Successful treatment of refractory lupus nephritis by the sequential use of rituximab and belimumab

The ideal therapeutic approach for lupus nephritis (LN) is to quickly achieve a complete remission and maintain that response long-term while minimizing drug toxicity, and prevent tissue damage and death. The combination therapy consisting of multiple medications is aimed at incorporating drugs with complementary actions at reduced doses to achieve additive or synergistic therapeutic effects while minimizing toxicity. Here, we review the available evidence using combination therapies (triple therapy) and how such strategies can improve therapeutic efficacy in LN, which will mainly focus on the combination of high-dose corticosteroids with mycophenolate mofetil (MMF) and a calcineurin inhibitor (CNI) at low dose. We discuss the rationale, efficacy, and safety of the therapy, as well as its molecular mechanisms. We also discuss the questions raised from the trials and briefly describe emerging approaches developed on the basis of combination therapy, and these advances that promise to improve on the standard-of-care treatments and toward individual therapy in LN.