接受托法替尼治疗的溃疡性结肠炎患者疱疹感染的长期风险。
Long-term Risk of Herpes Zoster Infection in Patients With Ulcerative Colitis Receiving Tofacitinib.
机构信息
Oregon Health & Science University, Portland, Oregon, USA.
Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium.
出版信息
Inflamm Bowel Dis. 2023 Jan 5;29(1):85-96. doi: 10.1093/ibd/izac063.
BACKGROUND
Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). We report herpes zoster (HZ) incidence and risk factors in the tofacitinib UC clinical program (up to 7.8 years).
METHODS
Proportions and incidence rates (IRs; unique patients with events/100 patient-years) of HZ were evaluated in 4 cohorts: Induction (phase 2 and 3 induction study data), Maintenance (phase 3 maintenance study data), Overall (data from all phase 2, 3, and open-label, long-term extension studies), and Overall plus interim 6-month phase 3b and 4 data. Herpes zoster risk factors were assessed by Cox regression analysis.
RESULTS
In the Induction and Maintenance Cohorts, IRs for HZ (nonserious and serious) were numerically higher with tofacitinib 10 mg twice daily (BID) vs placebo and tofacitinib 10 vs 5 mg BID, respectively. With all tofacitinib doses (5 or 10 mg BID), IRs (95% confidence intervals) for HZ in the Overall and Overall plus phase 3b/4 Cohorts (total exposure, 2814.4 and 2999.7 patient-years, respectively) were 3.38 (2.73-4.15) and 3.30 (2.67-4.04), respectively. In the Overall plus phase 3b/4 Cohort, >90% of HZ were nonserious; >90% were mild/moderate; >90% resolved without discontinuing tofacitinib; 0.6% of patients had multiple HZ events. Herpes zoster IRs were stable when analyzed by 6-month intervals up to >30 months. Herpes zoster risk factors included older age, lower weight, geographic region, and prior tumor necrosis factor inhibitor (TNFi) failure.
CONCLUSIONS
Most HZ events were mild/moderate. Herpes zoster IRs remained stable over 7.8 years of exposure. Older age, lower weight, geographic region, and prior TNFi failure were associated with increased HZ risk.
CLINICALTRIALS.GOV: NCT00787202;NCT01465763;NCT01458951;NCT01458574;NCT01470612;NCT03281304.
背景
托法替布是一种用于治疗溃疡性结肠炎（UC）的口服小分子 Janus 激酶抑制剂。我们报告了托法替布 UC 临床项目（最长 7.8 年）中带状疱疹（HZ）的发病率和危险因素。
方法
在 4 个队列中评估了 HZ 的比例和发病率（IR；每 100 名患者中有事件的独特患者/年）：诱导期（2 期和 3 期诱导研究数据）、维持期（3 期维持研究数据）、总体（来自所有 2 期、3 期和开放标签、长期扩展研究的数据）以及总体加中期 3b 期和 4 期数据。通过 Cox 回归分析评估带状疱疹的危险因素。
结果
在诱导期和维持期队列中，与安慰剂和托法替布 10 毫克相比，托法替布 10 毫克每日两次（BID）的 HZ（非严重和严重）IR 分别呈数值性升高。在所有托法替布剂量（5 或 10 mg BID）下，总体和总体加 3b/4 期队列（总暴露分别为 2814.4 和 2999.7 患者年）的 HZ IR（95%置信区间）分别为 3.38（2.73-4.15）和 3.30（2.67-4.04）。在总体加 3b/4 期队列中，>90%的 HZ 为非严重；>90%为轻度/中度；>90%在不停止托法替布的情况下得到解决；0.6%的患者有多次 HZ 事件。在长达>30 个月的 6 个月间隔分析中，HZ 的 IR 保持稳定。带状疱疹的危险因素包括年龄较大、体重较低、地理位置和既往肿瘤坏死因子抑制剂（TNFi）失败。
结论
大多数 HZ 事件为轻度/中度。在 7.8 年的暴露期间，带状疱疹的 IR 保持稳定。年龄较大、体重较低、地理位置和既往 TNFi 失败与 HZ 风险增加相关。
临床试验.gov：NCT00787202；NCT01465763；NCT01458951；NCT01458574；NCT01470612；NCT03281304。
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