Biopsy-verified response of severe lupus nephritis to rituximab (anti-CD20 monoclonal antibody) plus cyclophosphamide after biopsy-documented failure to respond to NIH-protocol cyclophosphamide

Background

The monoclonal anti-CD20 antibody rituximab (Rituxin, Mabthera) is approved for the treatment of certain B-cell lymphomas. Because of its ability to deplete B lymphocytes the drug may be of benefit in antibody-driven diseases. While treatment of proliferative lupus nephritis with cyclophosphamide-based therapies is succesful in most SLE patients, some have persistently active disease despite such treatment; we currently employ an investigational protocol for the use of rituximab in such patients.

Case report

A female patient with SLE since age 20 underwent renal biopsy at age 31 because of urinary abnormalities. Iohexol clearance at that time was 55 ml/min. She was otherwise asymptomatic. The renal histology showed focal proliferative glomeru-lonephritis, WHO IIIB, activity index 6/24, chronicity index 6/12. Immunofluorescence revealed 3+ IgG, IgM, and complement in the glomeruli. The patient was given cyclosphophamide and corticos-teroids according to the usual NIH protocol for six months. A repeat biopsy after these 6 treatments revealed no improvement, the activity and chronicity scores being largely unchanged. Subsequently, the patient enrolled in the rituximab investigational treatment program.

Treatment

The patient was given 4 weekly infusions with 375 mg/m2 rituximab as well as cyclophosphamide 500 mg/m2 × 2 plus methylprednisolone 1000 mg along with the first and fourth anti-CD20 infusions. Oral prednisolone was maintained at 5 mg/day.

Results

The patient tolerated the treatment well with only minor infusion-related side effects. Clinically she remained asymptomatic. Repeat kidney biopsy 3 months after completion of rituximab treatment revealed SLE nephritis WHO class IB with minimal residual activity (activity index 1/24), and chronicity index 6/12. Immune fluorescence revealed only minimal deposits. Iohexol clearance remains stable at 55 ml/min.

Conclusion

This case provides histopathological documentation of a significant treatment benefit from anti-CD20 plus cyclophos-phamide in a patient refractory to cyclophosphamide alone.