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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
Arthritis Research & Therapy volume 4, Article number: 113 (2002)
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.
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.
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.
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.
This case provides histopathological documentation of a significant treatment benefit from anti-CD20 plus cyclophos-phamide in a patient refractory to cyclophosphamide alone.
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van Vollenhoven, R., Gunnarsson, I., Welin-Henriksson, E. et al. 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. Arthritis Res Ther 4, 113 (2002) doi:10.1186/ar449
- Lupus Nephritis
- Proliferative Lupus Nephritis
- Investigational Treatment
- Chronicity Index