Combination strategies for lupus nephritis: facts and controversies

There is an unmet need to improve the efficacy of therapeutic regimens in lupus nephritis (LN). Cocktail immunosuppressive therapy for the synergistic effect of individual drugs may enhance efficacy and enable dosage reduction. However, the potential increase in the risk of serious and opportunistic infections is a concern. Moreover, the timing of combination therapy, adoption of a step-up or step-down approach, and the choice of drugs is still controversial, partly related to the cost-effectiveness issue.

Evidence of a combination of conventional, newer immunosuppressive, and biologic/targeted agents in LN.

Early combination of conventional regimens with anti-B cell activation factor (anti-BAFF) or calcineurin inhibitors (CNIs) enhances the therapeutic effect without increasing serious adverse events in LN. However, combining anti-CD20 and anti-BAFF biologics appears to be less promising from the results of clinical trials. Initial combination strategy may be more cost-effective for patients at risk of treatment failure and renal function deterioration. With the availability of more options, the treat-to-target approach in LN is increasingly feasible and further studies are needed to compare the step-up and step-down approaches in the treatment of LN.