Supplementary Material for: Does the 5-Aminosalicylate Concentration Correlate with the Efficacy of Oral 5-Aminosalicylate and Predict Response in Patients with Inflammatory Bowel Disease? A Systematic Review

<b><i>Background:</i></b> Oral 5-aminosalicylic acid (5-ASA, mesalazine) is the first choice therapeutic agent for treating mild-to-moderate ulcerative colitis (UC). Unfortunately a significant group of patients fail to respond. Therapeutic drug monitoring might help to maintain or induce remission by providing a tool for optimization of 5-ASA therapy. However, plasma and urine concentrations of 5-ASA reflect systemic uptake and are not useful to evaluate therapeutic effect. <b><i>Objectives:</i></b> To explore if mucosal and faecal 5-ASA values correlate with disease activity and/or therapeutic effects in patients with inflammatory bowel disease, especially UC. <b><i>Method:</i></b> We identified studies that analysed 5-ASA in faeces or mucosa of humans using an oral 5-ASA formulation, using PubMed and Embase. <b><i>Results:</i></b> In total, 39 studies (<i>n</i> = 939) were included, 27 on faecal 5-ASA, 9 on mucosal concentrations, and 3 on both faecal and mucosal values. We included 33 cross-sectional studies, 3 randomised clinical trials, 2 longitudinal cohorts and 1 randomized cross-over study. Mucosal 5-ASA concentrations in healthy subjects and patients on equivalent doses of 5-ASA were not found to differ remarkably. In the sub-analysis of mucosal 5-ASA concentrations in patients with active or quiescent UC, a higher concentration was seen during remission. Faecal concentrations were associated with 5-ASA doses but not with disease activity. Differences in faecal or mucosal 5-ASA values could not be ascribed to different 5-ASA formulations. <b><i>Conclusions:</i></b> An increase of the mucosal 5-ASA concentrations was observed during remission in patients with UC. No clear relationship between the faecal 5-ASA excretion and the therapeutic efficacy was identified.

背景：口服5-氨基水杨酸（5-aminosalicylic acid，5-ASA，美沙拉嗪（mesalazine））是轻中度溃疡性结肠炎（ulcerative colitis, UC）的首选治疗药物。遗憾的是，有相当比例的患者对其应答不佳。治疗药物监测或许可通过优化5-ASA治疗方案，帮助维持或诱导疾病缓解。然而，5-ASA的血浆及尿液浓度仅能反映全身摄取情况，无法用于评估治疗效果。

目标：旨在探讨炎症性肠病患者的黏膜与粪便5-ASA水平是否与疾病活动度及/或治疗效果相关，尤其针对溃疡性结肠炎患者。

方法：本研究通过PubMed及Embase数据库，检索了采用口服5-ASA制剂并检测人类粪便或黏膜组织中5-ASA水平的相关研究。

结果：最终纳入39项研究（共939例受试者），其中27项针对粪便5-ASA水平、9项针对黏膜5-ASA浓度，另有3项同时检测了粪便与黏膜5-ASA数值。纳入的研究类型包括33项横断面研究、3项随机临床试验、2项纵向队列研究及1项随机交叉研究。在等效剂量5-ASA治疗下，健康受试者与患者的黏膜5-ASA浓度无显著差异。针对活动期或缓解期溃疡性结肠炎患者的黏膜5-ASA浓度亚组分析显示，缓解期患者的黏膜5-ASA浓度更高。粪便5-ASA浓度与给药剂量相关，但与疾病活动度无关联。不同5-ASA制剂并未导致粪便或黏膜5-ASA水平出现差异。

结论：溃疡性结肠炎患者在疾病缓解期的黏膜5-ASA浓度升高。未发现粪便5-ASA排泄量与治疗疗效之间存在明确关联。