Human or Chimeric Monoclonal Anti-CD20 Antibodies for Children with Nephrotic Syndrome: A Superiority Randomized Trial.
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 After infusions, oral drugs were tapered and withdrawn within 60 days.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
ClinicalTrials.gov (NCT02394119) and https://www.clinicaltrialsregister.eu/ctr-search/search (2015-000624-28).
['Ravani|Pietro|P|', 'Colucci|Manuela|M|', 'Bruschi|Maurizio|M|', 'Vivarelli|Marina|M|', 'Cioni|Michela|M|', 'DiDonato|Armando|A|', 'Cravedi|Paolo|P|', 'Lugani|Francesca|F|', 'Antonini|Francesca|F|', 'Prunotto|Marco|M|', 'Emma|Francesco|F|0000-0002-0383-3468', 'Angeletti|Andrea|A|', 'Ghiggeri|Gian Marco|GM|']
rituximab ofatumumab human anti-CD20 monoclonal antibodies calcineurin inhibitor-dependent nephrotic syndrome antirituximab antibodies glomerular disease idiopathic nephrotic syndrome memory B cells prediction of response steroid dependent nephrotic syndrome