Rituximab as Induction Therapy After Renal Transplantation: A Randomized, Double-Blind, Placebo-Controlled Study of Efficacy and Safety

Abstract

We evaluated the efficacy and safety of rituximab as induction therapy in renal transplant patients. In a double‐blind, placebo‐controlled study, 280 adult renal transplant patients were randomized between a single dose of rituximab (375 mg/m2) or placebo during transplant surgery. Patients were stratified according to panel‐reactive antibody (PRA) value and rank number of transplantation. Maintenance immunosuppression consisted of tacrolimus, mycophenolate mofetil and steroids. The primary endpoint was the incidence of biopsy proven acute rejection (BPAR) within 6 months after transplantation. The incidence of BPAR was comparable between rituximab‐treated (23/138, 16.7%) and placebo‐treated patients (30/142, 21.2%, p = 0.25). Immunologically high‐risk patients (PRA >6% or re‐transplant) not receiving rituximab had a significantly higher incidence of rejection (13/34, 38.2%) compared to other treatment groups (rituximab‐treated immunologically high‐risk patients, and rituximab‐ or placebo‐treated immunologically low‐risk (PRA ≤ 6% or first transplant) patients (17.9%, 16.4% and 15.7%, p = 0.004). Neutropenia (<1.5 × 109/L) occurred more frequently in rituximab‐treated patients (24.3% vs. 2.2%, p < 0.001). After 24 months, the cumulative incidence of infections and malignancies was comparable. A single dose of rituximab as induction therapy did not reduce the overall incidence of BPAR, but might be beneficial in immunologically high‐risk patients. Treatment with rituximab was safe.

ABO-Incompatible Living Kidney Transplant Recipients from Spousal Donors Receiving Rituximab

“…Previous reports suggested that B cell-related cytokines might play a role in late-onset neutropenia [18,19]. It was also reported that treatment with rituximab in kidney transplantation was associated with a significantly higher cumulative incidence of neutropenia [20]. However, the higher incidence of neutropenia in recipients receiving rituximab did not lead to more infections, which is in accordance with the results of other studies [21].…”

Repeat Kidney Transplantation

“…В группу повышенного иммунологического риска вошли пациенты с уровнем предсуществу-ющих антител более 6% и/или перенесшие транс-плантацию почки в анамнезе. Результаты показали достоверно большую частоту отторжений в груп-пе пациентов высокого иммунологического риска, получавших плацебо (38%), по сравнению с тремя остальными группами, где частота отторжений со-ставила 16-18% [84].…”

Untitled

“…41 van den Hoogen and associates conducted a randomized controlled trial to assess the efficacy of rituximab as an induction agent in both low-and highrisk kidney transplant recipients. 42 In this study, a PRA of > 6% or retransplant were considered as factors indicating high immunologic risk. Patients were randomized to either a single dose of 375 mg/m 2 of rituximab (n = 138) or placebo (n = 142).…”