Sandborn William J, Peyrin-Biroulet Laurent, Sharara Ala I, Su Chinyu, Modesto Irene, Mundayat Rajiv, Gunay L Mert, Salese Leonardo, Sands Bruce E
Division of Gastroenterology, University of California San Diego, La Jolla, California.
Inserm Nutrition, Genetics, and Environmental Risk Exposure U1256, Department of Gastroenterology, Nancy University Hospital, Lorraine University, Vandœuvre lès-Nancy, France.
Clin Gastroenterol Hepatol. 2022 Mar;20(3):591-601.e8. doi: 10.1016/j.cgh.2021.02.043. Epub 2021 Mar 6.
BACKGROUND & AIMS: Tofacitinib is an oral, small-molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). We summarize the efficacy and safety data of tofacitinib 5 or 10 mg twice daily in the UC clinical program, stratified by prior tumor necrosis factor inhibitor (TNFi) failure status.
Efficacy was assessed in the pooled phase 3 OCTAVE Induction 1 and 2 studies (N = 1139), the phase 3 OCTAVE Sustain maintenance study (N = 593), and the dose-escalation subpopulation of the open-label, long-term extension OCTAVE Open study (N = 59). Safety was assessed in OCTAVE Sustain, the dose-escalation subpopulation, and the Overall Cohort, which included patients from OCTAVE Induction 1 and 2, OCTAVE Sustain, and OCTAVE Open (N = 1124; no prior TNFi failure N = 541; prior TNFi failure N = 583; phase 2 data were excluded when stratified by prior TNFi failure status). The dose-escalation subpopulation received tofacitinib 10 mg twice daily in OCTAVE Induction 1 and 2, tofacitinib 5 mg twice daily in OCTAVE Sustain, and tofacitinib 10 mg twice daily in OCTAVE Open.
Tofacitinib had greater efficacy than placebo, regardless of prior TNFi failure status. In OCTAVE Sustain and the Overall Cohort, herpes zoster [HZ] (nonserious and serious) rates were numerically higher in tofacitinib-treated patients with vs without prior TNFi failure. Dose escalation to tofacitinib 10 mg twice daily generally recaptured clinical response for most patients. HZ (nonserious and serious) rates were numerically higher in the dose-escalation subpopulation vs the Overall Cohort.
Tofacitinib was efficacious in patients with UC regardless of prior TNFi failure status. HZ (nonserious and serious) rates were numerically higher in patients who had previously failed TNFi. ClinicalTrials.gov: A3921063 (NCT00787202); OCTAVE Induction 1 (NCT01465763); OCTAVE Induction 2 (NCT01458951); OCTAVE Sustain (NCT01458574); and OCTAVE Open (NCT01470612).
托法替布是一种口服小分子 Janus 激酶抑制剂，用于治疗溃疡性结肠炎（UC）。我们总结了在 UC 临床研究项目中，每日两次服用 5 毫克或 10 毫克托法替布的疗效和安全性数据，并根据既往肿瘤坏死因子抑制剂（TNFi）治疗失败状态进行分层。
在 3 期 OCTAVE 诱导 1 和 2 研究的汇总数据（N = 1139）、3 期 OCTAVE 维持研究（N = 593）以及开放标签、长期扩展 OCTAVE 开放研究的剂量递增亚组（N = 59）中评估疗效。在 OCTAVE 维持研究、剂量递增亚组以及总体队列中评估安全性，总体队列包括来自 OCTAVE 诱导 1 和 2 研究、OCTAVE 维持研究以及 OCTAVE 开放研究的患者（N = 1124；既往未使用 TNFi 治疗失败的患者 N = 541；既往使用 TNFi 治疗失败的患者 N = 583；按既往 TNFi 治疗失败状态分层时，排除 2 期数据）。剂量递增亚组在 OCTAVE 诱导 1 和 2 研究中每日两次服用 10 毫克托法替布，在 OCTAVE 维持研究中每日两次服用 5 毫克托法替布，在 OCTAVE 开放研究中每日两次服用 10 毫克托法替布。
无论既往 TNFi 治疗失败状态如何，托法替布的疗效均优于安慰剂。在 OCTAVE 维持研究和总体队列中，既往使用过 TNFi 治疗失败的托法替布治疗患者中带状疱疹（HZ，包括非严重和严重病例）发生率在数值上高于未使用过 TNFi 治疗失败的患者。对于大多数患者，将剂量递增至每日两次服用 10 毫克托法替布通常可恢复临床反应。剂量递增亚组中的 HZ（非严重和严重病例）发生率在数值上高于总体队列。
无论既往 TNFi 治疗失败状态如何，托法替布对 UC 患者均有效。既往 TNFi 治疗失败的患者中 HZ（非严重和严重病例）发生率在数值上更高。ClinicalTrials.gov：A3921063（NCT00787202）；OCTAVE 诱导 1（NCT01465763）；OCTAVE 诱导 2（NCT01458951）；OCTAVE 维持（NCT01458574）；以及 OCTAVE 开放（NCT01470612）。
