Rasburicase Plus Methotrexate Combination Therapy in a Case of Tophaceous, Difficult-to-Treat Gout

拉布立酶联合甲氨蝶呤治疗难治性痛风性痛风

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Abstract

Gout is a disease caused by the deposit of monosodium urate (MSU) crystals that produce joint inflammation and subcutaneous nodules (tophi). The treatment of gout aims to reduce serum uric acid (sUA) levels by administering urate-lowering therapies (ULT) such as xanthine oxidase inhibitors (XOI: allopurinol, febuxostat) or uricosurics (e.g., benzbromarone). However, some patients with tophaceous, difficult-to-treat (D2T) gout may not respond to or have poor tolerance of or contraindications to conventional treatment. Uricases such as pegloticase (PEG; polyethylene glycol-conjugated mammalian recombinant uricase), which degrades UA to allantoin (more soluble in urine), have emerged as a therapeutic alternative for such patients. The concomitant use of methotrexate (MTX) improves the efficacy and tolerance of intravenous PEG by reducing immunogenicity secondary to the formation of anti-PEG antibodies. However, this uricase is not marketed in Europe. Rasburicase, which is indicated for the treatment and prophylaxis of acute hyperuricemia resulting from tumor lysis syndrome in patients undergoing chemotherapy for hematologic malignancies, has been used off-label with some success in tophaceous gout. However, as with PEG, it is occasionally associated with potentially serious infusion reactions. We present a preliminary report on the use of Rasburicase plus MTX combination therapy in treating a single case of refractory tophaceous gout, highlighting potential areas for further investigation.

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