Rituximab use as induction therapy for lupus nephritis: a systematic review

Objective Rituximab (RTX) has important usage in rheumatoid arthritis and vasculitis. There remains a need for more, better, and safer treatments for patients with lupus nephritis (LN). RTX has been trialed in such patients without definitive conclusions about its effectiveness. As a role for RTX has not been clearly established for LN, we carried out a systematic review and analysis. Methods We identified 31 studies of RTX for class I-VI LN, and assessed complete renal response (CRR) and partial renal response (PRR) using criteria including serum creatinine, proteinuria, and urinary sediment. Due to differences in the pediatric presentation of the disease, studies focusing on pediatric patients were excluded. Results One randomized controlled trial (RCT) showed superiority of RTX+cyclophosphamide (CYC) versus CYC alone (64% vs. 21% CRR and 19% vs. 36% PRR). Six prospective and retrospective studies utilizing RTX monotherapy found 66% CRR or PRR in all patients. Eleven studies that investigated RTX in combination with CYC or mycophenolate mofetil (MMF) also found 66% CRR or PRR in all patients. In total, the CRR for Caucasian, East Asian, and Hispanic patients were 77%, 38%, and 28%, respectively. Conclusions RTX appeared to benefit certain LN patients, but most studies were not randomized or properly controlled, were heterogeneous in design, subjects, and LN types, and were not comparable, and must therefore be interpreted cautiously. RTX alone may not deplete B cells sufficiently for the perturbations of LN. In addition, RTX may induce responses differently among patients of different ethnic and racial backgrounds. Furthermore, there were wide variations in the baseline characteristics of the patients, namely LN class, time course of disease, age, and prior immunosuppressive use. We suggest a prospective RCT in patients aged 18-65 years with class IV LN. Ideally, the patients would not have received prior immunosuppression and would better represent different ethnicities. The treatment groups would be RTX, RTX+belimumab, CYC, and MMF groups, with pulse-dose steroids during induction followed by maintenance steroids and MMF. The CRR and PRR would be assessed at 12 and 24 months. This or a similar study might clarify RTX's role in the treatment of LN.