Recapture and improved outcome of pegloticase response with methotrexate-A report of two cases and review of the literature.

INTRODUCTION: Pegloticase is a PEGylated uric acid specific enzyme indicated for the treatment of refractory gout. Anti-pegloticase antibodies contribute to high discontinuation rates, increased risk of infusion reactions, and early loss of drug efficacy. OBJECTIVE: To describe the use of methotrexate to recapture function of pegloticase after development of anti-drug antibodies while treating gout. METHODS: We report two cases of using methotrexate as an adjunct to treatment with pegloticase for refractory tophaceous gout. We also present the results of a literature review on the use of concomitant immunosuppressive therapy with pegloticase to prevent anti-pegloticase antibody development. RESULTS: Patient A, a 55-year-old man with a history of tophaceous gout, was treated with pegloticase but developed high serum urate(sUA) levels prior to his third infusion. Adjunctive treatment with methotrexate restored pegloticase response and the patient's sUA levels decreased, and remained low for the remainder of his treatment. Patient B, a 36-year-old man with a history of tophaceous gout, was treated with pegloticase. Oral methotrexate was initiated at the first infusion. Low sUA levels were achieved but increased after a lapse in methotrexate compliance. Re-initiation of methotrexate restored pegloticase response and the patient tolerated subsequent infusions. Literature review identified three reports of successful use of concomitant pegloticase and immunosuppressive therapy for refractory tophaceous gout, including an open label trial with a subset of 7 transplant recipients, an additional case study of pegloticase treatment with one transplant recipient, and a case study of pegloticase administered with low-dose azathioprine. CONCLUSION: Prophylactic use of immunosuppressive therapy with pegloticase may enable sustained treatment and improve outcomes. Additionally, immunosuppressive therapy seems to show the ability to recapture pegloticase response after development of anti-drug antibodies. The use of immunosuppressants to prevent anti-drug antibody formation, recapture pegloticase efficacy, and reduce discontinuation rates warrants further study.

Increased risk of coccidioidomycosis in patients treated with tumor necrosis factor alpha antagonists.

OBJECTIVE: To describe a group of patients who were treated with tumor necrosis factor alpha (TNF alpha) antagonists and who developed coccidioidomycosis, and to test the hypothesis that patients with inflammatory arthritis receiving TNF alpha antagonist therapy are at higher risk for developing symptomatic coccidioidomycosis. METHODS: Cases of coccidioidomycosis were identified and reviewed from among patients receiving TNF alpha antagonist therapy from May 1998 through February 2003 in 5 practices within the areas endemic for coccidioidomycosis (Arizona, California, and Nevada). In addition, the relative risk of developing symptomatic coccidioidomycosis was calculated in patients with inflammatory arthritis who were receiving treatment with infliximab, in comparison with patients with inflammatory arthritis who were not receiving infliximab, from January 2000 to February 2003 in a single medical center. RESULTS: Thirteen cases of documented coccidioidomycosis were associated with TNF alpha antagonist therapy. Twelve cases were associated with the use of infliximab and 1 case with etanercept. Among the cohort of patients from a single medical center, 7 of the 247 patients receiving infliximab and 4 of the 738 patients receiving other therapies developed symptomatic coccidioidomycosis (relative risk 5.23, 95% confidence interval 1.54-17.71; P < 0.01). CONCLUSION: Patients with inflammatory arthritis who are undergoing treatment with infliximab appear to be at higher risk for developing symptomatic coccidioidomycosis as compared with those not receiving infliximab.