Division of Gastroenterology, University of California San Diego, La Jolla, CA, USA.
Pfizer Inc, Collegeville, PA, USA.
Aliment Pharmacol Ther. 2022 Feb;55(4):464-478. doi: 10.1111/apt.16712. Epub 2021 Dec 1.
Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis. We present final data from OCTAVE Open, an open-label, long-term extension study.
The primary objective of OCTAVE Open was to assess the safety and tolerability of long-term tofacitinib in patients with ulcerative colitis; evaluating efficacy was a secondary objective.
Eligible patients included OCTAVE Induction 1&2 non-responders and OCTAVE Sustain completers/treatment failures. Patients in remission at OCTAVE Open baseline received tofacitinib 5 mg b.d.; all others received 10 mg b.d. Incidence rates (unique patients with events/100 patient-years) for adverse events of special interest were calculated; ≤7.0 years of observation. Efficacy endpoints derived from Mayo score were reported ≤36 months (last scheduled endoscopy visit).
In OCTAVE Open, 769 of 944 patients (81.5%) initially received tofacitinib 10 mg b.d. Among all patients (2440.8 patient-years of exposure), incidence rates (IRs; 95% confidence intervals) for deaths and adverse events of special interest were: deaths, 0.25 (0.09-0.54); serious infections, 1.61 (1.14-2.20); herpes zoster (non-serious and serious), 3.16 (2.47-3.97); opportunistic infections, 0.87 (0.54-1.33); major adverse cardiovascular events, 0.16 (0.04-0.42); malignancies (excluding non-melanoma skin cancer), 1.03 (0.67-1.52); non-melanoma skin cancer, 0.75 (0.45-1.19); deep vein thrombosis, 0.04 (0.00-0.23); pulmonary embolism, 0.21 (0.07-0.48). At Month 36, 66.9% and 40.3% showed clinical response, 64.6% and 37.1% had endoscopic improvement, and 58.9% and 33.7% maintained or achieved remission, with tofacitinib 5 and 10 mg b.d. respectively.
Tofacitinib demonstrated consistent safety up to 7.0 years. Data collected up to Month 36 support long-term efficacy beyond the 52-week maintenance study.
托法替布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。我们报告了 OCTAVE Open 的最终数据，这是一项开放标签、长期扩展研究。
OCTAVE Open 的主要目的是评估溃疡性结肠炎患者长期接受托法替布治疗的安全性和耐受性；评估疗效是次要目标。
合格的患者包括 OCTAVE 诱导 1&2 无应答者和 OCTAVE 维持完成者/治疗失败者。在 OCTAVE Open 基线时处于缓解期的患者接受托法替布 5mg，每日两次；其余患者接受托法替布 10mg，每日两次。计算不良事件特别关注的发生率（每 100 患者年发生不良事件的独特患者数）；观察时间≤7.0 年。从 Mayo 评分得出的疗效终点报告≤36 个月（最后一次计划内镜检查访问）。
在 OCTAVE Open 中，944 名患者中的 769 名（81.5%）最初接受托法替布 10mg，每日两次。在所有患者（2440.8 患者年暴露）中，死亡率和不良事件特别关注的发生率（IRs；95%置信区间）为：死亡，0.25（0.09-0.54）；严重感染，1.61（1.14-2.20）；带状疱疹（非严重和严重），3.16（2.47-3.97）；机会性感染，0.87（0.54-1.33）；主要不良心血管事件，0.16（0.04-0.42）；恶性肿瘤（不包括非黑色素瘤皮肤癌），1.03（0.67-1.52）；非黑色素瘤皮肤癌，0.75（0.45-1.19）；深静脉血栓形成，0.04（0.00-0.23）；肺栓塞，0.21（0.07-0.48）。在第 36 个月时，66.9%和 40.3%患者显示临床缓解，64.6%和 37.1%患者内镜改善，58.9%和 33.7%患者维持或达到缓解，分别接受托法替布 5mg 和 10mg，每日两次。
托法替布的安全性一致，最长可达 7.0 年。截至第 36 个月收集的数据支持长期疗效超过 52 周的维持研究。
