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Efficacy and safety of intravenous immunoglobulin with rituximab versus rituximab alone in childhood-onset steroid-dependent and frequently relapsing nephrotic syndrome: protocol for a multicentre randomised controlled trial.

ABSTRACT: INTRODUCTION:Guidelines for the treatment of steroid-dependent nephrotic syndrome (SDNS) and frequently relapsing nephrotic syndrome (FRNS) are lacking. Given the substantial impact of SDNS/FRNS on quality of life, strategies aiming to provide long-term remission while minimising treatment side effects are needed. Several studies confirm that rituximab is effective in preventing early relapses in SDNS/FRNS; however, the long-term relapse rate remains high (~70% at 2 years). This trial will assess the association of intravenous immunoglobulins (IVIgs) to rituximab in patients with SDNS/FRNS and inform clinicians on whether IVIg's immunomodulatory properties can alter the course of the disease and reduce the use of immunosuppressive drugs and their side effects. METHODS AND ANALYSIS:We conduct an open-label multicentre, randomised, parallel group in a 1:1 ratio, controlled, superiority trial to assess the safety and efficacy of a single infusion of rituximab followed by IVIg compared with rituximab alone in childhood-onset FRNS/SDNS. The primary outcome is the occurrence of first relapse within 24 months. Patients are allocated to receive either rituximab alone (375 mg/m²) or rituximab followed by IVIg, which includes an initial Ig dose of 2?g/kg, followed by 1.5?g/kg injections once a month for the following 5?months (maximum dose: 100?g). ETHICS AND DISSEMINATION:The study has been approved by the ethics committee (Comité de Protection des Personnes) of Ouest I and authorised by the French drug regulatory agency (Agence Nationale de Sécurité du Médicament et des Produits de Santé). Results of the primary study and the secondary aims will be disseminated through peer-reviewed publications. TRIAL REGISTRATION NUMBER:NCT03560011.

SUBMITTER: Hogan J

PROVIDER: S-EPMC7513594 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Efficacy and safety of intravenous immunoglobulin with rituximab versus rituximab alone in childhood-onset steroid-dependent and frequently relapsing nephrotic syndrome: protocol for a multicentre randomised controlled trial.

Hogan Julien J Perez Aubriana A Sellier-Leclerc Anne-Laure AL Vrillon Isabelle I Broux Francoise F Nobili Francois F Harambat Jerome J Bessenay Lucie L Audard V V Faudeux Camille C Morin Denis D Pietrement Christine C Tellier Stephanie S Djeddi Djamal D Eckart Philippe P Lahoche Annie A Roussey-Kesler G G Ulinski Tim T Boyer Olivia O Plaisier Emmanuelle E Cloarec Sylvie S Jolivot Anne A Guigonis Vincent V Guilmin-Crepon Sophie S Baudouin Veronique V Dossier Claire C Deschênes Georges G

BMJ open 20200923 9

<h4>Introduction</h4>Guidelines for the treatment of steroid-dependent nephrotic syndrome (SDNS) and frequently relapsing nephrotic syndrome (FRNS) are lacking. Given the substantial impact of SDNS/FRNS on quality of life, strategies aiming to provide long-term remission while minimising treatment side effects are needed. Several studies confirm that rituximab is effective in preventing early relapses in SDNS/FRNS; however, the long-term relapse rate remains high (~70% at 2 years). This trial wi ...[more]

PMID: 32967877

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Project description:Background: We aimed to investigate the effects of intravenous immune globulin (IVIG) and rituximab desensitization treatment on kidney transplant rate and blood gene expression profiles by microrarrays. Methods: We enrolled patients with PRA levels >50% and on the deceased-donor waiting list for >5 years. Patients received IVIG (2.0 g/kg) on day 0 and 30; and rituximab (375 mg/m2) on day 15. The antibodies with mean fluorescence intensity (MFI) values > 5,000 were reported to UNET as unacceptable antigens. The gene expression profiles of blood samples collected in PAXGene tube were studied by Affymetrix HuGene 1.0 ST expression arrays. Results: 40 of the 415 patients (10%) on the waiting list were eligible for desensitization treatment and 11 completed the treatment. While 15 of the remaining 29 patients (52%) received a transplant without therapy, only 2 of the 11 desensitized patients (18%) received transplant during a median follow-up of 217 days. While there were no statistically significant difference in demographics, desensitized patients had higher cPRA values (97% vs. 77%, p=0.0005) and more number of unacceptable antigens (39 vs. 10, p=0.0001). There was no significant change in the mean number of unacceptable antigens (39 ± 22 versus 39 ± 23) or reduction in the mean MFI values (11,333 ± 3,133 vs 11,289 ± 3,386). Analysis of genes chosen as significantly differentially expressed revealed downregulation of genes involved in B cells and immune system (CD79a, B and T lymphocyte associated transcript, B cell scaffold protein, CD22, CXCR5, fas apoptotic inhibitory protein). Gene set enrichment analysis using Pathogenesis Based Transcripts created by Edmonton Group demonstrated significant downregulation of B cell associated (p=0.04) and immunoglobulin transcripts (p=0.03). Conclusion: Although, desensitization with IVIG and rituximab decreases the expression of B cell and immunoglobulin associated transcripts, it was not successful in increasing kidney transplant rate or in decreasing the number of unacceptable antigens.

Dataset Information

Efficacy and safety of intravenous immunoglobulin with rituximab versus rituximab alone in childhood-onset steroid-dependent and frequently relapsing nephrotic syndrome: protocol for a multicentre randomised controlled trial.

Publications

Efficacy and safety of intravenous immunoglobulin with rituximab versus rituximab alone in childhood-onset steroid-dependent and frequently relapsing nephrotic syndrome: protocol for a multicentre randomised controlled trial.

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