Background & Aims

The comparative safety of therapies is important to inform relative positioning within the therapeutic algorithm. Tumor necrosis factor α antagonists (anti-TNF) are associated with an increased risk of infections. Whether there is a similar increase with ustekinumab (UST) or tofacitinib has not been established.

Methods

We identified patients with Crohn’s disease or ulcerative colitis from a national commercial health insurance plan in the United States between 2008 and 2019. Infectious outcomes were ascertained for patients newly initiating anti-TNF, UST, or tofacitinib therapy. Cox proportional hazards models were fit in propensity score-weighted cohorts to compare rates between patients treated with UST or tofacitinib and anti-TNF therapy.

Results

Our study included 19,096, 2420, and 305 patients with inflammatory bowel disease initiating anti-TNF, UST, and tofacitinib therapy, respectively. Over follow-up on-treatment, 7% and 44% of anti-TNF patients had infection-related hospitalizations and developed infections, respectively, compared with 4% and 32% of UST patients and 6% and 41% of tofacitinib patients. In the weighted Cox analysis, UST was associated with a significantly lower risk of infection (hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.86–0.99) compared with anti-TNF therapy. There was a trend towards a reduction in infection-related hospitalizations (HR, 0.84; 95% CI, 0.66–1.03). The risk of infections (HR, 0.97; 95% CI, 0.75–1.24) or infection-related hospitalizations (HR, 0.59; 95% CI, 0.27–1.05) were similar between patients on tofacitinib and anti-TNF.

Conclusions

UST is associated with reduced risk of infections compared to anti-TNF biologics in inflammatory bowel disease, whereas no difference was observed between tofacitinib and anti-TNF therapy.

中文翻译：

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与肿瘤坏死因子 α 拮抗剂相比，乌司奴单抗和托法替布治疗炎症性肠病的感染风险

背景与目标

治疗的相对安全性对于告知治疗算法中的相对定位非常重要。肿瘤坏死因子 α 拮抗剂（抗 TNF）与感染风险增加相关。乌特克单抗 (UST) 或托法替尼是否会出现类似的增加尚未确定。

方法

我们从 2008 年至 2019 年间美国国家商业健康保险计划中确定了患有克罗恩病或溃疡性结肠炎的患者。确定了新开始抗 TNF、UST 或托法替布治疗的患者的感染结果。Cox比例风险模型适合倾向评分加权队列，以比较接受UST或托法替布治疗和抗TNF治疗的患者之间的比率。

结果

我们的研究包括分别开始抗 TNF、UST 和托法替布治疗的 19,096、2420 和 305 名炎症性肠病患者。在治疗随访期间，抗 TNF 患者分别有 7% 和 44% 因感染住院并出现感染，而 UST 患者为 4% 和 32%，托法替布患者为 6% 和 41%。在加权 Cox 分析中，与抗 TNF 治疗相比，UST 与显着降低的感染风险相关（风险比 [HR]，0.93；95% 置信区间 [CI]，0.86–0.99）。与感染相关的住院治疗呈减少趋势（HR，0.84；95% CI，0.66-1.03）。托法替布和抗 TNF 治疗患者之间的感染风险（HR，0.97；95% CI，0.75-1.24）或感染相关住院风险（HR，0.59；95% CI，0.27-1.05）相似。

结论

与炎症性肠病中的抗 TNF 生物制剂相比，UST 与感染风险降低相关，而托法替布和抗 TNF 治疗之间没有观察到差异。