P0691High rates of response to treatment with upadacitinib in patients with ulcerative colitis and prior exposure to tofacitinib

Abstract Background Tofacitinib (TOFA) and Upadacitinib (UPA) are inhibitors of Janus Kinases (JAKi) with different target specificities, as TOFA inhibits JAK1 and JAK3, while UPA primarily targets JAK1. Aim of the present study was to record the efficacy of UPA in patients with active ulcerative colitis (UC), who had previously been treated with TOFA. Methods This prospective cohort study included patients with active moderate-to-severe UC, who initiated UPA after 1/1/2024 and who had previously been treated with TOFA. Each patient was treated with 45mg daily for the 8-week induction period, followed by 45, 30 or 15mg as maintenance dose. Our primary end-point was clinical remission (Clin-Rem) PRO-Rectal bleeding = 0 and PRO-bowel movement = 0 at week 24. Secondary end-points were clinical response (Clin-Resp) drop of at least 50% of the baseline PROs, Clin-Rem and corticosteroid-free clinical remission (Cs-F-Rem) at week 8, Clin-Resp, Cs-F-Rem, endoscopic improvement and mucosal healing endoscopic MAYO = 0 at week 24, maintenance dose of UPA and adverse events on treatment. Data were analyzed using SPSSv23. Results We have included 32 patients 23 male, mean age:39.4 years (SD = 13.7), median disease duration:5.9 years (IQR:4.1-10.3). The majority of the patients (59.4%) were exposed to ≥ 3 advanced treatments and 8 (25%) to ≥ 4. TOFA was discontinued in 15 (46.9%) patients due to primary non-response and in 17 (53.1%) due to secondary loss of response with a median treatment duration of 10 months (IQR:4.3-18.4). At week 8, 24 (75%) patients achieved Clin-Resp and 11 (34.4%) Clin-Rem. Twenty-three patients commenced maintenance treatment with 30mg daily, one with 15mg and 6 patients required extended induction with 45mg daily. At week 24 Clin-Rem was achieved by 13 (40.6%) patients. Detailed rates for the secondary end-points are presented in the Figure. Clin-Rem at week 24 significantly correlated with older age (OR = 1.06, 95%CI:1.00-1.13) and showed a tendency for association with E3 Montreal classification (OR = 0.22, 95%CI:0.05-1.06), PRO-”bowel movement” (OR = 0.40, 95%CI:0.15-1.07) and baseline endoscopic MAYO score (OR = 0.26, 95%CI:0.07-1.00). Clin-Resp at week 4 (11/18 vs 0/11, P = 0.001), as well as Clin-Resp (13/24 vs 0/8, P = 0.007) and Clin-Rem (9/11 vs 4/21, P = 0.001) at week 8 were predictive of Clin-Rem at week 24. Adverse events occurred in 10 (31.3%) patients with hyperlipidemia being the most prevalent in 7 patients. Conclusion In this cohort of refractory patients who were exposed to tofacitinib, Upadacitinib showed remarkably good response rates. Younger age and higher disease burden at initiation decrease the probability of clinical remission, while early clinical response and remission appear to predict persistence of clinical remission. Conflict of interest: Dr. Kokkotis, Georgios: No conflict of interest Kitsou, Vasiliki: No conflict of interest Ioannou, Alexandros: No conflict of interest Striki, Athanasia: No conflict of interest Lakiotaki, Dimitra: No conflict of interest Mousourakis, Konstantinos: No conflict of interest Kyriakos, Nikolaos: No conflict of interest Fousekis, Fotios: No conflict of interest Athanasiadou, Eftychia: No conflict of interest Vlachou, Evangelina: No conflict of interest Viazis, Nikolaos: No conflict of interest Zampeli, Evanthia: I have received honor-aria and speaker fees from Abbvie, Janssen, Pfizer,Takeda, MSD, AMGEN, Genesis, Ferring, Mylan, BMS, Galenica Liatsos, Christos: No conflict of interest Michalopoulos, George: speaker fees TAKEDA, ABBVIE, MSD, GALENICA, ENORASIS, AMGEM PFEIZER Karatzas, Pantelis: No conflict of interest Karmiris, Konstantinos: Personal Fees: Speaker fees from Abbvie, BMS, Eli-Lilly, Genesis, Innovis, Johnson & Johnson, Pfizer and consultancy or advisory board member fees from Abbvie, BMS, Faran, Ferring, Genesis, Johnson & Johnson, Pfizer, Roche and Takeda Theodoropoulou, Angeliki: No conflict of interest Soufleris, Konstantinos: No conflict of interest Koutroubakis, Ioannis E.: No conflict of interest Tzouvala, Maria: No conflict of interest Katsanos, Konstantinos: AbbVie, Amgen, Athos, Αenorasis, Biocon,Biogaia, Drugssales Ltd, Epsilon Health, Falk, Faran, Ferring, Genesis, Grifols S.A., Hospital line, Johnson & Johnson, COPER, MSD, Biocon, Pfizer, Potamitis Medicare, Rafarm, Petsiavas, Shire,Takeda, Vianex, Lilly Giouleme, Olga: No conflict of interest Bamias, Giorgos: Grants: Grants from Takeda, AbbVie, Mylan/Viatris/Biocon, Genesis Pharma, Ferring, Vianex, and Aenorasis Consulting Fees and Speaker Honoraria: AbbVie, Adacyte Therapeutics, Amgen, Bristol Myers Squibb, Faran, Ferring, Galenica, Genesis Pharma, J & J, Lilly, MSD, Mylan/Viatris/Biocon, Pfizer, Shattuck Labs, Takeda, Vianex