皮质类固醇药物对托法替布诱导溃疡性结肠炎缓解疗效及感染发生率的影响。

Impact of Concomitant Corticosteroids on Tofacitinib Induction Efficacy and Infection Rates in Ulcerative Colitis.

机构信息

Division of Gastroenterology, Perelman School of Medicine of the University of Pennsylvania, Philadelphia, PA, USA.

Department of Gastroenterology, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA.

出版信息

Dig Dis Sci. 2023 Jun;68(6):2624-2634. doi: 10.1007/s10620-022-07794-0. Epub 2023 Feb 4.

DOI:10.1007/s10620-022-07794-0

PMID:36739367

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9899108/

Abstract

BACKGROUND

Tofacitinib is an oral small molecule Janus kinase inhibitor for the treatment of ulcerative colitis.

AIM

To report efficacy and infection rates in patients receiving tofacitinib induction treatment, by baseline corticosteroid status.

METHODS

We evaluated efficacy and safety data from OCTAVE Induction 1&2 in patients with moderately-to-severely active ulcerative colitis who received tofacitinib 10 mg twice daily or placebo for 8 weeks, based on induction baseline oral corticosteroid use (Corticosteroid-Yes/No) and dose (< 20/ ≥ 20 mg/day). Infections of interest included serious infections, herpes zoster (HZ), and adjudicated opportunistic infections (OIs).

RESULTS

At OCTAVE Induction 1&2 baseline, 478/1092 (43.8%) patients were receiving corticosteroids. Tofacitinib demonstrated significant induction efficacy versus placebo for both Corticosteroid-Yes and Corticosteroid-No. With adjustment for prior tumor necrosis factor inhibitor and immunosuppressant failure, there were no statistically significant differences in remission and clinical response rates for Corticosteroid-Yes versus Corticosteroid-No. Among tofacitinib-treated patients, HZ and OIs occurred more frequently in Corticosteroid-Yes versus Corticosteroid-No, regardless of dose (< 20 mg vs. ≥ 20 mg). Infection incidence rates (regardless of severity/seriousness) during tofacitinib induction were generally similar regardless of baseline corticosteroid use. The proportion of tofacitinib-treated patients with HZ was 0.2% for Corticosteroid-No versus 1.1% for Corticosteroid-Yes < 20 mg and 1.0% for Corticosteroid-Yes ≥ 20 mg. Two out of three patients had HZ OIs.

CONCLUSIONS

Tofacitinib induction efficacy (clinical response and remission) was similar in baseline corticosteroid subgroups. Infections of interest were rare; HZ and OIs occurred more frequently among those receiving tofacitinib and corticosteroids versus those receiving tofacitinib without corticosteroids.

TRIAL REGISTRATION

http://www.

CLINICALTRIALS

gov (NCT01465763[21/10/2011]; NCT01458951[21/10/2011]).

摘要

背景

托法替尼是一种用于治疗溃疡性结肠炎的口服小分子 Janus 激酶抑制剂。

目的

报告根据基线皮质类固醇状态接受托法替尼诱导治疗的患者的疗效和感染率。

方法

我们评估了 OCTAVE Induction 1&2 中接受托法替尼 10mg 每日两次或安慰剂治疗 8 周的中重度溃疡性结肠炎患者的疗效和安全性数据，这些患者根据诱导基线口服皮质类固醇的使用（皮质类固醇-是/否）和剂量（<20/≥20mg/天）。感兴趣的感染包括严重感染、带状疱疹（HZ）和经裁决的机会性感染（OI）。

结果

在 OCTAVE Induction 1&2 的基线时，478/1092（43.8%）名患者正在接受皮质类固醇治疗。托法替尼与安慰剂相比，在皮质类固醇-是和皮质类固醇-否的患者中均显示出显著的诱导疗效。在调整了先前肿瘤坏死因子抑制剂和免疫抑制剂失败的情况下，皮质类固醇-是与皮质类固醇-否的缓解和临床反应率没有统计学上的显著差异。在接受托法替尼治疗的患者中，无论剂量（<20mg 与≥20mg）如何，HZ 和 OI 在皮质类固醇-是患者中的发生率均高于皮质类固醇-否患者。在托法替尼诱导期间，无论严重程度如何，感染发生率（无论严重程度如何）在皮质类固醇使用的基础上基本相似。皮质类固醇-否的托法替尼治疗患者中，HZ 的比例为 0.2%，皮质类固醇-否<20mg 的患者为 1.1%，皮质类固醇-是≥20mg 的患者为 1.0%。三分之二的患者发生 HZ OI。