Rituximab May Increase Infection Risk in Kidney Transplant Patients

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Use of rituximab in kidney transplant patients is associated with a high risk of infections, according to a French study. In addition, rituximab used in combination with antithymocyte globulin is associated with an increased risk of infection-related death.

Nassim Kamar, MD, of Centre Hospitalier Universitaire Rangueil in Toulouse, and colleagues compared outcomes among 77 kidney-transplant patients who received rituximab therapy (two to eight course of 375 mg/m2 each) and 902 kidney-transplant patients not treated with rituximab (controls).

After a median follow-up of 16.5 months, infectious diseases developed in 35 (45.45%) of the 77 patients treated with rituximab, the researchers reported in the American Journal of Transplantion (2009;9:1-10). The median time between the first rituximab infusion and the first infection was three months. Bacterial, viral, and fungal infections were observed in 36.36%, 18.18%, and 16.88% of patients, respectively. Of the 77 patients, nine (11.68%) died after rituximab therapy. Seven of these deaths (9%) were related to infectious disease (septic shock in three patients, septic shock and mucormycosis in one patient, cryptococcosis in one patient, pneumocystosis in one patient, and acute respiratory distress syndrome in one patient.

In the control group, infectious diseases developed in 486 (53.9%) patients after a median follow-up of 60.9 months was 53.9%. Of the 902 controls, 14 (1.55%) died as a direct result of an infectious disease.

The combined use of rituximab and antithymocyte globulin for induction or anti-rejection therapy was associated with a 5.6 increased risk of infection-related death. The use of rituximab alone and antithymocyte globulin alone was not associated with increased risk.

Dr. Kamar's group concluded that rituximab therapy should be used with caution in kidney-transplant patients. Prophylaxis against cytomegalovirus and Pneumocystis jiroveci should be implemented, and clinicians should closely monitor for infections, mainly in patients who received T-cell depleting agents.

The authors cited a report in Transplant Infectious Disease (2009;11:167-170) describing a case of P. jirovecii pneumonia in a kidney transplant recipient following rituximab therapy for antibody-mediated rejection. They also cited a paper in the European Journal of Haematology (2008;80:275-275) reporting on three case of P. jirovecii pneumonia during first-line treatment with rituximab in patients with non-Hodgkin's lymphoma.

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