Human or Chimeric Monoclonal Anti-CD20 Antibodies for Children with Nephrotic Syndrome: A Superiority Randomized Trial

J Am Soc Nephrol. 2021 Oct;32(10):2652-2663. doi: 10.1681/ASN.2021040561. Epub 2021 Sep 20.


Background: The chimeric anti-CD20 monoclonal antibody rituximab is effective in steroid-dependent and calcineurin inhibitor-dependent forms of nephrotic syndrome, but many patients relapse at 1 year. Because ofatumumab, a fully human anti-CD20 monoclonal antibody, has a more extended binding site and higher affinity to CD20 compared with rituximab, it might offer superior efficacy in these patients.

Methods: We designed a single-center randomized clinical trial to compare the long-term efficacy of ofatumumab versus rituximab in children and young adults with nephrotic syndrome maintained in remission with prednisone and calcineurin inhibitors. We randomized 140 children and young adults (aged 2-24 years) to receive intravenous ofatumumab (1.50 mg/1.73 m2) or rituximab (375 mg/m2). After infusions, oral drugs were tapered and withdrawn within 60 days. The primary outcome was relapse at 1 year, which was analyzed following the intent-to-treat principle. The secondary endpoint was relapse within 24 months from infusion, on the basis of urine dipstick and confirmed by a urine protein-to-creatinine ratio <200.

Results: At 12 months, 37 of 70 (53%) participants who received ofatumumab experienced relapse versus 36 of 70 (51%) who received rituximab (odds ratio [OR], 1.06; 95% confidence interval [95% CI], 0.55 to 2.06). At 24 months, 53 of 70 (76%) participants who received ofatumumab experienced relapse, versus 46 of 70 (66%) who received rituximab (OR, 1.6; 95% CI, 0.8 to 3.3). The two groups exhibited comparable B cell subpopulation reconstitution and did not differ in adverse events.

Conclusions: A single dose of ofatumumab was not superior to a single dose of rituximab in maintaining remission in children with steroid-dependent and calcineurin inhibitor-dependent nephrotic syndrome.

Clinical trial registration numbers: (NCT02394119) and (2015-000624-28).

Keywords: antirituximab antibodies; calcineurin inhibitor-dependent nephrotic syndrome; glomerular disease; human anti-CD20 monoclonal antibodies; idiopathic nephrotic syndrome; memory B cells; ofatumumab; prediction of response; rituximab; steroid dependent nephrotic syndrome.

Publication types

  • Comparative Study
  • Equivalence Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Anti-Inflammatory Agents / therapeutic use
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antigens, CD20 / immunology
  • B-Lymphocytes
  • Calcineurin Inhibitors / therapeutic use
  • Child
  • Chimera
  • Drug Therapy, Combination
  • Female
  • Humans
  • Immunoglobulin A / blood
  • Immunoglobulin G / blood
  • Immunologic Factors / adverse effects
  • Immunologic Factors / therapeutic use*
  • Intention to Treat Analysis
  • Maintenance Chemotherapy / methods
  • Male
  • Nephrotic Syndrome / drug therapy*
  • Prednisone / therapeutic use
  • Recurrence
  • Rituximab / adverse effects
  • Rituximab / therapeutic use*
  • Time Factors


  • Anti-Inflammatory Agents
  • Antibodies, Monoclonal, Humanized
  • Antigens, CD20
  • Calcineurin Inhibitors
  • Immunoglobulin A
  • Immunoglobulin G
  • Immunologic Factors
  • Rituximab
  • ofatumumab
  • Prednisone

Associated data

  • EudraCT/2015–000624–28