Background

Tofacitinib is an oral, small-molecule JAK inhibitor for the treatment of ulcerative colitis (UC). Efficacy and safety of tofacitinib were demonstrated in patients with moderate to severe UC in 3 Phase 3 studies.¹ Here, we present data from an ongoing, open-label, long-term extension (OLE) study.²

Methods

We present updated safety and efficacy data from the OLE study (OCTAVE Open, NCT01470612; as of May 2019, database not locked). Eligible patients included non-responders (Week 8 data) in OCTAVE Induction 1 and 2 (NCT01465763; NCT01458951) and completers (Week 52 data) or treatment failures (early-termination data) in OCTAVE Sustain (NCT01458574). Patients in remission (total Mayo score ≤2, no individual subscore >1, rectal bleeding [RB] subscore 0) at Week 52 of OCTAVE Sustain (central read) received tofacitinib 5 mg twice daily (BID); all others received 10 mg BID. Induction non-responders without clinical response (≥3-point and ≥30% decrease from induction study baseline total Mayo score, plus ≥1-point RB subscore decrease or absolute RB subscore ≤1) at Month 2 of the OLE study were withdrawn. Incidence rates (IRs) for adverse events (AEs) of special interest were calculated (no. of unique patients with events per 100 patient-years). Efficacy endpoints were derived from Mayo score (local read) with non-responder and last observation carried forward imputation (NRI-LOCF) [a].

Results

Of 944 patients who received ≥1 dose of tofacitinib, 769 (81.5%) received 10 mg BID (median duration [range]: 5 mg BID 1170 [36–2066]; 10 mg BID 668 [1–2159] days). In total, 338 (35.8%) and 93 (9.9%) patients discontinued due to insufficient clinical response and AEs (excl. worsening UC), respectively. IRs (95% confidence interval) in the Tofacitinib. All group were: deaths 0.18 (0.05, 0.47); serious infections 1.57 (1.08, 2.19); herpes zoster (non-serious and serious) 3.27 (2.54, 4.14); major adverse cardiovascular events 0.14 (0.03, 0.40); malignancies excl. non-melanoma skin cancer (NMSC) 0.92 (0.56, 1.42); NMSC 0.74 (0.43, 1.21); deep vein thrombosis 0.05 (0.00, 0.25); pulmonary embolism 0.18 (0.05, 0.47) (Table). At Month 36 (NRI-LOCF), 58.9% (n = 103) and 33.5% (n = 257) were in remission, 64.6% (n = 113) and 37.0% (n = 284) had mucosal healing (Mayo endoscopic subscore of 0 or 1) [b] and 66.9% (n = 117) and 40.2% (n = 309) showed clinical response, in the 5 and 10 mg BID groups, respectively.

Conclusion

Incidence of AEs remained generally consistent in patients with moderate to severe UC in the OLE study compared with a previous analysis.² Data continue to support long-term efficacy with tofacitinib up to 36 months beyond Week 52 of OCTAVE Sustain.

References

• Sandborn WJ et al. N Engl J Med 2017;376:1723–36
• Lichtenstein GR et al. United Eur Gastroenterol J 2019;7:Abstract OP213

中文翻译：

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DOP61 Tofacitinib，一种口服小分子Janus激酶抑制剂，用于治疗溃疡性结肠炎：一项长达5.9年的开放性长期研究的分析

背景

Tofacitinib是一种口服小分子JAK抑制剂，用于治疗溃疡性结肠炎（UC）。在3个3期临床研究中，tofacitinib在中度至重度UC患者中的疗效和安全性得到了证实。¹在这里，我们提供了正在进行的，开放标签的长期扩展（OLE）研究的数据。²

方法

我们提供了OLE研究的最新安全性和功效数据（OCTAVE Open，NCT01470612;截至2019年5月，数据库未锁定）。符合条件的患者包括OCTAVE Induction 1和2（NCT01465763; NCT01458951）中的无反应者（第8周数据）和OCTAVE Sustain（NCT01458574）中的完成者（第52周数据）或治疗失败（早期终止数据）。在OCTAVE维持期第52周（中央阅读）缓解的患者（总Mayo得分≤2，无单个子评分> 1，直肠出血[RB]子评分0），接受托法替尼5 mg每天两次（BID）；所有其他人均接受10 mg BID。在OLE研究的第2个月中，无临床反应的诱导无反应者（比诱导研究基线总Mayo得分降低≥3分，≥30％，再加上≥1分RB子评分降低或绝对RB子评分≤1）被撤回。计算出特殊关注的不良事件（AE）的发生率（IR）（每100个病人年中发生事件的唯一患者数）。功效终点来自无反应者的Mayo评分（本地阅读），最后观察到的是结转归因（NRI-LOCF）[a]。

结果

在接受≥1剂量托法替尼的944例患者中，有769（81.5％）接受了10 mg BID（中位持续时间[范围]：5 mg BID 1170 [36-2066]； 10 mg BID 668 [1-2-2159]天）。总共有338例（35.8％）和93例（9.9％）的患者因临床反应不足和AEs（不包括UC恶化）停药。Tofacitinib中的IR（置信区间为95％）。所有组均为：死亡0.18（0.05，0.47）；严重感染1.57（1.08，2.19）; 带状疱疹（严重且不严重）3.27（2.54，4.14）; 主要不良心血管事件0.14（0.03，0.40）; 恶性肿瘤除外 非黑色素瘤皮肤癌（NMSC）0.92（0.56，1.42）; NMSC 0.74（0.43，1.21）；深静脉血栓形成0.05（0.00，0.25）; 肺栓塞0.18（0.05，0.47）（表）。在第36个月（NRI-LOCF），缓解率分别为58.9％（n = 103）和33.5％（n = 257），64.6％（n = 113）和37。

结论

与先前的分析相比，OLE研究中中度至重度UC患者的AE发生率总体保持一致。²在OCTAVE Sustain的第52周之后的36个月内，数据继续支持托法替尼的长期疗效。

参考文献

• Sandborn WJ等。N Engl J Med 2017； 376：1723–36
• Lichtenstein GR等。United Eur Gastroenterol J 2019; 7：Abstract OP213