Arthritis Res Ther. 2013 Sep 26;15(5):R137. doi: 10.1186/ar4318.
Two replicate randomized, placebo-controlled six-month trials (RCTs) and an open-label treatment extension (OLE) comprised the pegloticase development program in patients with gout refractory to conventional therapy. In the RCTs, approximately 40% of patients treated with the approved dose saw complete response (CR) of at least one tophus. Here we describe the temporal course of tophus resolution, total tophus burden in patients with multiple tophi, tophus size at baseline, and the relationship between tophus response and urate-lowering efficacy.
Baseline subcutaneous tophi were analyzed quantitatively using computer-assisted digital images in patients receiving pegloticase (8 mg biweekly or monthly) or placebo in the RCTs, and pegloticase in the OLE. Tophus response, a secondary endpoint in the trials, was evaluated two ways. Overall tophus CR was the proportion of patients achieving a best response of CR (without any new/enlarging tophi) and target tophus complete response (TT-CR) was the proportion of all tophi with CR.
Among 212 patients randomized in the RCTs, 155 (73%) had ≥ 1 tophus and 547 visible tophi were recorded at baseline. Overall tophus CR was recorded in 45% of patients in the biweekly group (P = 0.002 versus placebo), 26% in the monthly group, and 8% in the placebo group after six months of RCT therapy. TT-CR rates at six months were 28%, 19%, and 2% of tophi, respectively. Patients meeting the primary endpoint of sustained urate-lowering response to therapy (responders) were more likely than nonresponders to have an overall tophus CR at six months (54% vs 20%, respectively and 8% with placebo).
Pegloticase reduced tophus burden in patients with refractory tophaceous gout, especially those achieving sustained urate-lowering. Complete resolution of tophi occurred in some patients by 13 weeks and in others with longer-term therapy.
NCT00325195, NCT01356498.
两项复制的随机、安慰剂对照的六个月试验（RCT）和一个开放标签治疗扩展（OLE）组成了聚乙二醇尿酸酶治疗难治性痛风患者的开发项目。在 RCT 中，接受批准剂量治疗的约 40%的患者至少有一个痛风石完全缓解（CR）。在这里，我们描述了痛风石缓解的时间过程、多发性痛风石患者的总痛风石负担、基线时痛风石大小以及痛风石反应与尿酸降低疗效之间的关系。
在接受聚乙二醇尿酸酶（8mg 每两周或每月）或安慰剂的 RCT 以及 OLE 中，使用计算机辅助数字图像对接受聚乙二醇尿酸酶治疗的患者的皮下痛风石进行了定量分析。作为试验的次要终点，痛风石反应以两种方式进行评估。整体痛风石 CR 是达到最佳 CR 反应（没有任何新的/增大的痛风石）的患者比例，而目标痛风石完全缓解（TT-CR）是达到 CR 的所有痛风石的比例。
在 RCT 中随机分配的 212 名患者中，有 155 名（73%）有≥1个痛风石，基线时有 547 个可见痛风石。在 RCT 治疗六个月后，每两周组有 45%的患者记录到整体痛风石 CR（P=0.002 与安慰剂相比），每月组有 26%，安慰剂组有 8%。六个月时 TT-CR 率分别为 28%、19%和 2%的痛风石。达到治疗尿酸持续降低反应的主要终点（应答者）的患者比未应答者更有可能在六个月时出现整体痛风石 CR（分别为 54%和 20%，安慰剂组为 8%）。
聚乙二醇尿酸酶降低了难治性痛风石性痛风患者的痛风石负担，尤其是那些持续降低尿酸的患者。在 13 周时，一些患者的痛风石完全缓解，而其他患者则需要长期治疗。
NCT00325195，NCT01356498。
