Rituximab for Prevention of Rejection After Renal Transplantation

Summary

Our standard immunosuppressive treatment after renal transplantation is a combination of tacrolimus, mycophenolate mofetil, and prednisolone. With this regimen the incidence of acute rejection within the first six months after transplantation has dropped to about 20%. The main challenge at present remains to improve long-term outcome by preventing chronic allograft nephropathy (CAN). Since acute rejection is a strong predictor of CAN, a further decrease in the incidence of acute rejection can improve the long-term graft survival. Current strategies to prevent rejection are mainly directed at alloreactive T cells. Recently, the attention for the role of antibodies in the pathogenesis of acute rejection has increased. In addition, anti-B cell therapy was shown to be effective in diseases that were considered to be mainly T cell driven, like rheumatoid arthritis. In the latter case it has been suggested that anti-B cell antibodies may impair the antigen presenting function of B cells. We therefore decided to investigate the effectiveness and safety of the anti-B cell monoclonal antibody rituximab for prophylaxis of acute rejection after renal transplantation. Study design: Double-blind, placebo controlled intervention study. One group receives a single dose of rituximab of 375 mg/m2 intravenously at the time of transplantation, and the other group receives a placebo infusion. Primary Objective: To determine the incidence and severity of biopsy-confirmed acute rejection within the first six months after transplantation. Secondary Outcomes: * Renal function as estimated by the endogenous creatinine clearance at 6 months * Occurrence of chronic allograft nephropathy at 6 months * Cumulative incidence of infections and malignancies at 6 months * Medical costs during the first 6 months after transplantation * Patient and graft survival

Timeline

Start

2007-12

Primary completion

2013-12

Completion

2015-06

Publications

• Background Pescovitz MD. Rituximab, an anti-cd20 monoclonal antibody: history and mechanism of action. Am J Transplant. 2006 May;6(5 Pt 1):859-66. doi: 10.1111/j.1600-6143.2006.01288.x.
• Kamburova EG, Koenen HJ, van den Hoogen MW, Baas MC, Joosten I, Hilbrands LB. Longitudinal analysis of T and B cell phenotype and function in renal transplant recipients with or without rituximab induction therapy. PLoS One. 2014 Nov 13;9(11):e112658. doi: 10.1371/journal.pone.0112658. eCollection 2014.
• Smeekens SP, van den Hoogen MW, Kamburova EG, van de Veerdonk FL, Joosten I, Koenen HJ, Netea MG, Hilbrands LB, Joosten LA. The effects of in vivo B-cell depleting therapy on ex-vivo cytokine production. Transpl Immunol. 2013 Jun;28(4):183-8. doi: 10.1016/j.trim.2013.04.008. Epub 2013 May 4.

Drugs

Indications

No indication recorded.