Division of Gastroenterology, University of California, San Diego, La Jolla, California, USA.
Robarts Clinical Trials Inc., London, Ontario, Canada.
Am J Gastroenterol. 2019 May;114(5):733-745. doi: 10.14309/ajg.0000000000000111.
Histologic remission is a potentially valuable means of assessing disease activity and treatment response in ulcerative colitis (UC). However, the efficacy of existing therapies to achieve this outcome is unclear. We performed a systematic review and meta-analysis of histologic outcomes in UC randomized controlled trials and examined the relationship between histologic and endoscopic outcomes.
MEDLINE, EMBASE, CENTRAL, and the Cochrane IBD Register were searched for randomized controlled trials of aminosalicylates, corticosteroids, immunosuppressives, biologics, and small molecules. Histologic and endoscopic remission and response data were independently extracted and pooled using binomial-normal random-effect or fixed-effect models. Pooled efficacy estimates were calculated as risk ratios (RRs) using the Mantel-Haenszel method. Univariable and multivariable random-effect meta-regression models examined factors associated with histologic remission.
Seventy-four studies (68 induction and 7 maintenance) were identified. Topical aminosalicylate enemas [37.2%, 95% confidence interval (CI), 29.0-46.3] and suppositories (44.9%, 95% CI, 28.9-62.3) had the highest induction of histologic remission rates. Aminosalicylate enemas (RR = 4.14, 95% CI, 2.35-7.31), aminosalicylate suppositories (RR = 3.94, 95% CI, 1.26-12.32), and budesonide multimatrix (RR = 1.47, 95% CI 1.08-1.99) had higher histologic remission rates than placebo. Data were lacking for biologics and immunosuppressives. The pooled histologic remission rate for placebo in induction studies was 10.4% (95% CI, 7.1-15.2). Histologic and endoscopic remission correlated strongly (r = 0.66; 95% CI, 0.50-0.78). In multivariate analysis of placebo-arm data, less severe clinical disease activity and corticosteroid use were associated with higher histologic remission rates. Similarly, mild clinical disease activity was associated with higher histologic remission rates when active-arm data were analyzed.
Histologic remission rates for current UC treatments ranged from 15.0% to 44.9% according to drug class and patient population with the highest rates observed for topical aminosalicylates. Placebo remission rates were low with relatively narrow CIs. These data provide benchmarks to inform future trial design. Histologic remission is a potential treatment target in clinical practice.
组织学缓解是评估溃疡性结肠炎（UC）疾病活动度和治疗反应的一种潜在有价值的方法。然而，现有治疗方法实现这一结果的疗效尚不清楚。我们对溃疡性结肠炎随机对照试验的组织学结果进行了系统评价和荟萃分析，并研究了组织学和内镜结果之间的关系。
我们检索了 MEDLINE、EMBASE、CENTRAL 和 Cochrane IBD 注册处，以获取氨基水杨酸盐、皮质类固醇、免疫抑制剂、生物制剂和小分子的随机对照试验。独立提取组织学和内镜缓解和反应数据，并使用二项正态随机效应或固定效应模型进行汇总。使用 Mantel-Haenszel 方法计算汇总疗效估计值为风险比（RR）。单变量和多变量随机效应荟萃回归模型研究了与组织学缓解相关的因素。
确定了 74 项研究（68 项诱导和 7 项维持）。局部氨基水杨酸盐灌肠剂[37.2%，95%置信区间（CI），29.0-46.3]和栓剂（44.9%，95%CI，28.9-62.3）具有最高的组织学缓解率。氨基水杨酸盐灌肠剂（RR=4.14，95%CI，2.35-7.31）、氨基水杨酸盐栓剂（RR=3.94，95%CI，1.26-12.32）和布地奈德多基质（RR=1.47，95%CI 1.08-1.99）的组织学缓解率高于安慰剂。生物制剂和免疫抑制剂的数据缺失。诱导研究中安慰剂组的组织学缓解率为 10.4%（95%CI，7.1-15.2）。组织学和内镜缓解具有很强的相关性（r=0.66；95%CI，0.50-0.78）。在安慰剂组数据的多变量分析中，较轻的临床疾病活动度和皮质类固醇的使用与更高的组织学缓解率相关。同样，当分析活性臂数据时，轻度临床疾病活动与更高的组织学缓解率相关。
根据药物类别和患者人群，当前 UC 治疗的组织学缓解率在 15.0%至 44.9%之间，局部氨基水杨酸盐的缓解率最高。安慰剂缓解率较低，置信区间较窄。这些数据为未来的试验设计提供了基准。组织学缓解是临床实践中的一个潜在治疗目标。
