系统评价和网络荟萃分析：中重度克罗恩病的一线和二线生物治疗。
Systematic review and network meta-analysis: first- and second-line biologic therapies for moderate-severe Crohn's disease.
机构信息
Division of Gastroenterology, University of California San Diego, La Jolla, CA, USA.
Division of Biomedical Informatics, University of California San Diego, La Jolla, CA, USA.
出版信息
Aliment Pharmacol Ther. 2018 Aug;48(4):394-409. doi: 10.1111/apt.14852. Epub 2018 Jun 19.
BACKGROUND
There are limited data to inform positioning of agents for treating moderate-severe Crohn's disease (CD).
AIM
We assessed comparative efficacy and safety of first-line (biologic-naïve) and second-line (prior exposure to anti-tumour necrosis factor [TNF]-α) agents) biologic therapy for moderate-severe CD, through a systematic review and network meta-analysis, and appraised quality of evidence (QoE) using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
METHODS
We identified randomised controlled trials (RCTs) in adults with moderate-severe CD treated with approved anti-TNF agents, anti-integrin agents and anti-IL12/23 agents, first-line or second-line, and compared with placebo or another active agent. Efficacy outcomes were induction and maintenance of clinical remission; safety outcomes were serious adverse events and infections. Network meta-analyses were performed, and ranking was assessed using surface under the cumulative ranking (SUCRA) probabilities.
RESULTS
No head-to-head trials were identified. In biologic-naïve patients, infliximab (SUCRA,0.93) and adalimumab (SUCRA,0.75) were ranked highest for induction of clinical remission (moderate QoE). In patients with prior anti-TNF exposure, adalimumab (SUCRA, 0.91; low QoE, in patients with prior response or intolerance to anti-TNF agents) and ustekinumab (SUCRA, 0.71) were ranked highest for induction of clinical remission. In patients with response to induction therapy, adalimumab (SUCRA, 0.97) and infliximab (SUCRA, 0.68) were ranked highest for maintenance of remission. Ustekinumab had lowest risk of serious adverse events (SUCRA, 0.72) and infection (SUCRA, 0.71; along with infliximab, SUCRA, 0.83) in maintenance trials.
CONCLUSION
Indirect comparisons suggest that infliximab or adalimumab may be preferred first-line agents, and ustekinumab a preferred second-line agent, for induction of remission in patients with moderate-severe CD. Head-to-head trials are warranted.
背景
目前针对中重度克罗恩病（CD）的治疗药物，相关定位数据十分有限。
目的
我们通过系统评价和网络荟萃分析，评估了中重度 CD 一线（生物初治）和二线（先前使用过抗 TNF-α 药物）生物治疗药物的疗效和安全性，并采用推荐评估、制定与评价（GRADE）方法评估证据质量（QoE）。
方法
我们检索了成人中重度 CD 患者接受获批的抗 TNF、抗整合素和抗 IL12/23 药物治疗的随机对照试验（RCT），分为一线或二线治疗，并与安慰剂或其他活性药物进行比较。疗效结局包括诱导和维持临床缓解；安全性结局包括严重不良事件和感染。进行了网络荟萃分析，并使用累积排序概率（SUCRA）评估排名。
结果
未发现头对头试验。在生物初治患者中，英夫利昔单抗（SUCRA，0.93）和阿达木单抗（SUCRA，0.75）在诱导临床缓解方面排名最高（中等 QoE）。在先前使用过 TNF 抑制剂的患者中，阿达木单抗（SUCRA，0.91；低 QoE，先前对 TNF 抑制剂有反应或不耐受的患者）和乌司奴单抗（SUCRA，0.71）在诱导临床缓解方面排名最高。在诱导治疗有反应的患者中，阿达木单抗（SUCRA，0.97）和英夫利昔单抗（SUCRA，0.68）在维持缓解方面排名最高。乌司奴单抗在维持试验中严重不良事件（SUCRA，0.72）和感染（SUCRA，0.71；与英夫利昔单抗联合，SUCRA，0.83）风险最低。
结论
间接比较表明，英夫利昔单抗或阿达木单抗可能是中重度 CD 患者诱导缓解的首选一线药物，乌司奴单抗可能是二线首选药物。需要开展头对头试验。
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