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Steroid Dependent Nephrotic Syndrome (SDNS) and Frequent Relapse Nephrotic Syndrome (FRNS) management could involve a severe degree of steroid toxicity. Rituximab (RTX), an anti-CD20 monoclonal antibody, appears to have beneficial effects in these groups of patients.
Patients with primary SDNS or FRNS in relapse after 12 months of Mycophenolate Mofetil (MMF) or 3 months of Cyclophosphamide (CFM) or 12 months of Levamisole.
Treatment: 4 doses of RTX 375mg/m2/weekly or 2 doses of 750mg/m2/biweekly (maximum 500mg/dose), and monthly dosage of CD20 for 1 year.
Definitions:
CD20 depletion: CD20 lymphocyte count <1% of total B cells or <5 cells/mm3.
CD20 cell recovery: CD20 cell count in peripheral blood > 1%.
Inclusion criteria:
Age between 5 and 11 years; glomerular filtration rate greater than 90ml/min/1.73m2; complete vaccination for pneumococcus and meningococcus
Exclusion and interruption criteria:
Active infectious and/or tumor processes; immunodeficiency; leukopenia (<3000/mm3); neutropenia (<1500/mm3); thrombocytopenia (<50,000/mm3); refractory anemia; persistent gastrointestinal intolerance; reduction in creatinine clearence >30% from baseline for more than 3 months; established sensitivity to the drug; patients who did not attend 2 or more consecutive appointments for control.
Study duration: 24 months.
TREATMENT:
10 patients with SDNS in remission while receiving MPD (mean dose 20 mg/m2/alternate days) received RTX 375 mg/m2/dose weekly for 4 doses.
10 patients were admitted (7 girls, 3 boys), average age 11.5 years. Prior to the RTX infusion all of them received MPD, 8 MMF, 1 levamisole and 1 CFM.
Six patients remained in remission post-RTX for 12 months. The mean time to first relapse was 114.3 days. Post-RTX patients presented an average of 2 relapses each, remitted with MPD in all cases, 1 patient was assumed to be corticosteroid resistant until being removed from the study to receive CsA.
The incidence of relapses in patients with FRNS during the year before RTX infusion was 4/patient/year and 0.8/patient/year (p 0.001) in the year after.
The CDS pre RTX was 4765 mg/m2 and the CDS post RTX was 2455 mg/m2 (p 0.001).
There was no significant difference in CD20 recovery: 149±33 and 131±72 days, between patients who remained in remission and those who had relapses post-RTX. The adverse effects were urticarial rash during the time of infusion and 2 patients with arthralgias and myalgias 24 hours after RTX, subsiding with analgesia.
In patients with SDNS and FRNS, Rituximab showed effectiveness in reducing the number of relapses and the total cumulative dose of steroids.