DOP002 Efficacy and safety of upadacitinib after 4 years of treatment in patients with moderately to severely active ulcerative colitis: interim long-term data from the phase 3 open-label extension study (U-ACTIVATE)

Abstract Background Upadacitinib (UPA), an oral, reversible Janus kinase inhibitor approved for the treatment of ulcerative colitis (UC),1,2 has shown sustained efficacy and an acceptable safety profile in long-term studies of immune-mediated diseases.3,4 Methods We report efficacy and safety of UPA from the U-ACTIVATE (NCT03006068) long-term extension (LTE). Patients (pts) had approximately 4 years (yrs) of maintenance therapy, consisting of 1-yr U-ACHIEVE maintenance and 3 yrs LTE. Pts were randomised to placebo (PBO) or UPA 45 mg once daily (QD) for the 8-week (wk) induction. Clinical responders were re-randomised to PBO, UPA 15 mg QD (UPA15), or UPA 30 mg QD (UPA30) for the 52-wk maintenance. Pts in clinical remission (CR) per Adapted Mayo score (AMS) at wk 52 of the maintenance study continued their double-blind treatment upon entering the LTE. Non-remitters originally randomised to UPA15 were eligible to escalate to UPA30, those randomised to blinded UPA30 continued on blinded UPA30, and those assigned to PBO were eligible to escalate to UPA15 in a blinded manner; see footnote for additional information (Table 1). The study was not designed to compare UPA15 and UPA30 doses. Efficacy was evaluated by CR (per AMS and Partial Mayo score), maintenance of CR per AMS, endoscopic improvement (EI), maintenance of EI, endoscopic remission (ER), and maintenance of ER during the LTE at wk 144. Efficacy data are presented as observed (AO), as well as modified non-responder imputation (mNRI). Treatment-emergent adverse events (TEAEs) were presented as exposure-adjusted event rates (EAERs; events per 100 pt yrs [E/100 PY]); cut-off date: June 30, 2024. Results At LTE wk 144, improvements in CR per AMS and maintenance of CR per AMS were observed in more than half of pts treated with UPA15 or UPA30 (Table 1). ER was achieved by nearly half of pts and more than half of pts maintained ER at LTE wk 144 with UPA15 and UPA30. For safety, 369 pts (UPA15, N=142; UPA30, N=227) with 1043.5 PY (UPA15, 397.4 PY; UPA30, 646.1 PY) of exposure to UPA were analysed (Table 2). Rates of serious TEAEs and TEAEs leading to treatment discontinuation were similar across treatment groups. There was 1 TEAE leading to death (EAER: 0.2 E/100 PY) in a pt requiring prolonged hospitalisation for worsening COVID-19 infection in the UPA30 group. Conclusion Pts achieved and maintained key clinical and endoscopic outcomes through 4 yrs of UPA treatment. Response rates based on mNRI were consistent with the AO approach, supporting the long-term efficacy of UPA. The long-term safety profile for UPA in pts with UC was consistent with previous analyses,1,2 with no new safety risks identified in the ongoing LTE study. These analyses continue to support the favourable benefit–risk in pts with UC. References 1. Danese S, et al. Lancet 2022;399:2113–28 2. Vermeire S, et al. Lancet Gastroenterol Hepatol 2023;8:976–89 3. Fleischmann R, et al. RMD Open 2022;8:e002012 4. Simpson EL, et al. JAMA Dermatol 2022;158:404–13