Adimadhyam Sruthi, Lewis James D, Simon Andrew L, Wolfe Audrey E, Smith Samantha, Hou Laura, Moyneur Érick, Reynolds Juliane S, Toh Sengwee, Dobes Angela, Parlett Lauren, Haynes Kevin, Burris Jessica, Dorand Jennifer E, Long Millie D, Kappelman Michael D
Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.
Division of Gastroenterology and Hepatology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Inflamm Bowel Dis. 2024 Apr 3;30(4):554-562. doi: 10.1093/ibd/izad115.
Antitumor necrosis factor (anti-TNF) inhibitors are first-line treatment among patients with ulcerative colitis (UC). With time, patients tend to lose response or become intolerant, necessitating switching to small cell biologics such as tofacitinib or vedolizumab. In this real-world study of a large, geographically diverse US population of TNF-experienced patients with UC, we evaluated the effectiveness and safety of newly initiating treatment with tofacitinib vs vedolizumab.
We conducted a cohort study using secondary data from a large US insurer (Anthem, Inc.). Our cohort included patients with UC newly initiating treatment with tofacitinib or vedolizumab. Patients were required to have evidence of treatment with anti-TNF inhibitors in the 6 months prior to cohort entry. The primary outcome was treatment persistence >52 weeks. Additionally, we evaluated the following secondary outcomes as additional measures of effectiveness and safety: (1) all-cause hospitalization; (2) total abdominal colectomy; (3) hospitalization for infection; (4) hospitalization for malignancy; (5) hospitalization for cardiac events; and (6) hospitalization for thromboembolic events. We used fine stratification by propensity scores to control for confounding by demographics, clinical factors, and treatment history at baseline.
Our primary cohort included 168 new users of tofacitinib and 568 new users of vedolizumab. Tofacitinib was associated with lower treatment persistence (adjusted risked ratio, 0.77; 95% CI, 0.60 -0.99). Differences in secondary measures of effectiveness or safety between tofacitinib initiators vs vedolizumab initiators were not statistically significant (all-cause hospitalization, adjusted hazard ratio, 1.23; 95% CI, 0.83-1.84; total abdominal colectomy, adjusted HR, 1.79; 95% CI, 0.93-3.44;and hospitalization for any infection, adjusted HR, 1.94; 95% CI, 0.83-4.52).
Ulcerative colitis patients with prior anti-TNF experience initiating tofacitinib demonstrated lower treatment persistence compared with those initiating vedolizumab. This finding is in contrast to other recent studies suggesting superior effectiveness of tofacitinib. Ultimately, head-to-head randomized, controlled trials that focus on directly measured end points may be needed to best inform clinical practice.
抗肿瘤坏死因子（抗TNF）抑制剂是溃疡性结肠炎（UC）患者的一线治疗药物。随着时间的推移，患者往往会失去反应或出现不耐受情况，因此需要改用托法替布或维多珠单抗等小分子生物制剂。在这项针对美国大量不同地区、有抗TNF治疗经历的UC患者的真实世界研究中，我们评估了新开始使用托法替布与维多珠单抗治疗的有效性和安全性。
我们使用来自美国一家大型保险公司（Anthem公司）的二次数据进行了一项队列研究。我们的队列包括新开始使用托法替布或维多珠单抗治疗的UC患者。患者在进入队列前6个月内需有抗TNF抑制剂治疗的证据。主要结局是治疗持续时间>52周。此外，我们评估了以下次要结局作为有效性和安全性的额外衡量指标：（1）全因住院；（2）全腹结肠切除术；（3）感染住院；（4）恶性肿瘤住院；（5）心脏事件住院；（6）血栓栓塞事件住院。我们使用倾向评分进行精细分层，以控制基线时人口统计学、临床因素和治疗史的混杂因素。
我们的主要队列包括168名新使用托法替布的患者和568名新使用维多珠单抗的患者。托法替布与较低的治疗持续率相关（调整后的风险比为0.77；95%置信区间为0.60-0.99）。托法替布起始者与维多珠单抗起始者在有效性或安全性次要指标上的差异无统计学意义（全因住院，调整后的风险比为1.23；95%置信区间为0.83-1.84；全腹结肠切除术，调整后的风险比为1.79；95%置信区间为0.93-3.44；任何感染住院，调整后的风险比为1.94；95%置信区间为0.83-4.52）。
有抗TNF治疗经历的溃疡性结肠炎患者开始使用托法替布时，其治疗持续率低于开始使用维多珠单抗的患者。这一发现与其他近期研究表明托法替布具有更高有效性的结果相反。最终，可能需要进行直接针对直接测量终点的头对头随机对照试验，以更好地为临床实践提供依据。
