Efficacy of Upadacitinib Retreatment or Dose Escalation After Loss of Response in Ulcerative Colitis: Data From the Open-Label Extension of the U-ACTIVATE Study

IF 3.3

Gastro hep advances Pub Date : 2026-01-01 Epub Date: 2026-04-13 DOI:10.1016/j.gastha.2026.100969

Remo Panaccione , Jean-Frédéric Colombel , Marla Dubinsky , Christopher Ma , Michelle Kujawski , Erica Cheng , Elena Dubcenco , Sina Ogholikhan , Elena Marced Barrachina , Tadakazu Hisamatsu

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Abstract

Background and Aims

Upadacitinib (UPA) is a Janus kinase inhibitor approved for moderately to severely active ulcerative colitis (UC). Patients may discontinue and then restart UPA treatment or require dose adjustment; however, the impact on overall efficacy of treatment interruption or dose escalation is not fully characterized. This analysis of the U-ACTIVATE (NCT03006068) open-label extension (OLE) study evaluated the efficacy of UPA retreatment after UPA withdrawal or dose escalation during UPA maintenance following a loss of response in patients with UC.

Methods

Patients who responded to 8 weeks of UPA 45 mg induction therapy were rerandomized to placebo, UPA 15 mg (UPA15), or 30 mg (UPA30) in the 52-week U-ACHIEVE (NCT02819635) maintenance study. Patients who subsequently lost response on placebo during maintenance could enter the U-ACTIVATE OLE and were retreated with UPA at a 15 mg dose (UPA retreatment group); patients who lost response on maintenance UPA15 continued UPA15 during the OLE. Patients who lost response on UPA15 during the OLE and met prespecified criteria were escalated to UPA30. Clinical and endoscopic remissions were assessed through week 144. Safety was not assessed in this analysis but has been reported previously.

Results

The UPA retreatment group enrolled 110 patients; 57 remained on UPA15 (UPA15OLE→UPA15) and 47 were escalated to UPA30 (UPA15OLE→UPA30) by week 144. A total of 39 patients lost response on maintenance UPA15 and entered the OLE on UPA30 (UPA15Maint→UPA30). At week 144, the following proportion of patients achieved clinical remission per adapted Mayo score and endoscopic remission, respectively: UPA15OLE→UPA15: 76.3% and 33.3%, UPA15OLE→UPA30: 61.1% and 56.4%, and UPA15Maint→UPA30: 43.5% and 40.7%.

Conclusion

In patients with UC, clinical and endoscopic efficacy could be recaptured following UPA retreatment or dose escalation in the U-ACTIVATE OLE.

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溃疡性结肠炎患者疗效丧失后，Upadacitinib再治疗或剂量递增的疗效：来自U-ACTIVATE研究开放标签扩展的数据

背景和目的supadacitinib （UPA）是一种Janus激酶抑制剂，被批准用于治疗中度至重度活动性溃疡性结肠炎（UC）。患者可能会停止然后重新开始UPA治疗或需要调整剂量；然而，治疗中断或剂量增加对总体疗效的影响尚未完全确定。这项U-ACTIVATE （NCT03006068）开放标签扩展（OLE）研究的分析评估了UC患者在停用UPA后再治疗UPA或在疗效丧失后维持UPA期间增加剂量的疗效。方法在为期52周的U-ACHIEVE （NCT02819635）维持研究中，对8周UPA 45 mg诱导治疗有反应的患者被重新随机分为安慰剂、UPA15 mg （UPA15）或30 mg （UPA30）。随后在维持期间安慰剂失去反应的患者可以进入U-ACTIVATE OLE，并以15mg剂量的UPA （UPA再治疗组）进行治疗；维持UPA15无效的患者在OLE期间继续使用UPA15。在OLE期间UPA15无效且符合预定标准的患者升级至UPA30。通过第144周评估临床和内镜缓解情况。该分析未对安全性进行评估，但此前已有报道。结果UPA再治疗组入组110例；到第144周，57名患者继续使用UPA15 (UPA15OLE→UPA15)， 47名患者升级为UPA30 （UPA15OLE→UPA30）。39例患者维持UPA15无效，UPA30进入OLE （UPA15Maint→UPA30）。在第144周，根据Mayo评分和内镜下缓解，达到临床缓解的患者比例分别为：UPA15OLE→UPA15: 76.3%和33.3%,UPA15OLE→UPA30: 61.1%和56.4%,UPA15Maint→UPA30: 43.5%和40.7%。结论在UC患者中，在UPA再治疗或U-ACTIVATE OLE剂量增加后，临床和内镜疗效可以恢复。

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