Inflammatory Bowel Disease Center, Department of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL, USA.
Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA.
Aliment Pharmacol Ther. 2021 Aug;54(4):429-440. doi: 10.1111/apt.16439. Epub 2021 Jun 24.
Obesity may affect efficacy and safety of biologic treatments for ulcerative colitis (UC). Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of UC.
To assess efficacy and safety of tofacitinib in patients with UC, by baseline body mass index (BMI).
This post hoc analysis evaluated patients with UC receiving placebo or tofacitinib from the 8-week OCTAVE Induction 1 and 2 (NCT01465763, NCT01458951) and 52-week OCTAVE Sustain (NCT01458574) studies. Patients were stratified by BMI at OCTAVE Induction 1 and 2 baseline (<25, 25 to <30 and ≥30 kg/m ). Outcomes included remission, endoscopic improvement, clinical response, sustained steroid-free remission, Inflammatory Bowel Disease Questionnaire total score and Short Form-36 Health Survey scores. Adverse events were evaluated.
At Week 8 of OCTAVE Induction 1 and 2, and Week 52 of OCTAVE Sustain, higher proportions of patients receiving tofacitinib 5 or 10 mg twice daily (b.d.) achieved clinical response vs placebo, regardless of baseline BMI subgroup (all P < 0.05). Proportions of patients achieving efficacy endpoints were generally similar across BMI subgroups; in univariate and multivariate regression analyses, BMI was not a significant predictor (all P ≥ 0.05; univariate BMI [continuous] odds ratio for remission: 0.98 [95% confidence interval 0.95, 1.02]). There was no consistent trend between BMI and adverse events. Among patients receiving tofacitinib 10 mg b.d. in OCTAVE Induction 1 and 2, serious infections were numerically greater in the BMI ≥30 subgroup (3.2%) vs other subgroups (0.4%). Limitations included small patient numbers in the BMI ≥30 subgroup.
Efficacy and safety of tofacitinib were similar in patients with UC regardless of baseline BMI.
肥胖可能会影响溃疡性结肠炎（UC）生物治疗的疗效和安全性。托法替尼是一种用于治疗 UC 的口服小分子 Janus 激酶抑制剂。
通过基线体重指数（BMI）评估 UC 患者接受托法替尼治疗的疗效和安全性。
本事后分析评估了来自 OCTAVE 诱导 1 和 2 期（NCT01465763，NCT01458951）和 52 周 OCTAVE 维持（NCT01458574）研究的接受安慰剂或托法替尼治疗的 UC 患者。患者根据 OCTAVE 诱导 1 和 2 期基线时的 BMI 分层（<25、25 至<30 和≥30kg/m2）。结局包括缓解、内镜改善、临床应答、持续无激素缓解、炎症性肠病问卷总评分和健康调查简表 36 项评分。评估了不良事件。
在 OCTAVE 诱导 1 和 2 期的第 8 周和 OCTAVE 维持的第 52 周，接受托法替尼 5 或 10mg 每日 2 次（b.d.）治疗的患者与安慰剂相比，临床应答比例更高，无论基线 BMI 亚组如何（均 P<0.05）。在各个 BMI 亚组中，达到疗效终点的患者比例通常相似；在单变量和多变量回归分析中，BMI 不是显著的预测因素（均 P≥0.05；单变量 BMI[连续]缓解的比值比：0.98[95%置信区间 0.95，1.02]）。BMI 与不良事件之间没有一致的趋势。在 OCTAVE 诱导 1 和 2 期接受托法替尼 10mg b.d.治疗的患者中，BMI≥30 亚组（3.2%）与其他亚组（0.4%）相比，严重感染的发生率更高。局限性包括 BMI≥30 亚组的患者人数较少。
无论 UC 患者的基线 BMI 如何，托法替尼的疗效和安全性相似。
