title: Efficacy and safety of rituximab in children with difficult-to-treat nephrotic syndrome.
abstract: BACKGROUND
  Rituximab has emerged as an important medication for patients with steroid-dependent or steroid-resistant nephrotic syndrome.
  
  
  METHODS
  We report the efficacy and safety of therapy with intravenous rituximab, administered once weekly for 2-4 doses, in 193 patients (mean age 10.9, range 2.2-18.7 years) with difficult-to-treat steroid dependence (n = 101), calcineurin inhibitor (CNI)-dependent steroid resistance (n = 34) and CNI-resistant nephrotic syndrome (n = 58) managed at this center during 2006-13.
  
  
  RESULTS
  Therapy in patients with steroid dependence and CNI-dependent steroid resistance led to significantly reduced relapse rates (respective mean difference 2.7 relapses/year and 2.2 relapses/year, corresponding to a decrease in relapses by 81.8 and 71.0%; both P < 0.0001). This resulted in a significant reduction in steroid requirement (mean difference 104.5 and 113.6 mg/kg/year, respectively; both P < 0.0001) and a trend to improved standard deviation scores for height (P = 0.069) and body mass index (P = 0.029). Remission was longer in patients with steroid dependence compared with CNI-dependent steroid resistance (median 16 versus 10 months; P < 0.0001). Prior response to cyclophosphamide predicted a lower risk of relapse in the former (hazard ratio, HR 0.56; P = 0.045); patients with initial resistance and CNI-dependent steroid resistance had increased risk of relapse (HR 2.66; P = 0.042). B-cell recovery, noted in 62.5% patients at 6 months, was not related to occurrence of relapse; redosing (n = 42 patients) was safe and effective. Response to therapy was unsatisfactory in patients with steroid- and CNI-resistant nephrotic syndrome, with remission in 29.3%. Focal segmental glomerulosclerosis was associated with higher odds of non-response (odds ratio 11.1; P = 0.028) and lack of response was associated with progressive chronic kidney disease (HR 9.97; P = 0.035). Therapy with rituximab was safe; adverse effects or infections were noted in 19 (9.8%) patients.
  
  
  CONCLUSIONS
  Therapy with rituximab is effective and safe in reducing relapse rates and need for immunosuppressive medications in patients with steroid-dependent and CNI-dependent steroid-resistant nephrotic syndrome.
authors.affiliation: Division of Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Aditi
authors.initials: A
authors.lastname: Sinha
authors.affiliation: Division of Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Divya
authors.initials: D
authors.lastname: Bhatia
authors.affiliation: Division of Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Ashima
authors.initials: A
authors.lastname: Gulati
authors.affiliation: Division of Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Rawat
authors.affiliation: Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Amit K
authors.initials: AK
authors.lastname: Dinda
authors.affiliation: Division of Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Hari
authors.affiliation: Division of Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Arvind
authors.initials: A
authors.lastname: Bagga
mesh_terms: D000293:Adolescent; D000328:Adult; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D004351:Drug Resistance / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009404:Nephrotic Syndrome / Q000188:drug therapy* / Q000401:mortality; D016017:Odds Ratio; D011379:Prognosis; D012008:Recurrence; D012074:Remission Induction; D000069283:Rituximab; D012449:Safety; D016879:Salvage Therapy; D015996:Survival Rate; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D000069283:Rituximab
keywords: B-cell depletion; calcineurin inhibitors; focal segmental glomerulosclerosis; steroid resistance; steroid-dependent nephrotic syndrome