Honap Sailish, Meade Susanna, Ibraheim Hajir, Irving Peter M, Jones Michael P, Samaan Mark A
IBD Centre, 1st Floor IBD Centre, Westminster Bridge Road, St Thomas Hospital, Guys and St Thomas NHS Foundation Trust, London, SE1 7EH, UK.
School of Immunology and Microbial Sciences, Kings College London, London, UK.
Dig Dis Sci. 2022 Mar;67(3):1018-1035. doi: 10.1007/s10620-021-06932-4. Epub 2021 Mar 16.
Ustekinumab, an interleukin-12 and interleukin-23 antagonist, is licensed for the treatment of Crohn's disease (CD) and ulcerative colitis (UC) after the phase III trial programs demonstrated efficacy over placebo. However, these findings may not be directly transferable to the real-world due to the stringent inclusion criteria of clinical trials.
We conducted a systematic review and meta-analysis of the safety and effectiveness of ustekinumab in inflammatory bowel disease (IBD). A systematic literature search was conducted via Medline and Embase from inception to April 21, 2020. Observational studies assessing ustekinumab's safety and effectiveness by reporting response, remission and/or adverse events (AE) in either CD or UC were included. Two reviewers independently assessed risk of bias and extracted study data. Random-effects meta-analysis was performed to pool rates of clinical response, remission, and safety data.
Following deduplication, 2147 records were identified of which 41 studies (38 CD, 3 UC) comprising 4400 patients were included for quantitative analysis. Pooled clinical remission rates for CD were 34% (95% CI, 26%-42%) following induction and 31% (95% CI, 25%-38%) at one year. For UC, post-induction clinical remission rates were 39% (95% CI, 23%-56%). Serious AEs were reported in 5.6% of patients. Pregnancy outcomes were similar to the general population. One-third of patients with active baseline perianal disease responded or had fistula healing with ustekinumab.
In the most comprehensive systematic review and meta-analysis to date, and the first to include UC, ustekinumab was shown to be effective and safe in the real-world treatment of IBD.
乌司奴单抗是一种白细胞介素-12和白细胞介素-23拮抗剂，在III期试验项目证明其疗效优于安慰剂后，已获许可用于治疗克罗恩病（CD）和溃疡性结肠炎（UC）。然而，由于临床试验严格的纳入标准，这些研究结果可能无法直接应用于现实世界。
我们对乌司奴单抗在炎症性肠病（IBD）中的安全性和有效性进行了系统评价和荟萃分析。通过检索Medline和Embase数据库，从数据库建立至2020年4月21日进行系统的文献检索。纳入通过报告CD或UC中的缓解、缓解和/或不良事件（AE）来评估乌司奴单抗安全性和有效性的观察性研究。两名评价者独立评估偏倚风险并提取研究数据。采用随机效应荟萃分析汇总临床缓解率、缓解率和安全性数据。
经过去重后，共识别出2147条记录，其中41项研究（38项CD研究，3项UC研究），共4400例患者纳入定量分析。CD诱导治疗后的合并临床缓解率为34%（95%CI，26%-42%），一年时为31%（95%CI，25%-38%）。对于UC，诱导治疗后的临床缓解率为39%（95%CI，23%-56%）。5.6%的患者报告了严重不良事件。妊娠结局与一般人群相似。三分之一基线有活动性肛周疾病的患者对乌司奴单抗有反应或瘘管愈合。
在迄今为止最全面的系统评价和荟萃分析中，也是首次纳入UC的分析中，乌司奴单抗在IBD的现实世界治疗中显示出有效且安全。
