Background

Tofacitinib (TFC) is an oral, small-molecule Janus kinase inhibitor, which was recently approved for moderate to severe ulcerative colitis (UC). The aim of the current real-life study was to determine efficacy of TFC induction therapy regarding the clinical response and remission in patients with active UC. We evaluated short-term efficacy data in a Hungarian cohort with prior exposure to other biological agents such as anti-TNF drugs and vedolizumab.

Methods

In this single-centre retrospective study, patients with TFC introduction were included. Since January 2019, a total of 16 patients received an oral TFC induction therapy in a dose of 10 mg twice daily for 8 weeks. Endoscopic activity was evaluated by endoscopic Mayo (eMayo) score before the introduction of TFC and in case of an inadequate therapeutic response to the 5-mg-therapy to confirm therapeutic decision-making. Based on the evaluation of clinical symptoms and laboratory parameters, we either kept the dosage or reduced the dose to 5 mg according to local regulations. We also collected data from the 16. and 24. weeks of the therapy. Primary endpoints were a clinical response (as a reduction in partial Mayo Score [pMayo] by minimum 3 points) or remission (as a Mayo score of the maximum of 2 points and without blood in stool) at week 8.

Results

Sixteen patients had received the induction therapy (mean age: 36 years, 7 males and 9 females) in our centre. After 8 weeks, 12 (75%) patients responded to the TFC induction therapy and 6 (37.5%) of them were in remission. Four patients were primary non-responders (25%). Corticosteroid therapy (18 ± 7 mg) was required during the induction in 4 responder cases, which could be stepped down by week 8. As a continuous maintenance therapy, 4 patients have already reached the 16th week and 8 have completed the 24th week. By the end of the follow-up, 12 patients responded and 10 was in remission. During the observation period, 3 patients had to remain on 10 mg TFC dose, 6 patients required dose escalation from 5 mg to 10 mg and 5 mg was sufficient in case of only 3 patients after the introduction. Endoscopic activity showed a moderate decrease from 2.5 ± 0.5 eMayo score to 2 ± 1 (n = 7) until week 16. In respect the responder patients, CRP levels decreased from the mean of 7.23 to 5.02. No serious side-effects were observed during the follow-up.

Conclusion

After the 8-week TFC induction therapy, the response rate was high and only every fourth patients were non-responder. A low number of patients had adequate reactions to the 5 mg-therapy after the introduction, but TFC is effective with dose-escalation in respect of clinical response and remission in patients with UC, who have had an inadequate response to previous biological therapy.

中文翻译：

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P663托法替尼在先前无效的生物疗法后对溃疡性结肠炎患者的疗效

背景

Tofacitinib（TFC）是一种口服小分子Janus激酶抑制剂，最近被批准用于中度至重度溃疡性结肠炎（UC）。当前的现实生活研究的目的是确定TFC诱导疗法对活动性UC患者的临床反应和缓解的疗效。我们在匈牙利人群中评估了短期功效数据，并事先接触了其他生物制剂，例如抗TNF药物和vedolizumab。

方法

在这项单中心回顾性研究中，纳入了TFC引入患者。自2019年1月以来，共有16位患者接受了口服TFC诱导治疗，剂量为10 mg，每天两次，共8周。在引入TFC之前以及在对5毫克疗法的治疗反应不足以确认治疗决策的情况下，通过内窥镜Mayo（eMayo）评分评估内窥镜活动。根据临床症状和实验室参数的评估，我们要么保持剂量不变，要么根据当地法规将剂量降低至5 mg。我们还从治疗的16周和24周收集了数据。主要终点为第8周时的临床反应（部分Mayo评分[pMayo]降低至少3分）或缓解（以Mayo评分的最高2分且无便血）。

结果

我们中心有16名患者接受了诱导治疗（平均年龄：36岁，男7例，女9例）。8周后，有12名（75％）患者对TFC诱导疗法有反应，其中6名（37.5％）处于缓解状态。四名患者是原发性无反应者（25％）。在4例应答者中，诱导期间需要使用皮质类固醇激素疗法（18±7 mg），可以在第8周前下调治疗。作为持续维持疗法，有4例患者已经达到第16周，而8例已经完成了第24周。随访结束时，有12例患者缓解，10例患者缓解。在观察期内，3例患者必须继续服用10 mg TFC剂量，6例患者需要将剂量从5 mg逐步提高到10 mg，并且在引入后仅3例情况下5 mg就足够了。内窥镜活动从2开始适度下降。eMayo评分从5±0.5降低到2±1（n = 7），直到第16周。对于有反应的患者，CRP水平从平均值7.23降至5.02。随访期间未观察到严重的副作用。

结论

经过8周的TFC诱导治疗后，缓解率很高，只有四分之一的患者无反应。引入后，少数患者对5 mg疗法有足够的反应，但对于先前对生物疗法反应不足的UC患者，TFC在临床反应和缓解方面可提高剂量。