BACKGROUND: Subsequent to cyclophosphamide-based induction therapy of lupus nephritis, and despite maintenance chronic immunosuppressive treatment, many patients experience relapses. METHODS: This prospective, observational study included 10 women with biopsy-proven relapse of proliferative lupus nephritis occurring during maintenance with mycophenolate mofetil (MMF) or azathioprine. The long-term outcome after a single course of the B-cell depleting anti-CD20 antibody rituximab (4 weekly infusions of 375 mg/m(2)), combined with daily MMF (2 g) and prednisolone (0.5 mg/ kg/day for 4 weeks, tapered thereafter) is presented. RESULTS: While renal function was not severely impaired at baseline, partial remission (>50% improvement in all abnormal renal parameters) was achieved in eight patients at a median of 3.5 months. In seven patients, with 24-h urinary protein of 2.5 +/- 1.1 g (mean +/- SD), complete remission, associated with increases in serum complement levels and decreases in anti-dsDNA titres, was subsequently established (normal serum creatinine/albumin levels, inactive urine sediment and 24-h urinary protein <0.5 g). Complete nephritis remission was sustained at the follow-up end (median of 38 months) in six patients. Combination treatment was well tolerated. CONCLUSIONS: The efficacy of this low-toxicity combination was particularly evident in patients with subnephrotic proteinuria due to proliferative lupus nephritis relapse. Controlled trials to define the role of rituximab/MMF in this condition are warranted.
BACKGROUND: Subsequent to cyclophosphamide-based induction therapy of lupus nephritis, and despite maintenance chronic immunosuppressive treatment, many patients experience relapses. METHODS: This prospective, observational study included 10 women with biopsy-proven relapse of proliferative lupus nephritis occurring during maintenance with mycophenolate mofetil (MMF) or azathioprine. The long-term outcome after a single course of the B-cell depleting anti-CD20 antibody rituximab (4 weekly infusions of 375 mg/m(2)), combined with daily MMF (2 g) and prednisolone (0.5 mg/ kg/day for 4 weeks, tapered thereafter) is presented. RESULTS: While renal function was not severely impaired at baseline, partial remission (>50% improvement in all abnormal renal parameters) was achieved in eight patients at a median of 3.5 months. In seven patients, with 24-h urinary protein of 2.5 +/- 1.1 g (mean +/- SD), complete remission, associated with increases in serum complement levels and decreases in anti-dsDNA titres, was subsequently established (normal serum creatinine/albumin levels, inactive urine sediment and 24-h urinary protein <0.5 g). Complete nephritis remission was sustained at the follow-up end (median of 38 months) in six patients. Combination treatment was well tolerated. CONCLUSIONS: The efficacy of this low-toxicity combination was particularly evident in patients with subnephrotic proteinuria due to proliferative lupus nephritis relapse. Controlled trials to define the role of rituximab/MMF in this condition are warranted.
Authors: Namita T Gupta; Kristofor D Adams; Adrian W Briggs; Sonia C Timberlake; Francois Vigneault; Steven H Kleinstein Journal: J Immunol Date: 2017-02-08 Impact factor: 5.422