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Mycophenolate mofetil for steroid-dependent nephrotic syndrome: a phase II Bayesian trial

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Abstract

Mycophenolate mofetil (MMF) has emerged as a new therapeutic option in steroid-dependent nephrotic syndrome (SDNS). We conducted a phase II Bayesian trial of MMF in children with SDNS. Phase II trials, usually single-arm studies, investigate the effect of new treatments. Standard Fleming’s procedure relies on observed results (relapse rate during the trial), whereas Bayesian approach combines observed results with prior information (expected relapse rate according to prior studies and clinical experience). All patients were required to have received prior alkylating-agent treatment. Sixty-seven percent of them had also received levamisole. Patients received MMF (1,200 mg/m2/day) and prednisone according to a defined schedule [reduction of alternate-day (e.o.d) dose to 50% of pre-MMF dose at 3 months, 25% at 6 months]. Twenty-four children (median age 6.0 years, 2.8–14.4) entered the study and 23 completed it. Bayesian analysis showed that adding four patients would not change significance of results, allowing stopping inclusions. Four patients relapsed during the first 6 months (estimated probability 17.6%, 95% credibility interval: 5.4–35.0%) and two at months 8 and 11.5. In the 19 patients free of relapse during the first 6 months, median (Q1–Q3) prednisone maintenance dose decreased from 25 (10–44) to 9 (7.5–11.2) mg/m2 e.o.d (p < 0.001) and cumulative dose from 459 (382–689) to 264 (196–306) mg/m2/month (p < 0.001) before and on MMF respectively. Pre-MMF patient characteristics and MMF pharmacokinetics did not differ between patients with or without relapse. MMF reduces relapse rate and steroid dose in children with SDNS and should be proposed before cyclosporine and cyclophosphamide.

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Acknowledgements

We thank Wei Zhao for pharmacokinetic studies; Sarah Zohar for support for study design and Bayesian analysis. This work was supported by a research grant from the Département de la Recherche Clinique et du Développement, Assistance Publique–Hôpitaux de Paris, which was also the sponsor of the study (CRC 02 015).

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Authors and Affiliations

  1. Assistance Publique-Hôpitaux de Paris, Hôpital Robert Debré, Pediatric Nephrology Department, Université Paris 7, 48 Boulevard Sérurier, 75019, Paris, France

    Véronique Baudouin, Anne-Laure Lapeyraque, Georges Deschênes & Chantal Loirat

  2. Assistance Publique-Hôpitaux de Paris, Hôpital Robert Debré, Inserm CIE 5, Université Paris 7, Paris, France

    Corinne Alberti

  3. Assistance Publique-Hôpitaux de Paris, Hôpital Trousseau, Pediatric Nephrology Department, Université Paris 6, Paris, France

    Albert Bensman

  4. Hôpital de Brabois, Pediatric Department, Nancy, France

    Jean-Luc André

  5. Hôpital Charles Nicolle, Pediatric Department, Rouen, France

    Françoise Broux

  6. Hôpital de la Timone, Pediatric Nephrology Department, Marseille, France

    Mathilde Cailliez

  7. Hôpital des Enfants, Pediatric Nephrology Department, Toulouse, France

    Stéphane Decramer

  8. Assistance Publique-Hôpitaux de Paris, Hôpital Necker-Enfants Malades, Pediatric Nephrology Department, Université Paris 5, Paris, France

    Patrick Niaudet

  9. Assistance Publique-Hôpitaux de Paris, Hôpital Robert Debré, Pediatric Pharmacology and Pharmacogenetics, Inserm CIC 9202, Université Paris 7, Paris, France

    Evelyne Jacqz-Aigrain

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  1. Véronique Baudouin
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  2. Corinne Alberti
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  3. Anne-Laure Lapeyraque
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  4. Albert Bensman
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  5. Jean-Luc André
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  6. Françoise Broux
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  7. Mathilde Cailliez
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  8. Stéphane Decramer
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  9. Patrick Niaudet
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  10. Georges Deschênes
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  12. Chantal Loirat
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Correspondence to Chantal Loirat.

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Baudouin, V., Alberti, C., Lapeyraque, AL. et al. Mycophenolate mofetil for steroid-dependent nephrotic syndrome: a phase II Bayesian trial. Pediatr Nephrol 27, 389–396 (2012). https://doi.org/10.1007/s00467-011-2006-7

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  • DOI: https://doi.org/10.1007/s00467-011-2006-7

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