Background & Aims

There is debate over whether patients with inflammatory bowel diseases (IBD) treated with biologics that are not tumor necrosis factor antagonists (such as vedolizumab or ustekinumab) should receive concomitant treatment with immunomodulators. We conducted a meta-analysis to compare the efficacy and safety of concomitant immunomodulator therapy vs vedolizumab or ustekinumab monotherapy.

Methods

In a systematic search of publications, through July 31, 2019, we identified 33 studies (6 randomized controlled trials and 27 cohort studies) of patients with IBD treated with vedolizumab or ustekinumab. The primary outcome was clinical benefit, including clinical remission, clinical response, or physician global assessment in patients who did vs did not receive combination therapy with an immunomodulator. Secondary outcomes were endoscopic improvement and safety. We performed random-effects meta-analysis and estimated odds ratio (OR) and 95% CIs.

Results

Overall, combination therapy was not associated with better clinical outcomes in patients receiving vedolizumab (16 studies: OR, 0.84; 95% CI, 0.68–1.05; I2=13.9%; Q test P = .17) or ustekinumab (15 studies: OR, 1.1; 95% CI, 0.87–1.38; I2 = 11%; Q test P = .28). Results were consistent in subgroup analyses, with no difference in clinical remission or response in induction vs maintenance studies or in patients with Crohn’s disease vs ulcerative colitis in studies of vedolizumab. Combination therapy was not associated with better endoscopic outcomes in patients receiving vedolizumab (3 studies: OR, 1.13; 95% CI, 0.48–2.68; I2 = 0; Q test P=.96) or ustekinumab (2 studies: OR, 0.58; 95% CI, 0.21–1.16; I2 = 47%; Q test P = .17). Combination therapy was not associated with an increase in adverse events during vedolizumab therapy (4 studies: OR, 1.17; 95% CI, 0.75–1.84; I2 = 0; Q test P = .110).

Conclusions

In a meta-analysis of data from studies of patients with IBD, we found that combining vedolizumab or ustekinumab with an immunomodulator is no more effective than monotherapy in induction or maintenance of remission.

中文翻译：

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联合免疫调节剂治疗对炎症性肠病患者非肿瘤坏死因子拮抗剂的生物制剂的疗效没有益处：一项荟萃分析

背景与目标

对于接受非肿瘤坏死因子拮抗剂生物制剂（如维多珠单抗或优特克单抗）治疗的炎症性肠病 (IBD) 患者是否应同时接受免疫调节剂治疗存在争议。我们进行了一项荟萃分析，以比较联合免疫调节剂治疗与维多珠单抗或优特克单抗单药治疗的疗效和安全性。

方法

在对出版物的系统检索中，截至 2019 年 7 月 31 日，我们确定了 33 项研究（6 项随机对照试验和 27 项队列研究），其中 IBD 患者接受了维多珠单抗或优特克单抗治疗。主要结果是临床获益，包括接受与未接受免疫调节剂联合治疗的患者的临床缓解、临床反应或医师整体评估。次要结果是内窥镜改善和安全性。我们进行了随机效应荟萃分析和估计优势比 (OR) 和 95% CI。

结果

总体而言，在接受维多珠单抗（16 项研究：OR，0.84；95% CI，0.68–1.05；I2=13.9%；Q 检验 P = .17）或优特克单抗（15 项研究：OR , 1.1；95% CI, 0.87–1.38；I2 = 11%；Q 检验 P = .28)。结果在亚组分析中是一致的，在 vedolizumab 的研究中，诱导与维持研究或克罗恩病与溃疡性结肠炎患者的临床缓解或反应没有差异。在接受维多珠单抗（3 项研究：OR，1.13；95% CI，0.48-2.68；I2 = 0；Q 检验 P=0.96）或优特克单抗（2 项研究：OR，0.58； 95% CI，0.21–1.16；I2 = 47%；Q 检验 P = .17)。联合治疗与维多珠单抗治疗期间不良事件的增加无关（4 项研究：OR，1.17；95% CI，0.75–1.84；I2 = 0; Q 检验 P = .110)。

结论

在对 IBD 患者研究数据的荟萃分析中，我们发现将维多珠单抗或优特克单抗与免疫调节剂联合使用在诱导或维持缓解方面并不比单一疗法更有效。