Use of Rituximab to Attempt Recapture of Immune Tolerance to Pegloticase

Patients suffering from erosive tophaceous gout who have failed oral urate-lowering therapies and pegloticase have few therapeutic options. Pegloticase failure (infusion reaction or lack of urate lowering) is primarily due to the development of anti-drug antibodies, and once present, retreating with pegloticase is mostly unsuccessful. We postulated that rituximab pre-treatment might permit recapture of pegloticase immune tolerance. We conducted an open label, safety and feasibility study to test this hypothesis. Patients with tophaceous gout and prior pegloticase failure were recruited to receive rituximab 1000 mg (twice), methotrexate 15 mg by mouth for at least 6 weeks, and then pegloticase per standard protocol. Patients were observed for infusion reaction and serum urate lowering in response to pegloticase infusions. Two patients completed induction and received at least 1 dose of pegloticase. Patient 1 had a moderate infusion reaction, requiring treatment with oral prednisone. Patient 2 had failure to lower urate treatment after 2 infusions. Based on these 2 outcomes, the trial was stopped. With either 6- or 12-week pre-pegloticase conditioning with rituximab, we were unable to recapture immune tolerance. Future trials considering use of rituximab might consider measuring anti-uricase antibodies in real time to guide the reintroduction of pegloticase.