Thiopurines are proven agents in the treatment of Crohn’s disease. While pancreatitis is recognised as an adverse event associated with therapy, the effect size and morbidity of thiopurine-induced pancreatitis is not known. The aim of this systematic review and meta-analysis was to quantify the risk of pancreatitis with azathioprine and 6-mercaptopurine (6-MP) within Crohn’s disease. We searched six electronic databases from inception to 29 October 2019. The primary outcomes measures were the occurrence of pancreatitis. We calculated pooled OR with corresponding 95% CIs for risk of pancreatitis. A number needed to harm analysis was performed. The search identified 4418 studies, of which 25 randomised controlled trials met the criteria for inclusion. The number of patients treated with azathioprine to cause an episode of pancreatitis was 36 (induction of remission) and 31 (maintenance of remission).The risk of pancreatitis in patients receiving azathioprine across all contexts was 3.80%, compared with a control risk of 0.2% (placebo) and 0.5% (5-aminosalicylic acid agents). There was no difference seen between 6-MP and placebo, although this was a low certainty result due to imprecision from very low event numbers and patient numbers. There is a probably increased occurrence of pancreatitis when azathioprine is used in Crohn’s disease (moderate certainty), with incidence overall approximately 3.8%. Most cases are mild and resolve on cessation of therapy and no mortality was reported. There was no increased occurrence seen when using 6-MP, although this is a low certainty finding. PROSPERO prior to the study (CRD42019138065).

中文翻译：

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克罗恩病中与硫唑嘌呤和 6-巯基嘌呤使用相关的胰腺炎：系统评价

硫嘌呤是治疗克罗恩病的有效药物。虽然胰腺炎被认为是与治疗相关的不良事件，但硫嘌呤诱导的胰腺炎的影响大小和发病率尚不清楚。本系统评价和荟萃分析的目的是量化克罗恩病中使用硫唑嘌呤和 6-巯基嘌呤 (6-MP) 的胰腺炎风险。我们检索了从成立到 2019 年 10 月 29 日的六个电子数据库。主要结局指标是胰腺炎的发生率。我们计算了胰腺炎风险的合并 OR 和相应的 95% CI。进行了伤害分析所需的数量。搜索确定了 4418 项研究，其中 25 项随机对照试验符合纳入标准。接受硫唑嘌呤治疗导致胰腺炎发作的患者人数为 36 人（诱导缓解）和 31 人（维持缓解）。在所有情况下接受硫唑嘌呤的患者发生胰腺炎的风险为 3.80%，而控制风险为 0.2 %（安慰剂）和 0.5%（5-氨基水杨酸剂）。6-MP 和安慰剂之间没有发现差异，尽管由于非常低的事件数和患者数的不精确性，这是一个低确定性的结果。当硫唑嘌呤用于克罗恩病时，胰腺炎的发生率可能会增加（中等确定性），总体发病率约为 3.8%。大多数病例是轻微的并且在停止治疗后消退，并且没有死亡报告。使用 6-MP 时发生率没有增加，尽管这是一个低确定性的发现。