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Comment & Response
May 24, 2021

Inadequate Dosage of Mycophenolate Mofetil Is Likely to Yield Substandard Trial Results and Substandard Patient Care

Author Affiliations
  • 1Department of Pediatric Nephrology, RadboudUMC, Radboud Institute for Molecular Life Sciences, Amalia Children’s Hospital, Nijmegen, the Netherlands
  • 2Pediatric Nephrology, Children’s and Adolescents’ Hospital, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany
JAMA Pediatr. 2021;175(8):869-870. doi:10.1001/jamapediatrics.2021.1071

To the Editor The rituximab study by Ravani et al1 was designed to show the superiority of a rituximab biosimilar over mycophenolate mofetil (MMF) to maintain remission in children and young adults with steroid-dependent nephrotic syndrome (SDNS). As stated by the authors, MMF is well established as a steroid-sparing agent in SDNS. In contrast to the statement of the authors, previous studies have shown that individual exposure determined by therapeutic drug monitoring is highly relevant in the efficacy of preventing relapses.2-4 Children taking 1000 to 1200 mg/m2 daily were best protected against relapses when reaching an area under the receiver operating characteristic curve (AUC) greater than 45 to 50 μg × h/mL.2-4 Therefore, it comes as no surprise that the low dose of MMF of 700 mg/m2 per day used in the study by Ravani et al1 was unsuccessful in maintaining remission. Using such a substandard dosage makes it likely that a difference can be detected with the rituximab biosimilar intervention, which was defined as the objective in the study protocol.1 But it is doubtful that such a finding is helpful for clinical practice, and the authors state that a higher dose deserves testing in future studies. The rationale behind choosing a substandard dose of MMF remains unclear. Of note, the uncontrolled study by Novak et al cited in this study1 found a positive effect with standard-dose MMF (1200 mg/m2 per day).

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