Real-world effectiveness, symptomatic improvement, and safety of upadacitinib in patients with moderate-To-severe ulcerative colitis: Interim findings from the profundus study

Abstract

Background: Upadacitinib (UPA), an oral Janus kinase inhibitor (JAKi), is approved for the treatment of moderate-To-severe ulcerative colitis (UC).1,2 The Prospective Real-World Study of UPA in UC (PROFUNDUS) is an open-label, noninterventional study evaluating physician prescribing patterns and clinical endpoints among UPA-Treated patients with moderate-To-severe UC in routine clinical practice (initiated 15Aug2022); this interim analysis assesses real-world (RW) clinical effectiveness, symptomatic improvement, and safety.4 Methods: Patients, comprising 494 of the first 500 eligible adults (18-79 years yrs]), in the full analysis set (FAS), with moderate-To-severe UC who initiated once-daily UPA across 16 countries, per investigator discretion and according to the local label; steroid tapering was not mandated and left to investigator discretion. Baseline (BL) demographics and disease characteristics were reported among FAS; endpoints assessed included clinical response per Partial Adapted Mayo score (PAMS), corticosteroid (CS)-free response per PAMS, clinical remission (CR) per Partial Mayo score, absence of abdominal pain, and absence of bowel urgency at week 26 among evaluable FAS pts and by advanced therapy (AT) status (AT-experienced vs AT-naive; cut-off date: 28Feb2025). Safety endpoints were assessed, with treatment-emergent adverse events (TEAEs) reported as counts and percentages. Result(s): Among FAS at BL (last measurement on or before the initial UPA dose), the mean (SD) patient age was 39.4 (13.3) yrs, with 57.1% males, 21.5% on CS; mean (SD) disease duration was 7.8 (7.0) yrs, with 54.6% of patients being AT-experienced, 41.9% failed >=1 TNF, and 14.2% failed >=1 JAKi. At week 26, 81.8%, 72.4%, 66.3%, and 71.9% of patients achieved clinical response, CR, no abdominal pain, and no bowel urgency, respectively; among those on BL CS, 64.4% attained CS-free response (Table 1). Similar results were observed for all endpoints regardless of AT status (Table 1). Among patients treated with UPA45/UPA15, UPA45/UPA30, or any UPA dose, TEAEs were as follows: Any AE, 66.0%; 50.8%; 51.4%, serious AEs, 3.8%; 4.6%; 5.7%, and severe AEs, 5.7%; 4.0%; 5.5% (Table 2). Within this overall cohort, the subgroup of patients who experienced TEAEs potentially related to UPA exhibited serious and severe AEs at 3.6%, 6.3%, 6.9%, and 7.1%, 5.4%, 6.9%, respectively (Table 2). Conclusion(s): In the PROFUNDUS study, UPA-Treated patients with UC achieved high rates of clinical and symptomatic improvement, regardless of AT status within an RW setting. Overall, UPA was well-Tolerated, with few serious AEs observed, most of which were unrelated to UPA, as determined by the study investigator.