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Abstract: SA-OR74

Initial Treatment of Idiopathic Nephrotic Syndrome in Children with Mycophenolate Mofetil vs. Prednisone: A Prospective, Randomized, Controlled, Multicenter, Open, Phase 3, Noninferiority Study

Session Information

Category: Pediatric Nephrology

  • 1900 Pediatric Nephrology

Authors

  • Benz, Marcus R., University Hospital of Cologne, Cologne, Germany
  • Ehren, Rasmus, University Hospital of Cologne, Cologne, Germany
  • Höcker, Britta, University Children`s Hospital Heidelberg, Heidelberg, Germany
  • Fichtner, Alexander, University Children`s Hospital Heidelberg, Heidelberg, Germany
  • Querfeld, Uwe, Charite Universitatsmedizin Berlin, Berlin, Berlin, Germany
  • Hoyer, Peter F., Universitat Duisburg-Essen, Duisburg, Nordrhein-Westfalen, Germany
  • Kemper, Markus J., Asklepios Kliniken GmbH & Co KGaA, Hamburg, Hamburg, Germany
  • Haffner, Dieter, Medizinische Hochschule Hannover Zentrum fur Kinderheilkunde und Jugendmedizin, Hannover, Niedersachsen, Germany
  • Dotsch, Jörg, University Hospital of Cologne, Cologne, Germany
  • Konrad, Martin, Universitat Munster, Munster, Nordrhein-Westfalen, Germany
  • Sander, Anja Christine, Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany
  • Meis, Jan, Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany
  • Toenshoff, Burkhard, University Children`s Hospital Heidelberg, Heidelberg, Germany
  • Weber, Lutz Thorsten, University Hospital of Cologne, Cologne, Germany

Group or Team Name

  • German Society of Pediatric Nephrology (GPN).
Background

Initial treatment of idiopathic nephrotic syndrome (iNS) in children requires sufficient immunosuppressive therapy to induce and sustain remission and consists of a prolonged course with glucocorticoids (GC). Even though being effective, this treatment is associated with pronounced GC associated toxicity.
Mycophenolate mofetil (MMF) is effective in sustaining remission in patients with frequently relapsing or GC-dependent nephrotic syndrome.
The hypothesis of the INTENT-Study (initial treatment of idiopathic nephrotic syndrome in children with mycophenolate mofetil vs. prednisone) was that MMF is not inferior to standard therapy with GC in the iNS in children with regard to maintenance of remission and subsequent recurrence rate.

Methods

272 children (mean age at onset 4.1±2.3 years; 64.3% males) with a first episode of SSNS were randomized to either standard treatment (12 weeks of GC) or experimental treatment (MMF only after induction of remission with GC for a total treatment period of 12 weeks). Primary end-point was occurrence of treated relapse within follow-up of 24 months after completion of initial treatment. Secondary end-points included i.a. course of the disease and drug toxicities.

Results

MMF was not inferior to GC treatment in terms of the primary end-point (imputed mITT set: relapse rate 79.1% (MMF group) vs. 74.8% (GC group), difference 4.3% [-4.2%;12.7%], p=0.019; imputed per protocol set: relapse rate 79.2% (MMF group) vs. 77.7% (GC group), difference 1.5% [-7.7%;10.8%], p=0.008). In the MMF arm, there were fewer GC-related side effects, such as lower blood pressure and body mass index as well as less frequent psychological abnormalities and cushingoid appearance. Cytopenias were more frequent in the MMF group but overall rare and mild. The rate of frequently relapsing nephrotic syndrome in the follow-up was comparable between the groups (MMF: 47.2%, GC: 45.2%).

Conclusion

The presented results of the INTENT-Study show non-inferiority of the MMF arm to the standard GC arm with no safety concerns and fewer GC-related side effects. They have the potential to alter the standard of care in SSNS.

Funding

  • Government Support – Non-U.S.