Department of Medicine, University of Otago, Christchurch, Christchurch, New Zealand.
Department of Rheumatology, Immunology and Allergy, Christchurch Hospital, Christchurch, New Zealand.
Ann Rheum Dis. 2017 Sep;76(9):1522-1528. doi: 10.1136/annrheumdis-2016-210872. Epub 2017 Mar 17.
To determine the efficacy and safety of allopurinol dose escalation using a treat-to-target serum urate (SU) approach.
A randomised, controlled, parallel-group, comparative clinical trial was undertaken. People with gout receiving at least creatinine clearance (CrCL)-based allopurinol dose for ≥1 month and SU ≥6 mg/dL were recruited. Participants were randomised to continue current dose (control) or allopurinol dose escalation for 12 months. In the dose escalation group, allopurinol was increased monthly until SU was <6 mg/dL. The primary endpoints were reduction in SU and adverse events (AEs).
183 participants (93 control, 90 dose escalation) were recruited. At baseline, mean (SD) urate was 7.15 (1.6) mg/dL and allopurinol dose 269 mg/day. 52% had CrCL<60 mL/min. Mean changes in SU at the final visit were -0.34 mg/dL in the control group and -1.5 mg/dL in the dose escalation group (p<0.001) with a mean difference of 1.2 mg/dL (95% CI 0.67 to 1.5, p<0.001). At month 12, 32% of controls and 69% in the dose escalation had SU <6 mg/dL. There were 43 serious AEs in 25 controls and 35 events in 22 dose escalation participants. Only one was considered probably related to allopurinol. Five control and five dose escalation participants died; none was considered allopurinol related. Mild elevations in LFTs were common in both groups, a few moderate increases in gamma glutamyl transferase (GGT) were noted. There was no difference in renal function changes between randomised groups.
Higher than CrCL-based doses of allopurinol can effectively lower SU to treatment target in most people with gout. Allopurinol dose escalation is well tolerated.
ANZCTR12611000845932; Results.
确定采用达标治疗（treat-to-target）血清尿酸（SU）方案逐渐增加别嘌醇剂量的疗效和安全性。
进行了一项随机、对照、平行组、比较临床试验。招募了正在接受至少基于肌酐清除率（CrCL）的别嘌醇剂量治疗至少 1 个月且 SU≥6mg/dL 的痛风患者。参与者被随机分为继续当前剂量（对照组）或别嘌醇剂量增加 12 个月。在剂量增加组中，每月增加别嘌醇剂量，直至 SU<6mg/dL。主要终点是 SU 的降低和不良事件（AE）。
共纳入 183 名参与者（对照组 93 名，剂量增加组 90 名）。基线时，尿酸的平均值（标准差）为 7.15（1.6）mg/dL，别嘌醇剂量为 269mg/天。52%的患者 CrCL<60mL/min。对照组最终访视时 SU 的平均变化为-0.34mg/dL，剂量增加组为-1.5mg/dL（p<0.001），平均差异为 1.2mg/dL（95%CI 0.67 至 1.5，p<0.001）。在第 12 个月时，对照组有 32%和剂量增加组有 69%的患者 SU<6mg/dL。对照组有 25 名参与者发生 43 例严重 AE，剂量增加组有 22 名参与者发生 35 例事件。只有 1 例被认为可能与别嘌醇有关。对照组有 5 名参与者和剂量增加组有 5 名参与者死亡；均与别嘌醇无关。两组的肝功能轻度升高都很常见，少数γ谷氨酰转移酶（GGT）中度升高。两组之间肾功能变化无差异。
在大多数痛风患者中，使用高于基于 CrCL 的别嘌醇剂量可以有效降低 SU 至治疗目标。逐渐增加别嘌醇剂量的耐受性良好。
ANZCTR12611000845932；结果。
