Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, U.S.A.
AMPEL BioSolutions, LLC, Charlottesville, Virginia, U.S.A.
Semin Arthritis Rheum. 2020 Jun;50(3S):S31-S38. doi: 10.1016/j.semarthrit.2020.04.011.
Gout is currently the most frequent cause of inflammatory arthritis worldwide. It results from elevated serum urate and subsequent deposition of monosodium urate crystals in joints and other tissues. While many patients with gout can be managed with conventional agents (e.g., allopurinol, febuxostat), those with chronic refractory gout often fail to achieve treatment goals with these agents. Pegloticase is a recombinant, pegylated mammalian uricase developed for treatment of chronic refractory gout. Pegloticase is different than other urate lowering therapies in that it enzymatically degrades urate. Pegloticase has been evaluated in multiple studies, most importantly in two randomized controlled trials and a follow-up open-label extension. Extensive analysis of results from these studies has shown that pegloticase profoundly lowers serum urate, resolves tophi, reduces tender and swollen joint counts, decreases pain, and improves both patients' global assessments and quality of life. Pegloticase also significantly decreases blood pressure in patients with chronic refractory gout, but has no significant effect on renal function. Post hoc analyses of clinical results also indicated that chronic refractory gout patients not achieving sustained urate lowering still have significant clinical benefits with pegloticase treatment. The major limitation of pegloticase is immunogenicity and the emergence of anti-drug antibodies that result in increased drug clearance, loss of efficacy, and infusion reactions. However, these reactions can be avoided by stopping pegloticase when there is a loss of serum urate lowering. New dosing regimens and co-administration of immunosuppressive agents are also being employed to overcome this limitation and extend the benefits of pegloticase to a larger number of patients.
痛风是目前全球最常见的炎症性关节炎病因。它是由于血清尿酸升高，随后单钠尿酸盐晶体在关节和其他组织中沉积所致。虽然许多痛风患者可以通过常规药物（如别嘌醇、非布司他）进行治疗，但那些慢性难治性痛风患者往往无法通过这些药物达到治疗目标。培戈洛酶是一种重组的、聚乙二醇化的哺乳动物尿酸酶，用于治疗慢性难治性痛风。培戈洛酶与其他降低尿酸的疗法不同，它可以酶解尿酸。培戈洛酶已在多项研究中进行了评估，最重要的是两项随机对照试验和一项后续开放标签扩展研究。对这些研究结果的广泛分析表明，培戈洛酶能显著降低血清尿酸、溶解痛风石、减少关节压痛和肿胀数、减轻疼痛，并改善患者的整体评估和生活质量。培戈洛酶还可显著降低慢性难治性痛风患者的血压，但对肾功能无显著影响。对临床结果的事后分析还表明，未能持续降低尿酸的慢性难治性痛风患者仍能从培戈洛酶治疗中获得显著的临床获益。培戈洛酶的主要局限性是免疫原性和产生抗药物抗体，导致药物清除率增加、疗效丧失和输注反应。然而，当血清尿酸降低丢失时，停止培戈洛酶治疗可以避免这些反应。新的给药方案和免疫抑制药物的联合使用也被用来克服这一限制，使更多的患者受益于培戈洛酶。
