin, MMF plus belimumab, MMF plus ri...

I have not ever used that combination that I remember but certainly have had patients on mycophenolate and tacrolimus, mycophenolate and benlytsa, and mycophenolate and saphnelo. Obviously would need close follow-up regarding blood counts etc. I have also used mycophenolate along with methotrexate and leflunomide depending on their current disease activity and symptoms. We have all experienced patients with renal disease responding to one agent, but their arthritis or skin disease remains active.

It would be great to have a bit more information about the clinical presentation for which this combination is being considered, but I could not think of a scenario where I would consider combining MMF and Aza. In addition to the standard approaches with MMF and Belimumab or MMF/CNIs (that I would use not just for nephritis but for lung disease or myositis), I've successfully combined MMF with Abatacept for arthritis. MMF and Rituximab could be combined, but I tend to do this for vasculitis or refractory myositis, not lupus. I would also consider anifrolumab for non-renal disease. Cyclophosphamide is still an option in severe cases.