Department of Internal Medicine, Division of Rheumatology, Maastricht University Medical Center, P.O. Box 5800, Maastricht, AZ 6202, the Netherlands; Care and Public Health Research Institute (CAPHRI), Maastricht University, Maastricht, the Netherlands; Department of Rheumatology, VieCuri Medical Center, Venlo, the Netherlands.
Section for Biostatistics and Evidence-Based Research, the Parker Institute, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark; Research Unit of Rheumatology, Department of Clinical Research, University of Southern Denmark, Odense University Hospital, Denmark.
Semin Arthritis Rheum. 2022 Oct;56:152049. doi: 10.1016/j.semarthrit.2022.152049. Epub 2022 Jun 15.
To synthesize evidence of the effect of contextual factors (CFs) on efficacy of urate-lowering therapy (ULT) on serum urate (SU) as outcome in gout patients.
Randomised controlled trials (RCTs) from (updated) Cochrane reviews were the starting point. RCTs were included if they explored the role of any CF on efficacy of ULT on SU in gout patients. For CFs with sufficient data (i.e. ≥3 trials), a mixed-effects meta-regression analysis was performed with trial and comparison as random effects, whereas specific CFs were modelled as fixed factors.
Eight RCTs were included. Effect modification by CFs was explored for age, sex, race, renal function, cardiovascular comorbidity, tophi, thiazide-diuretic use, and previous ULT use. Crude data stratified by renal function were available for four trials (36 randomised comparisons), and suitable for meta-analysis. Pooled estimates revealed that gout patients with a normal, mildly-, or moderately impaired renal function were consistently more likely to achieve SU target with ULT compared to control. Among RCTs comparing ULT to placebo (30 comparisons), effects of ULT on achieving SU target were not statistically different for those with normal (OR:66.87;[11.39-392.75]) compared to mildly (OR:28.54;[5.11-159.46]) and moderately (OR:21.45;[3.20-143.64]) impaired renal function, but seemed lower in those with severely impaired (OR:9.13;[0.96-86.97]) renal function. Data were insufficient to draw conclusions on effect modification by other CFs.
Few RCTs report stratified analyses exploring the role of CFs. ULT seemed effective in reaching the SU target in all levels of renal function, though severely impaired renal function appeared to render a slight disadvantage.
综合观察环境因素（CFs）对降尿酸治疗（ULT）在降低痛风患者血清尿酸（SU）疗效的影响。
以（更新） Cochrane 综述中的随机对照试验（RCT）为起点。如果 RCT 探讨了任何 CF 对痛风患者 ULT 降低 SU 疗效的作用，则纳入研究。对于有足够数据（即≥3 项试验）的 CFs，采用混合效应元回归分析，以试验和比较作为随机效应，而特定 CFs 则作为固定效应进行建模。
共纳入 8 项 RCT。对年龄、性别、种族、肾功能、心血管合并症、痛风石、噻嗪类利尿剂使用和既往 ULT 使用等 CF 进行了效应修饰的探索。四项 RCT（36 项随机比较）提供了肾功能分层的原始数据，适合进行荟萃分析。汇总估计显示，与对照组相比，肾功能正常、轻度或中度受损的痛风患者更有可能通过 ULT 达到 SU 目标。在比较 ULT 与安慰剂的 RCT 中（30 项比较），正常肾功能组（OR：66.87；[11.39-392.75]）与轻度肾功能组（OR：28.54；[5.11-159.46]）和中度肾功能组（OR：21.45；[3.20-143.64]）的 ULT 对达到 SU 目标的疗效差异无统计学意义，但在肾功能严重受损组（OR：9.13；[0.96-86.97]）中似乎较低。数据不足以得出其他 CF 效应修饰的结论。
少数 RCT 报告了分层分析，探索 CFs 的作用。ULT 在所有肾功能水平上似乎都能有效达到 SU 目标，尽管严重肾功能受损似乎略有不利。
