P0577real world durability of response and remission with upadacitinib in Ulcerative Colitis: a multi-centre study

Abstract Background We aimed to describe the real-world durability of clinical and endoscopic outcomes of upadacitinib (UPA) in ulcerative colitis (UC). Methods We retrospectively analyzed an ongoing multi-center cohort of UC patients(pts) in the United States who were started on UPA for active disease. Primary outcome was clinical remission at 1yr assessed by partial Mayo score(pMS)(resolution of all UC related symptoms and physician global assessment). Secondary outcomes assessed at various timepoints, including after re-escalation, included clinical response(50%reduction in symptoms utilizing the pMS), endoscopic response (Mayo endoscopic score≤1or absence of erosions/ulcerations) and histological remission(defined as normal or chronic inactive). Durable secondary outcomes achieved at both 6months and at 1yr and beyond were also assessed. Descriptive statistics were performed. Adverse events(AEs) investigated included cardiovascular events and herpes zoster (HZ). Results 416pts were included(Table 1) with median values for age at initiation of36.00yrs(range27-48), disease duration7.00yrs(range3-14)and follow-up 993days(IQR,672-1103), with206(49.52%)with follow-up at 1yr or beyond. Of these, 66.1%had extensive colitis. Induction duration was8wks in 86.5%and16wks in 4.8 %(20/416). Most received an induction dose of45mg(97.1%)and maintenance dose of30mg(85.8%). Among the evaluable population at1yr and beyond, 62.5%(45/80)were in clinical remission, 75.9%(22/29)in endoscopic response with58.6%(17/29) in remission and66.6%(20/30)in histological remission. At 6months, clinical remission was51.6%(42/93), endoscopic response was 75%(24/32) of which43.75%(14/32)were in remission and histologic remission was seen in 40.8%(20/49).Durable secondary outcomes of clinical remission were seen in 71.4%(30/42), endoscopic improvement in 45.8%(11/24), and histologic remission in35%(7/20). Re-escalation to 45mg occurred in 35pts, of which48.6%(17/35)were re-escalated due to incomplete induction clinical response with all achieving response(11 in remission). The rest(18/35)were re-escalated for clinical relapse after initial remission where72.2%(13/18)were able to recapture remission. After re-escalation,54.3%(19/35)continued on 45mg daily. AEs were reported in12.7%with HZ in 7pts(2.1%). One pt aged53yrs had an episode of TIA after 1yr on UPA at 15mg, without pre-existing cardiovascular risk factors and UPA use is ongoing at the same dose. There were no reported episodes of worsening of pre-existing cardiovascular disease or DVT/PE. Conclusion UPA is durably effective and safe in a real-world clinical setting with re-escalation to 45mg capturing response in a majority of the pts. Ongoing recruitment will provide further evidence on long term effectiveness and safety. Conflict of interest: Ms. Huang, Katherine: No conflict of interest Chandnani, Arun: No conflict of interest Samaan, Sami: None Tan, Tingyi: I have no conflict of interests to declare. Ramesh, Prajith Raj: None Conlon, Caroline: No conflict of interest Klein, Jeremy: None Reddy, Nikhil: No conflict of interest Ayoub, Malek: None Cervantes Limon, Gabriela: none Myers, Melissa: None Bucaram, Martha: No conflict of interest Lieto, Stephen: No conflict of interest Scalzo, Nicholas: No conflict of interest Cohen, Benjamin: Abbvie - consulting and speaking ALPCO - consulting J & J Innovative Medicine - consulting Takeda - consulting and speaking Emmes Biopharma Services LLC - DSMB Pfizer - consulting Mohamed, Islam: nothing to declare Ciorba, Matthew: Advisory Board: Janssen, AbbVie, Pfizer, Geneoscopy Consulting: Janssen, AbbVie, Pfizer, Geneoscopy Grant contracts: Janssen, Pfizer, Incyte Shukla, Richa: Speakers bureau - Abbvie and Lilly Wright, Michael: None Xu, An Tao: No conflict of interest Chowla, Navreet: No conflict of interest Ogholikhan, Sina: Abbvie Medical Director Kujawski, Michelle: Abbvie Scientific Director Dulaney, David: Speaker bureau - Regeneron Speaker bureau - Sanofi Speaker bureau - Takeda Speaker bureau - Eli Lilly Fenster, Marc: none Benson, Caroline: No conflict of interest Alhobayb, Tamara: No conflict of interest Berinstein, Jeffrey: No conflict of interest Shivashankar, Raina: Abbvie and BMS - speaker bureau Janssen and Celltrion - grant for IBD fellowship funding Pfizer - consultant Bishu, Shrinivas: None Patel, Anish: speaker: abbvie, J & J, Lilly, BMS, Pfizer, Phathom, Takeda consultant: abbvie Ungaro, Ryan: Personal Fees: AbbVie, Bristol Myers Squibb, Genentech, Lilly, Pfizer, Janssen, Takeda Johnson, Amanda: Research grant: Abbvie, Spyre Therapeutics Pekow, Joel R.: CVS Health - Consulting Abbvie, Eli Lilly, Pfizer, Johnson and Johnson - Stocks Yarur, Andres: Personal Fees: Consultant for Takeda, Pfizer, Roche, Merck, Abbvie, Eli Lilly. Bristol Myers Squibb, Celltrion, Johnson and Johnson. Deepak, Parakkal: Parakkal Deepak has received research support under a sponsored research agreement unrelated to the data in the abstract from AbbVie, Johnson and Johnson, Sanofi, Merck, Teva, Direct Biologics, Tr1x, Boehringer Ingelheim, Bristol Myers Squibb, Pfizer, Prometheus Biosciences, Takeda Pharmaceuticals, Roche Genentech, Eli Lilly, AstraZeneca, Spyre and Agomab, has received consulting fees from Johnson and Johnson, Abbvie, Merck, Sobi, Celltrion, Fresenius Kabi, Asahi Kasei Pharma, Sandoz and CorEvitas, LLC and has served on the board of the Srategic Alliance for Intercultural Advocacy in GI.