A Randomized, Doubleblind, Placebo-Controlled, Study of Single-Dose Rituximab as Induction in Renal Transplantation
Tydén G, Genberg H, Tollemar J, Ekberg H, Persson NH, Tufveson G, Wadström J, Gäbel M, Mjörnstedt L. Transplantation. 2009 May 15;87(9):1325-9
This is the first RCT assessing the effect of rituximab compared to no induction therapy in patients receiving tacrolimus, mycophenolate mofetil and steroids. Rituximab durably depleted B cells. There was no increase in the incidence of infections with rituximab but also did not reduce the incidence of acute rejection or lead to improved graft function.
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Abstract:
We performed a prospective, double blind, randomized, placebo-controlled multicenter study on the efficacy and safety of rituximab as induction therapy, together with tacrolimus, mycophenolate mofetil, and steroids. The primary endpoint was defined as acute rejection, graft loss, or death during the first 6 months. Secondary endpoints were creatinine clearance, incidence of infections, and incidence of rituximab-related adverse event. RESULTS: We enrolled 140 patients (44 living donor and 96 deceased donor), and of those, 68 rituximab and 68 placebo patients fulfilled the study. In all the patients receiving rituximab, there was a complete depletion of CD19/CD20 cells, whereas there was no change in the number of CD19/CD20 cells in the placebo group. There were 10 treatment failures in the rituximab group versus 14 in the placebo group (P=0.348). There were eight rejection episodes in the rituximab group versus 12 in the placebo group (P=0.317) Creatinine clearance was 66+/-22 mL/min in the study group and 67+/-23 mL/min in the placebo group. There was no difference in the number of bacterial infections, cytomegalovirus infections, and BK virus infections or fungal infections. CONCLUSION: We performed a placebo-controlled study of rituximab induction in renal transplantation. There was a tendency toward fewer and milder rejections during the first 6 months in the rituximab group. Although induction with one dose of rituximab induced a complete depletion B cells, there was no increase in the incidence of infectious complications or leukopenia and it seems safe, therefore, to conduct further studies on the use of rituximab in transplantation.
July 21st, 2009 at 11:07 am
The study is well done though does not introduce any new induction treatment. The primary end point did not show any increase in rejection or in other words did not show non inferiority of Riruximab to other existing agents. There was no evidence for increase in incidence of infection after induction. The transplantation area has been lacking new medicine which can address the induction of tolerance. Most immunosuppressive only target early phases of T cells activation, preventing them from producing cytokines required for their proliferation. It remains to be seen where monoclonal antibodies used for induction can promote tolerance rather destroying the regulatory mechanism important for the tolerance.