Real-World Effectiveness and Safety
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Panaccione R.
Parkes G.
Fumery M.
Bettenworth D.
Morisset P.
Mallick M.
Chen S.H.
Suravaram, S.
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2025
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Introduction: Upadacitinib (UPA) is an oral, reversible Janus kinase inhibitor (JAKi) approved for the treatment of patients with moderate-to-severe ulcerative colitis (UC).1-2 Despite substantial evidence from clinical trials supporting the use of UPA for treating UC, real-world (RW) data on its effectiveness and safety remain limited.3 The Prospective Real-World Study of UPA in UC (PROFUNDUS) is an ongoing multi-country, open-label, noninterventional, observational study aimed to evaluate the effectiveness and safety of UPA in patients with moderate-to-severe UC in RW practice (initiated 15 Aug 2022). Aims & Methods: PROFUNDUS recruited 785 adult patients (18 to 75 years [yrs] of age) with moderate-to-severe UC initiating UPA in 16 countries worldwide. UPA was administered in accordance with the terms of the local marketing authorization, with patient treatment determined by the investigator, and patients followed for up to 3 yrs (156 weeks [wk]). This analysis represents data available after the first 500 patients completed 6 months of treatment or discontinued before 6 months, with a data cut-off of 28 Feb 2025. of the first 500 patients who provided informed consent and met the inclusion criteria, the full analysis set (FAS) included 490 patients who initiated a once-daily UPA dosing regimen. This analysis reported baseline demographics and disease characteristics among FAS; the time to achievement of first clinical response per daily Partial Adapted Mayo Score (pAMS) and the percentage of patients achieving clinical response per pAMS at the end of UPA induction (wk 8) or extended induction (wk 16) were reported among evaluable patients who took at least 1 dose of UPA and had available scores to define the outcomes, a subset of FAS. Safety outcomes were analysed through week 26 (6 months), with treatment-emergent adverse events (TEAEs) presented as patient numbers and percentages. Result(s): Among FAS, the patient age range was 18 to 79 yrs; 43.3% were female. At baseline (defined as the last available assessment on or before the first dose date of UPA), pAMS were as follows: 4-5: 18.8%; > 5-6: 6.6%; with score 0 indicative of inactive disease, while a score of 6 indicates active disease and spontaneous bleeding.4 At baseline, 51.3% of patients had a history of intolerance or inadequate response (IR) to advanced therapies (AT-IR), with 13.1% of patients who failed >= 1 JAKi. Among evaluable patients, the median (IQR) time to achieve the first clinical response per daily pAMS was 4 (3.0-8.0) days (N = 373; Table). By the end of induction treatment (wk 8 or 16), 79.6% (258/324) of the evaluable UPA-treated patients achieved clinical response per pAMS (Table). Among UPA-treated patients, the occurrence rates of any treatment-emergent adverse events (TEAEs) and TEAEs possibly related to the study treatment were as follows: any adverse event (AE) (51.2%; 34.9%), serious AEs (5.5%; 2.2%), and severe AEs (5.1%; 2.2%) (Table). Conclusion(s): In this interim analysis of the PROFUNDUS study, UPA demonstrated rapid effectiveness in achieving clinical response in patients with moderate-to-severe UC in RW practice, in a wide variety of age ranges, consistent with the efficacy observed in the UPA UC clinical trials.1 Overall, UPA was well-tolerated, with few serious AEs reported, and most of these were assessed as unrelated to UPA by the investigator.
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United.Eur.Gastroenterol.J.