Pietro Ravani1, Manuela Colucci2, Maurizio Bruschi3, Marina Vivarelli4, Michela Cioni3, Armando DiDonato3, Paolo Cravedi5, Francesca Lugani3, Francesca Antonini6, Marco Prunotto7, Francesco Emma4, Andrea Angeletti8, Gian Marco Ghiggeri9,8. 1. Division of Nephrology, University of Calgary, Calgary, Alberta, Canada. 2. Renal Diseases Research Unit, Genetics and Rare Diseases Division, Bambino Gesù Children's Hospital Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy. 3. Laboratory on Molecular Nephrology, Division of Nephrology, Dialysis, Transplantation, Istituto Giannina Gaslini Istituto di Ricovero e Cura a Carattere Scientifico, Genoa, Italy. 4. Division of Nephrology, Bambino Gesù Children's Hospital Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy. 5. Renal Division, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York. 6. Core Facilities, Istituto di Ricovero e Cura a Carattere Scientifico Istituto G. Gaslini, Genoa, Italy. 7. Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, Switzerland. 8. Division of Nephrology, Dialysis, Transplantation, Istituto Giannina Gaslini Istituto di Ricovero e Cura a Carattere Scientifico, Genoa, Italy. 9. Laboratory on Molecular Nephrology, Division of Nephrology, Dialysis, Transplantation, Istituto Giannina Gaslini Istituto di Ricovero e Cura a Carattere Scientifico, Genoa, Italy gmarcoghiggeri@gaslini.org.
Abstract
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 After infusions, oral drugs were tapered and withdrawn within 60 days.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).
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).
Authors: Fernando C Fervenza; Roshini S Abraham; Stephen B Erickson; Maria Valentina Irazabal; Alfonso Eirin; Ulrich Specks; Patrick H Nachman; Eric J Bergstralh; Nelson Leung; Fernando G Cosio; Marie C Hogan; John J Dillon; LaTonya J Hickson; Xujian Li; Daniel C Cattran Journal: Clin J Am Soc Nephrol Date: 2010-08-12 Impact factor: 8.237
Authors: Chris Wincup; Madhvi Menon; Edward Smith; Ann Schwartz; David Isenberg; Elizabeth C Jury; Claudia Mauri Journal: Ann Rheum Dis Date: 2019-03-28 Impact factor: 19.103