Duke University School of Medicine, Division of Rheumatology and Immunology, Department of Medicine, 4022 Hospital South, Box 2978, Durham, NC, USA.
Orthopedic Physicians Alaska, 3801 Lake Otis Parkway, Anchorage, AK, USA.
Semin Arthritis Rheum. 2021 Apr;51(2):347-352. doi: 10.1016/j.semarthrit.2021.01.005. Epub 2021 Jan 27.
Pegloticase is a recombinant PEGylated uricase that converts relatively insoluble urate to highly water-soluble allantoin, which is readily excreted by the kidneys. It is the first and only biologic treatment indicated for refractory or uncontrolled gout. Clinical trials showed a 6-month pegloticase responder rate of 42%, with the non-responder rate largely being attributed to the development of high-titer anti-drug antibodies (ADAs) against pegloticase. Immunomodulation attenuates ADA formation to biologics in a number of autoimmune conditions, but their use with pegloticase for uncontrolled gout is less established. This systematic review examined published cases of refractory gout patients treated with immunomodulation in combination with pegloticase.
Published cases of immunomodulation with pegloticase were identified in a PubMed search and in abstract databases of major rheumatology society meetings (2012-2020). Duplicate and review articles were excluded, as were those that did not include cases of pegloticase use with immunomodulation. Cases with off-label pegloticase administration schedules were also excluded. Pegloticase response was defined according to each study's specified standard.
Ten publications describing 82 cases of pegloticase use in the setting of immunomodulation were identified. Overall pegloticase response rate was 82.9%. Patients co-treated with an individual immunomodulator had the following response rates: methotrexate: 87.5% (35 of 40 patients), mycophenolate mofetil: 86.4% (19 of 22 patients vs. pegloticase monotherapy [placebo]: 40% [4 of 10 patients]), azathioprine: 63.6% (7 of 11 patients), and leflunomide: 66.7% (4 of 6 patients). A single patient was co-treated with cyclosporin and was a responder. The two patients treated with more than one immunomodulator were both responders.
Published reports suggest that immunomodulation co-therapy has the potential to markedly improve pegloticase responder rates in patients with uncontrolled gout.
聚乙二醇尿酸酶是一种重组聚乙二醇化尿酸酶，可将相对不溶性尿酸转化为高度水溶性的别嘌呤醇，后者可被肾脏轻易排泄。它是第一种也是唯一一种用于治疗难治性或未控制痛风的生物制剂。临床试验显示，6 个月时聚乙二醇尿酸酶的应答率为 42%，未应答者主要归因于针对聚乙二醇尿酸酶产生的高滴度抗药物抗体（ADA）。在许多自身免疫性疾病中，免疫调节剂可减轻生物制剂的 ADA 形成，但在未控制的痛风中使用免疫调节剂治疗聚乙二醇尿酸酶的情况则不太确定。本系统评价研究了已发表的使用免疫调节剂联合聚乙二醇尿酸酶治疗难治性痛风患者的病例。
通过在 PubMed 搜索和主要风湿病学会会议的摘要数据库（2012-2020 年），查找关于免疫调节剂联合聚乙二醇尿酸酶的已发表病例。排除重复和综述文章，以及未包括免疫调节剂联合聚乙二醇尿酸酶使用的病例。也排除了标签外的聚乙二醇尿酸酶给药方案的病例。根据每项研究规定的标准，将聚乙二醇尿酸酶的应答定义为。
确定了 10 篇描述免疫调节剂联合聚乙二醇尿酸酶治疗 82 例病例的出版物。总的聚乙二醇尿酸酶应答率为 82.9%。与单独免疫调节剂联合治疗的患者的应答率如下：甲氨蝶呤：87.5%（40 例患者中的 35 例）、霉酚酸酯：86.4%（22 例患者中的 19 例，而聚乙二醇尿酸酶单药治疗[安慰剂]：40%[10 例患者中的 4 例]）、硫唑嘌呤：63.6%（11 例患者中的 7 例）和来氟米特：66.7%（6 例患者中的 4 例）。一名患者联合环孢素治疗，为应答者。两名联合使用两种免疫调节剂的患者均为应答者。
已发表的报告表明，免疫调节剂联合治疗可能显著提高未控制痛风患者的聚乙二醇尿酸酶应答率。
