A Phase I trial of B-cell depletion with anti-CD20 monoclonal antibody (rituximab) in the treatment of systemic lupus erythematosus

We have tested whether the removal of B cells could suppress the manifestations of systemic lupus erythematosus (SLE). Rituximab is a chimeric monoclonal antibody that targets the pan-B-cell marker CD20. Administration of this biologic causes profound depletion of B cells from the peripheral blood for periods of several months. Rituximab has been shown to be efficacious against B-cell malignancies, particularly non-Hodgkins B-cell lymphoma. To begin to determine whether B-cell depletion with rituximab in SLE could be of benefit, we have initiated a phase I safety trial in 12 patients. Patients with SLE with moderate disease activity who had failed at least one cytotoxic drug were eligible for treatment. Nine patients have been entered to date. The first two patients received a low, subtherapeutic dose, but six of the next seven patients received the full approved regimen of 375 mg/m² once a week for four doses. The first two patients developed human antichimeric antibodies, but the next five patients tested did not. The first patient showed an unusual post-infusion reaction, including bradycardia. The other patients tolerated their infusions well. The first five patients who received the full regimen had > 95% depletion of B cells from their peripheral blood 4 weeks after the final dose of rituximab. All patients had lower SLE disease activity index scores after treatment. Three patients with rash and alopecia had improvement. Patient 3 was particularly striking. She had had a recent history of serious renal, pulmonary and infectious complications, treated with cyclophosphamide and high-dose steroids. After rituximab, patient 3 showed the disappearance of activated T cells from the peripheral blood. One year post rituximab treatment she remains off steroids and cytotoxics, and clinically quiescent. The patient's B cells have now returned, with lower levels of CD27 and CD86 than before treatment, and her T cells are still largely unactivated. These uncontrolled data suggest that rituximab is well tolerated in SLE and that it may have some therapeutic benefit. A controlled trial with appropriate outcomes will be necessary to prove whether this approach is indeed efficacious.