A randomized, doubleblind, placebo-controlled, study of single-dose rituximab as induction in renal transplantation.
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.


CONCLUSIONS
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.
Tydén
Gunnar
G
Department of Transplantation Surgery, Karolinska University Hospital, Stockholm, Sweden. gunnar.tyden@karolinska.se
Genberg
Helena
H
Tollemar
Jan
J
Ekberg
Henrik
H
Persson
Nils H
NH
Tufveson
Gunnar
G
Wadström
Jonas
J
Gäbel
Markus
M
Mjörnstedt
Lars
L
D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D015703:Antigens, CD / Q000032:analysis; D018941:Antigens, CD19 / Q000032:analysis; D018951:Antigens, CD20 / Q000032:analysis; D002102:Cadaver; D004311:Double-Blind Method; D005260:Female; D006084:Graft Rejection / Q000453:epidemiology; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000276:immunology* / Q000401:mortality; D019520:Living Donors; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D010919:Placebos; D012086:Reoperation / Q000706:statistics & numerical data; D000069283:Rituximab; D012449:Safety; D016019:Survival Analysis; D014019:Tissue Donors; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D015703:Antigens, CD; D018941:Antigens, CD19; D018951:Antigens, CD20; D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D010919:Placebos; D000069283:Rituximab; D009173:Mycophenolic Acid