Department of Gastroenterology D112, The IBD Clinic, Herlev Hospital, University of Copenhagen, Borgmester Ib Juuls Vej 1, 2730, Herlev, Denmark.
Cochrane Musculoskeletal Group, University of Southern Denmark, Odense, Denmark.
Drugs. 2023 Jul;83(11):1027-1038. doi: 10.1007/s40265-023-01914-4. Epub 2023 Jun 26.
Budesonide is accepted as first-choice therapy for microscopic colitis (MC); however, symptoms often recur and some patients may be dependent, intolerant, or even fail budesonide. We performed a systematic review and meta-analysis to determine the effectiveness of non-budesonide therapies (thiopurines, bismuth subsalicylate [BSS], bile acid sequestrants [BAS], loperamide and biologics) for MC suggested by international guidelines.
We searched the CENTRAL, MEDLINE, and EMBASE databases from their inception to 18 April 2023 for the above-mentioned therapeutics in MC. We pooled the response and remission rates by medication using a random-effects model.
Twenty-five studies comprising 1475 patients were included in the meta-analysis. Treatment with BSS showed the highest response rate of 75% (95% confidence interval [CI] 0.65-0.83; I = 70.12%), with 50% achieving remission of symptoms (95% CI 0.35-0.65; I = 71.06%). Treatment with tumor necrosis factor (TNF) inhibitors (infliximab and adalimumab) demonstrated a response rate of 73% (95% CI 0.63-0.83; I = 0.00%), with a remission rate of 44% (95% CI 0.32-0.56; I = 0.00%). The response rate for those treated with vedolizumab was similar; 73% responded to treatment (95% CI 0.57-0.87; I = 35.93%), with a remission rate of 56% (95% CI 0.36-0.75; I = 46.30%). Loperamide was associated with response and remission rates of 62% (95% CI 0.43-0.80; I = 92.99%) and 14% (95% CI 0.07-0.25), respectively, whereas BAS use was associated with response and remission rates of 60% (95% CI 0.51-0.68; I = 61.65%) and 29% (95% CI 0.12-0.55), respectively. Finally, the outcomes for thiopurine use were 49% (95% CI 0.27-0.71; I = 81.45%) and 38% (95% CI 0.23-0.54; I = 50.05%), respectively DISCUSSION: The present systematic review and meta-analysis provides rates of effectiveness of non-budesonide therapies for MC based on available data in the field. Studies in the meta-analysis showed a large amount of heterogeneity due to the variability in assessing the clinical effects of intervention between the studies caused by differences in the definitions of response or remission rates between the studies included. This may likely result in overestimating the benefit of a treatment. Furthermore, the number of participants and drug dosages varied, and only a few studies applied disease-specific activity indices. Only one randomized controlled trial (RCT) was identified. All other 24 included studies were either case series or (retrospective) cohort studies, which complicated efforts to perform further sensitivity analyses to adjust for potential confounders and risk of bias. In addition, the overall evidence on the effect of these treatment options was judged as low, mostly due to comparability bias and the observational nature of the available studies, which limited statistically robust comparisons of rates of effectiveness of the different non-budesonide agents ranked against each other. However, our observational findings may inform clinicians regarding the most rational selection of non-budesonide therapies to patients with MC.
PROSPERO protocol #CRD42020218649.
布地奈德被认为是显微镜结肠炎（MC）的首选治疗方法；然而，症状经常复发，一些患者可能依赖、不耐受，甚至对布地奈德无效。我们进行了一项系统评价和荟萃分析，以确定国际指南推荐的非布地奈德治疗方法（硫嘌呤、双水杨酸铋[BSS]、胆汁酸螯合剂[BAS]、洛哌丁胺和生物制剂）对 MC 的疗效。
我们从成立到 2023 年 4 月 18 日，在 CENTRAL、MEDLINE 和 EMBASE 数据库中搜索上述治疗 MC 的药物。我们使用随机效应模型汇总了药物的反应和缓解率。
25 项研究共纳入 1475 名患者，其中包括 BSS 治疗组，其反应率最高，为 75%（95%置信区间[CI]0.65-0.83；I=70.12%），其中 50%的患者症状缓解（95%CI0.35-0.65；I=71.06%）。肿瘤坏死因子（TNF）抑制剂（英夫利昔单抗和阿达木单抗）治疗的反应率为 73%（95%CI0.63-0.83；I=0.00%），缓解率为 44%（95%CI0.32-0.56；I=0.00%）。接受vedolizumab 治疗的患者反应率相似；73%的患者对治疗有反应（95%CI0.57-0.87；I=35.93%），缓解率为 56%（95%CI0.36-0.75；I=46.30%）。洛哌丁胺的反应率和缓解率分别为 62%（95%CI0.43-0.80；I=92.99%）和 14%（95%CI0.07-0.25），而 BAS 的反应率和缓解率分别为 60%（95%CI0.51-0.68；I=61.65%）和 29%（95%CI0.12-0.55）。最后，硫嘌呤的治疗效果分别为 49%（95%CI0.27-0.71；I=81.45%）和 38%（95%CI0.23-0.54；I=50.05%）。
本系统评价和荟萃分析基于该领域现有数据，提供了非布地奈德治疗 MC 的有效性率。由于研究之间评估干预临床效果的差异，导致研究之间的反应或缓解率的定义不同，荟萃分析中的研究显示出大量的异质性。这可能导致治疗效果的高估。此外，参与者的数量和药物剂量不同，只有少数研究应用了特定疾病的活动指数。仅确定了一项随机对照试验（RCT）。所有其他 24 项纳入的研究都是病例系列或（回顾性）队列研究，这使得很难进一步进行敏感性分析，以调整潜在的混杂因素和偏倚风险。此外，由于可比性偏差和现有研究的观察性质，这些治疗选择的有效性证据总体上被评为低质量，这限制了对彼此排名的不同非布地奈德药物的有效性率进行统计学上稳健的比较。然而，我们的观察性发现可能为临床医生提供关于对 MC 患者最合理选择非布地奈德治疗的信息。
PROSPERO 方案#CRD42020218649。
