Background

Tofacitinib is an orally active, small-molecule Janus kinase inhibitor, recently approved for the treatment of moderate to severe ulcerative colitis (UC) refractory to corticosteroid. However, currently, there is inadequate evidence for efficacy of Tofacitinib in UC patients. Therefore, our objective was to evaluate the efficacy and safety of Tofacitinib for inducing and maintaining remission in UC patients.

Methods

In a single-centre retrospective setting, 71 consecutive patients with UC who had failed to respond to corticosteroid or biologics were included. All patients had received 10mg Tofacitinib orally twice daily for at least 8 weeks as remission induction therapy and then, the responders received 5mg twice daily as maintenance therapy for up to 26 weeks. The clinical response and adverse events were evaluated at weeks 8 (induction) and 26 (maintenance). UC activity was assessed by the partial Mayo score. Clinical remission was defined as p-Mayo score ≤1 and the bleeding subscore = 0. Clinical response was defined as p-Mayo score ≤4 and a decrease of ≥3 points relative to baseline. Furthermore, the cumulative remission rates up to 26 weeks were determined by the Kaplan–Meier survival analysis.

Results

At week 8, 24 of 71 patients (33.8%) achieved clinical remission and 20 (28.2%) achieved response level. The mean p-Mayo score fell from 5.8 ± 1.1 at entry to 3.5 ± 2.3 at week 2 (p < 0.01) and 2.3 ± 1.9 at week 8 (P<0.01). The average total cholesterol increased from 180.8 ± 36.0 mg/dl at entry to 206.8±39.3 mg/dl (p < 0.01). In anti-tumour necrosis factor (TNF)-α or vedolizumab (VDZ) naïve subgroup (n = 14), 8 patients (57.1%) achieved response level, while in biologic failure subgroup (n = 57), 36 patients (63.2%) achieved response level. In single biologic failure subgroup (n = 27), 19 patients (70.4%), in double biologics failure subgroup, 14 of 24 patients (58.3%), and in 3 biologics failure subgroup, 3 of 6 patients (50.0%) achieved response level, showing a decrease in the efficacy of Tofacitinib in patients who had failed more than one biologic. Furthermore, of the 25 patients followed for 26 weeks, 23 (92.0%) sustained remission at week 16 and 19 (76.0%) at week 26. Herpes virus infection occurred in 4 patients. The increase in total cholesterol was observed in 68.8% of the patients.

Conclusion

Our retrospective efficacy assessment indicated that Tofacitinib was effective and safe for inducing and maintaining remission in corticosteroid refractory UC patients, regardless of biologic naïve or failure background. The efficacy of 10mg twice daily was rapid and observed within 2 weeks of starting the treatment.

中文翻译：

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P662托法替尼在中度至重度溃疡性结肠炎患者中的疗效和安全性：一项真实世界的回顾性研究

背景

Tofacitinib是一种口服活性小分子Janus激酶抑制剂，最近被批准用于治疗皮质类固醇难治的中度至重度溃疡性结肠炎（UC）。但是，目前，尚无证据表明托法替尼在UC患者中具有疗效。因此，我们的目的是评估Tofacitinib诱导和维持UC患者缓解的疗效和安全性。

方法

在单中心回顾性研究中，纳入了连续71例对皮质类固醇或生物制剂无反应的UC患者。所有患者均接受口服托法替尼10mg口服两次，持续至少8周，作为缓解诱导治疗，然后，应答者每天接受5mg托法替尼作为维持治疗，长达26周。在第8周（诱导）和第26周（维持）评估临床反应和不良事件。通过部分Mayo评分评估UC活动。临床缓解定义为p-Mayo评分≤1，出血评分=0。临床缓解定义为p-Mayo评分≤4，相对于基线降低≥3分。此外，通过Kaplan-Meier生存分析确定了长达26周的累积缓解率。

结果

在第8周，71名患者中有24名（33.8％）达到了临床缓解，20名（28.2％）达到了缓解水平。p-Mayo平均评分从入院时的5.8±1.1降至第2周的3.5±2.3（p <0.01）和第8周的2.3±1.9（P <0.01）。平均总胆固醇从入院时的180.8±36.0 mg / dl增加到206.8±39.3 mg / dl（p <0.01）。抗肿瘤坏死因子（TNF）-α或维多珠单抗（VDZ）初次亚组（n = 14），有8例患者（57.1％）达到了应答水平，而生物衰竭亚组（n = 57），36例（63.2％） ）达到响应水平。在单一生物功能衰竭亚组（n = 27）中，有19名患者（70.4％），在双重生物功能衰竭亚组中，有24名患者中有14名（58.3％），在3个生物制剂衰竭亚组中，有6名患者中有3名（50.0％）获得了缓解水平，证明托法替尼在一种以上的生物制剂治疗失败的患者中疗效下降。此外，在25位随访26周的患者中，有23位（92.0％）在第16周持续缓解，而在26周时有19位（76.0％）持续缓解。4例患者发生了疱疹病毒感染。在68.8％的患者中观察到总胆固醇的增加。

结论

我们的回顾性疗效评估表明，托法替尼在诱导和维持皮质类固醇难治性UC患者的缓解方面是有效且安全的，无论其是否具有生物学天真的或失败的背景。每天两次10mg的疗效迅速，并在开始治疗后2周内观察到。