Pegloticase可为严重慢性难治性痛风的“桥”治疗

摘要 在美国，难治性痛风患者约有5万个，约占患者总数的1%，其严重性主要表现为致残性关节炎反复急性发作、慢性畸形性关节病变、破坏性痛风石形成、进行性残疾和健康相关的生活质量降低。Pegloticase是由Savient药厂生产，是一种新的PEG化尿酸氧化酶（尿酸酶）再次提请美国FDA批准上市(注:目前已批准上市)。在6个月的安慰剂对照临床试验中发现，Pegloticase 8mg,每2周1次可使血尿酸降低，最终40%的痛风石溶解，然而有58%患者的血尿酸不能降低到0.36mmol/L以下(第3个月和第6个月为80%)，也许是因产生抗体所致。而且，有26%-31%的患者出现输液反应，77%有痛风发作。虽然其最终结论尚有待于长期研究，但初期使用时同时的抗炎（如用激素）有助于防止其抗体形成导致输液反应和降低或缩短疗效，并也许可防止痛风发作。根据目前的临床资料，Pegloticase可能是一种对严重慢性难治性痛风清除痛风石的很重要的“桥”治疗。

附原文 Abstract Treatment-failure gout (TFG) affects approximately 50,000 patients or about 1% of the overall population of patients with gout in the United States of America. The severity of TFG is manifested by frequent acute attacks of disabling arthritis, chronic deforming joint disease, destructive masses of urate crystals (tophi), progressive physical disability, and poor health-related quality of life. Pegloticase (Krystexxa(®); Savient Pharmaceuticals, Inc), a novel PEGylated urate oxidase (uricase) enzyme, has been resubmitted for US Food and Drug Administration approval. In a 6-month, placebo-controlled clinical trial, 8 mg of pegloticase for every 2 weeks induced a lytic decrease of serum urate (sUr) concentrations, leading to dissolution of tophi in 40% of patients at final visit. However, 58% were nonresponders to the defined target sUr of 0.36 mmol/L (80% were nonresponders during months 3 and 6), possibly due to anti-body formation. Also, 26%-31% experienced infusion reactions (IRs) and 77% suffered from gout flares. Although long-term data are awaited, an anti-inflammatory strategy, eg, based on glucocorticosteroids, is needed to prevent pegloticase antibody formation leading to IRs and diminished or shortened efficacy, and might also prevent gout flares. According to the current clinical data, pegloticase might have an important role as a (bridging) treatment in sUr-responsive patients for tophi clearance in severe chronic refractory gout.

引自：Reinders MK, Jansen TL. New advances in the treatment of gout: review of pegloticase. Source. Ther Clin Risk Manag,2010,27(6):543-50.