Background & Aims

It is not clear whether concomitant therapy with corticosteroids and anti-tumor necrosis factor (TNF) agents is more effective at inducing remission in patients with Crohn’s disease (CD) than anti-TNF monotherapy. We aimed to determine whether patients with active CD receiving corticosteroids during induction therapy with anti-TNF agents had higher rates of clinical improvement than patients not receiving corticosteroids during induction therapy.

Methods

We systematically searched the MEDLINE, Embase, and CENTRAL databases, through January 20, 2016, for randomized trials of anti-TNF agents approved for treatment of CD and identified 14 trials (5 of adalimumab, 5 of certolizumab, and 4 of infliximab). We conducted a pooled meta-analysis of individual patient and aggregated data from these trials. We compared data from participants who continued oral corticosteroids during induction with anti-TNF therapy to those treated with anti-TNF agents alone. The endpoints were clinical remission (CD activity index [CDAI] scores <150) and clinical response (a decrease in CDAI of 100 points) at the end of induction (weeks 4–14 of treatment).

Results

We included 4354 patients who received induction therapy with anti-TNF agents, including 1653 [38.0%] who were receiving corticosteroids. The combination of corticosteroids and an anti-TNF agent induced clinical remission in 32.0% of patients, whereas anti-TNF monotherapy induced clinical remission in 35.5% of patients (odds ratio [OR], 0.93; 95% CI, 0.74–1.17). The combination of corticosteroids and an anti-TNF agent induced a clinical response in 42.7% of patients, whereas anti-TNF monotherapy induced a clinical response in 46.8% (OR 0.84; 95% CI, 0.73–0.96). These findings did not change with adjustment for baseline CDAI scores and concurrent use of immunomodulators.

Conclusions

Based on a meta-analysis of data from randomized trials of anti-TNF therapies in patients with active CD, patients receiving corticosteroids during induction therapy with anti-TNF agents did not have higher rates of clinical improvement compared with patients not receiving corticosteroids during induction therapy. Given these findings and the risks of corticosteroid use, clinicians should consider early weaning of corticosteroids during induction therapy with anti-TNF agents for patients with corticosteroid-refractory CD.

中文翻译：

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类固醇和肿瘤坏死因子拮抗剂联合治疗诱导克罗恩病患者缓解的效果：系统评价和汇总荟萃分析。

背景与目标

目前尚不清楚皮质类固醇和抗肿瘤坏死因子 (TNF) 药物的联合治疗是否比抗 TNF 单药治疗更能有效地诱导克罗恩病 (CD) 患者的缓解。我们旨在确定在抗 TNF 药物诱导治疗期间接受皮质类固醇的活动性 CD 患者是否比在诱导治疗期间未接受皮质类固醇的患者具有更高的临床改善率。

方法

我们系统地检索了 MEDLINE、Embase 和 CENTRAL 数据库，截至 2016 年 1 月 20 日，寻找批准用于治疗 CD 的抗 TNF 药物的随机试验，并确定了 14 项试验（阿达木单抗 5 项、塞妥珠单抗 5 项和英夫利昔单抗 4 项）。我们对个体患者和这些试验的汇总数据进行了汇总荟萃分析。我们比较了在抗 TNF 治疗诱导期间继续口服皮质类固醇的参与者与仅接受抗 TNF 药物治疗的参与者的数据。终点是诱导结束（治疗第 4-14 周）时的临床缓解（CD 活性指数 [CDAI] 评分 <150）和临床反应（CDAI 降低 100 分）。

结果

我们纳入了 4354 名接受抗 TNF 药物诱导治疗的患者，其中 1653 名 [38.0%] 接受了皮质类固醇治疗。皮质类固醇和抗 TNF 药物联合使用可导致 32.0% 的患者临床缓解，而抗 TNF 单药治疗可导致 35.5% 的患者临床缓解（优势比 [OR]，0.93；95% CI，0.74-1.17）。皮质类固醇和抗 TNF 药物的组合在 42.7% 的患者中引起临床反应，而抗 TNF 单药治疗在 46.8% 中引起临床反应（OR 0.84；95% CI，0.73-0.96）。这些发现并没有随着基线 CDAI 评分的调整和免疫调节剂的同时使用而改变。

结论

根据对活动性 CD 患者抗 TNF 治疗随机试验数据的荟萃分析，与诱导治疗期间未接受皮质类固醇的患者相比，在抗 TNF 药物诱导治疗期间接受皮质类固醇的患者临床改善率没有更高. 鉴于这些发现和使用皮质类固醇的风险，临床医生应考虑在皮质类固醇难治性 CD 患者的抗 TNF 药物诱导治疗期间尽早停用皮质类固醇。