Is combination rituximab with cyclophosphamide better than rituximab alone in the treatment of lupus nephritis?
OBJECTIVE
To assess if combination rituximab and cyclophosphamide is more effective than rituximab monotherapy as an induction therapy for proliferative lupus nephritis.


METHODS
A randomized open-label pilot study in which 9 patients received rituximab alone and 10 patients received two doses rituximab + intravenous cyclophosphamide. The clinical, laboratory and renal histological changes were assessed after 48 weeks of treatment.


RESULTS
At week 48, four patients had a complete response, 11 patients achieved partial response, 2 patients remained the same or stable and 2 worsened. There were no statistical differences in the proportion of patients with complete or partial response between the two groups. None of the variables was an independent predictor of response at week 48. Nine patients had significant improvement in activity indices in renal biopsies, but there were no significant differences between the two groups. Overall, 18 out of 19 patients were found to have effective B-cell depletion. The median duration of complete B-cell depletion in all patients was 22 weeks. There were no statistically significant differences in the proportion of patients with complete depletion at weeks 4, 8, 24 and 48 between the two groups except at week 2.


CONCLUSIONS
Rituximab monotherapy appears to be effective as induction therapy in lupus nephritis. The addition of cyclophosphamide offers no additional improvement in clinical, laboratory and renal histological assessment or the duration of B-cell depletion at 48 weeks. Large-scale studies with longer duration are needed to confirm these findings.
Li
Edmund K
EK
Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong. edmundli@cuhk.edu.hk
Tam
Lai-Shan
LS
Zhu
Tracy Y
TY
Li
Martin
M
Kwok
Catherine L
CL
Li
Tena K
TK
Leung
Ying Ying
YY
Wong
Kong Chiu
KC
Szeto
Cheuk Chun
CC
D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D001402:B-Lymphocytes / Q000276:immunology; D015415:Biomarkers / Q000652:urine; D016009:Chi-Square Distribution; D003404:Creatinine / Q000652:urine; D003520:Cyclophosphamide / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008181:Lupus Nephritis / Q000188:drug therapy* / Q000276:immunology / Q000652:urine; D018655:Lymphocyte Count; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use; D008875:Middle Aged; D012074:Remission Induction; D000069283:Rituximab; D018709:Statistics, Nonparametric; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D015415:Biomarkers; D007166:Immunosuppressive Agents; D000069283:Rituximab; D003520:Cyclophosphamide; D003404:Creatinine; D008775:Methylprednisolone