ESPN 54th Annual Meeting

ESPN 2022


 
Efficacy of Levamisole for Maintaining Remission After the First Flare of Steroid Sensitive Nephrotic Syndrome in Children : the NEPHROVIR-3 randomized controlled trial
CLAIRE DOSSIER 1 THERESA KWON 1 EMELINE CHAPELON 2 CYRIELLE PARMENTIER 3 AURELIEN GALERNE 4 ANNE CHACE 5 MARION CHEMINEE 6 SYLVIE NATHANSON 7 FOUAD MADHI 8 FERIELLE ZENKHRI 1 SEBASTIEN ROUGET 9 OLIVIA BOYER 10 CELIA NEKROUF 11 ALEXANDRA ROUSSEAU 11 JULIEN HOGAN 1

1- PEDIATRIC NEPHROLOGY, ROBERT-DEBRE HOSPITAL, PARIS, APHP
2- DEPARTMENT OF PEDIATRICS, CH VICTOR DUPOUY, ARGENTEUIL
3- PEDIATRIC NEPHROLOGY, ARMAND-TROUSSEAU HOSPITAL, PARIS, APHP
4- DEPARTMENT OF PEDIATRICS, JEAN-VERDIER HOSPITAL, PARIS, APHP
5- DEPARTMENT OF PEDIATRICS, CHI VILLENEUVE SAINT-GEORGES
6- DEPARTMENT OF PEDIATRICS, GH NORD ESSONNE, ORSAY
7- DEPARTMENT OF PEDIATRICS, CH DE VERSAILLES, LE CHESNAY
8- DEPARTMENT OF PEDIATRICS, CHI CRéTEIL
9- DEPARTMENT OF PEDIATRICS, CHSF, CORBEIL-ESSONNES
10- PEDIATRIC NEPHROLOGY, NECKER HOSPITAL, PARIS, APHP
11- URC-EST, SAINT-ANTOINE HOSPITAL, PARIS, APHP
 
Introduction:

 In children with Steroid Sensitive Nephrotic Syndrome (SSNS), relapse after the first flare occurs in 80% of cases, whatever the dosage or duration of initial steroid therapy. Therefore, there is an unmet need for early interventions to reduce incidence of early relapses. Levamisole is an antihelmintic drug with an immunomodulatory action that reduces relapses in children with Frequent Relapses or Steroid Dependant NS. NEPHROVIR-3 is the first trial to assess the efficacy of levamisole in increasing duration of initial remission after the diagnosis of INS.


Material and methods:

 NEPHROVIR-3 is a multicentric placebo-controlled randomized   trial (1:1), in 38 centers of the Paris area, France. Patients were included at INS diagnosis and randomized, when steroid sensitive within 4 weeks, to receive either levamisole 2.5 mg/kg/48h or placebo for 6 months, in addition to the French steroid protocol (18 weeks-3990mg/m2). Primary outcome was the relapse-free survival at 1 year. The effect of the study drug was analysed by a  Cox proportional hazard model stratified on centre.

Results:

 Between September 2017 and February 2020, 86 patients were included, median age at INS onset was 5 yrs (IQ 3-7), with 69% of boys.  At 4 weeks, 68 of them were randomized. Median time to remission was 8.5 days (IQ 6-12). Relapse-free survival at 12 months was 53.8% (95%IC 34.7-69.5) in the levamisole group versus 20.9% (7.2-39.4) in the placebo group (p=0.007). The risk of relapse associated with levamisole was HR =0.37 (95%IC 0.15-0.89). Treatment was well tolerated with one interruption in each group because of skin rash. 

Conclusions:

 Early treatment with levamisole at the first flare of childhood SSNS is well tolerated and significantly improves relapse-free survival at 1 year.