S1984 Efficacy of Retreatment With Upadacitinib After Treatment Interruption in Ulcerative Colitis: Data From the U-ACTIVATE Open-Label Extension

Introduction: Upadacitinib (UPA) is an oral, reversible Janus kinase inhibitor (JAKi) approved for the treatment of moderate-to-severe ulcerative colitis (UC). In clinical practice, patients may temporarily discontinue JAKis and then restart treatment for varying reasons; however, the efficacy of UPA in this scenario has not been fully characterized. Here, we assess the efficacy of UPA in patients with UC who lost response when UPA treatment was interrupted and then retreated with the lowest dose through 144 weeks (wks). Methods: This analysis of the U-ACTIVATE (NCT04988386) open-label extension (OLE) included the subset of patients in the U-ACHIEVE or U-ACCOMPLISH studies who responded to 8 wks of UPA 45 mg once daily (QD) induction therapy and were then re-randomized to placebo (PBO) for maintenance. Patients who subsequently lost response on PBO entered the OLE and were treated with UPA 15 mg QD (UPA15); those who had inadequate response on UPA15 were then escalated to UPA30. Clinical remission per adapted Mayo score and partial adapted Mayo score, endoscopic improvement, and endoscopic remission were assessed at wks 48, 96, and 144. Safety was not assessed in this analysis but has been reported previously.1 Results: A total of 110 patients who lost response after UPA 45 mg induction and withdrawal to placebo entered the U-ACTIVATE OLE and were treated with UPA15; at wk144, 57 remained on UPA15 (UPA15-UPA15), 47 were escalated to UPA30 (UPA15-UPA30), and 6 were de-escalated to UPA15 after the escalation and thus were not included in this analysis. Clinical remission per adapted Mayo score was achieved by 52.4%, 66.7%, and 76.3% of patients at wks 48, 96, and 144, respectively, in the UPA15-UPA15 group and 48.3%, 59.4%, and 61.1% of patients in the UPA15-UPA30 group. Most patients in both UPA treatment groups achieved clinical remission per partial adapted Mayo score all time points. Similar results were observed for endoscopic improvement. Endoscopic remission was achieved by 31.3%, 40.0%, and 33.3% of patients at wks 48, 96, and 144, respectively for UPA15-UPA15 and 30.0%, 56.3%, and 56.4% of patients for UPA15-UPA30. Conclusion: In most patients with UC who lost response following temporary UPA treatment interruption, clinical and endoscopic efficacy were recaptured following treatment with UPA15 and/or escalation to UPA30 in case of inadequate response in the U-ACTIVATE OLE. Reference Panaccione et al. J Crohns Colitis. 2024;18[Suppl 1]:i1821–2.