Safety of rituximab in children with auto-immune diseases

Purpose

Assessment of safety of rituximab in children with auto-immune diseases (AID) in published reports.

Methods

Pooled analysis of the literature using the Medline database until March 2008.

Results

We identified 169 children treated for refractory AID: autoimmune cytopenia (s) (104 patients), systemic lupus erythematosus (SLE) (52 patients), miscellaneous (13 patients). The mean follow-up period was 6 to 36 months. Patients received 2 to 4 rituximab infusions (350–750 mg/m²) associated with immunosuppressive drugs in 49/52 SLE patients. Replacement intravenous immunoglobulins therapy was given to 68/169 patients. Moderate side effects were observed in 50/169 patients: infusion-related reactions, infections, transient neutropenia > 0.5 × 10⁹/L and serum sickness disease. Severe side effects were observed after rituximab infusion in 11/169 (6.6%) patients: severe infusion related hypotention (4 patients), neutropenia < 0.2 × 10⁹/L (3 patients), (2 SLE patients), cerebral vasculitis (1 SLE patient). Two SLE patients who have received cyclophosphamide died from cerebral histoplasmosis and Staphyloccoccus aureus endocarditis, and one boy who underwent autologous bone marrow transplantation for severe thrombocytopenic purpura developed severe enteroviral meningoencephalitis ; Ig G level was low at time of infection in 3/4 patients and not available in the fifth.

Conclusion

Severe adverse events were recorded in 6.6% of the rituximab-treated children. Patients who have received previous, concurrent and/or subsequent immunosuppressive drugs may experience severe infections, and must be closely monitored. A cohort study of children treated for auto-immune diseases with rituximab has been initiated in France since March 2008 to better assess the tolerance of this therapy.