Abstract Background Acute severe active ulcerative colitis (ASUC) often requires rescue therapy when standard medical treatment fails. Data on the use of upadacitinib (UPA) as a rescue option after failure of steroids and infliximab (IFX), and on its long-term outcomes up to 1 year, remain scarce. Methods We retrospectively evaluated hospitalized patients with ASUC (Truelove and Witts criteria) who had failed intravenous steroids and IFX and subsequently received UPA. Outcomes included UPA persistence, clinical remission (CR) (parsiyel MAYO (pMAYO) ≤2), clinical response (≥3 reduction in pMAYO), and colectomy rates over a 1-year follow-up. Results The study included 50 patients, 54% male with median age at UC diagnosis 27 years (Table1a). Most had prior IFX exposure (86%) and over half had received ≥2 biologics. Based on UPA start dates, 92% and 86% of patients were eligible for ITT analyses at weeks 24 and 48, respectively. The overall UPA continuation rate was 52%, with on-treatment continuation of 90% at week 4, 70% at weeks 8 and 16, 60.8% at week 24, and 51.2% at week 48. Discontinuation was due to primary non-response in 41.7%, secondary loss of response in 45.8%, and other causes in 12.5%. UPA-related adverse events occurred in 24% of patients, almost all non-severe; one patient discontinued because of severe leukopenia and herpes zoster. At baseline, all patients had a Mayo endoscopic sub-score of 3 (Table1a). UPA induced rapid improvements in stool frequency, rectal bleeding, pMayo score, and CRP by week 1, maintained up to 48th week in those remaining on treatment (Table1b). The colectomy rate was 22%, with nearly half of surgeries performed within the first week. At week 1, clinical response and CR rates were 60% and 30%, respectively; CR was 46% at week 8 and 42% at week 48 (Figure1a). In ITT analysis to week 48, 23% experienced loss of response, 26% underwent colectomy, and the remainder-maintained CR (Figure1b). Higher baseline CRP, but not disease duration, prior biologics, or steroid/IFX rescue history, was associated with colectomy risk, and no tested factor significantly affected UPA persistence. Conclusion UPA appears to be a promising rescue option in patients with aASUC who fail intravenous steroids and IFX. In this highly refractory cohort, UPA induced rapid clinical and biochemical improvement, with approximately half of patients maintaining CR without colectomy for up to 1 year with an acceptable safety profile. Conflict of interest: Mr. Bakkaloglu, Oguz Kagan: No conflict of interest Unal, Nalan Gulsen: No conflict of interest Akpınar, Atilla: No conflict of interest Eskazan, Tugçe: No conflict of interest Akıncıoğlu, Pırıl: No conflict of interest Kilic, Guner: No conflict of interest Barutcu, Sezgin: No conflict of interest Cavus, Bilger: No conflict of interest Kav, Taylan: No conflict of interest Dincer, Dinc: No conflict of interest Karakan, Tarkan: None Hatemi, Ali Ibrahim: No conflict of interest Erzin, Yusuf Ziya: No conflict of interest Tezel, Hüseyin Ahmet: No conflict of interest Toruner, Murat: No conflict of interest Akyüz, Filiz: No conflict of interest Çelik, Aykut Ferhat: No conflict of interest
Bakkaloglu et al. (Thu,) studied this question.