P0898Off-label upadacitinib 60mg daily in the rescue of refractory Ulcerative Colitis: An open labelled cohort study

Abstract Background Although the Janus Kinase Inhibitors (JAKi) upadacitinib (UPA) and tofacitinib are highly efficacious, patients with ulcerative colitis failing UPA, even when dose-escalated to 45mg PO daily, may face colectomy. JAKi have very short half lives and a clear dose-response is evident. Whether dose-escalation to 60mg daily can recapture clinical, biochemical and endoscopic response is unknown. We present a cohort of 10 outpatients with refractory moderate-severe UC that required UPA dose-escalation to 60mg daily. Methods UC patients failing UPA 45mg that escalated to 60mg daily across three tertiary IBD centres in Australia were included. Clinical, biochemical, endoscopic and histologic activity was assessed. Faecal calprotectin (FCP) before and after treatment were compared using the Wilcoxon signed-rank test. Endoscopic remission was defined as Mayo Endoscopic Score 0 and histologic remission defined as Nancy Index 0. Results 10 patients (median age 33 years IQR: 26-42, 80% males, duration of UC 4.8 years IQR: 3.0-15.3, 60% pancolitis, 30% L-sided colitis, 10% pouchitis) with ongoing active UC despite UPA 45mg daily underwent UPA 30mg PO bd dose escalation with a median duration of 3.5 months (IQR:1.4-5.7). All had failed thiopurines and/or at least one other advanced therapy (infliximab: n = 6, vedolizumab: n = 6, adalimumab: n = 1, ustekinumab: n = 2, tulikisobart: n = 1, tofacitinib: n = 1, faecal microbiota transplant: n = 1) and refused surgery. One patient was on UPA 30mg od plus tofacitinib 10mg bd for a total of 180 days. All courses of treatment resulted in symptomatic improvement and 5/11 (45.5%) achieved clinical remission. FCP was significantly improved at week 4 compared to the start of treatment (median 291mg/g IQR: 103-445 vs 93mg/g IQR: 48-441, P=0.006; Figure 1). 7/10 patients had endoscopic assessment after treatment. Of these 5/7 (71.4%) had endoscopic improvement and 2/7 (28.6%) achieved endoscopic remission. 2/7 (28.6%) achieved histologic remission. One patient on infliximab 10mg/kg 4 weekly and UPA 30mg bd developed recurrent CMV colitis. Infliximab was ceased, UPA dropped to 45mg daily and he was successfully treated with ganciclovir. 8/10 (80%) patients were vaccinated with Shingrix prior to treatment and no patients developed shingles. No thromboembolic, cardiovascular, serious infections or IBD flares requiring hospitalisation were seen. Conclusion We report the first case series of UPA 60mg daily demonstrating effectiveness in inducing remission after a median of 3.5 months in patients with refractory UC. UPA 60mg shows promise as a viable option of treatment escalation and appears safe, warranting further investigation into its long-term benefits. Conflict of interest: Dr. Gu, Bonita: Dr Bonita Gu has received sponsorship for conference attendance from Johnson & Johnson and Ferring. Batkhurel, Helen: No conflict of interest Pudipeddi, Aviv: Aviv Pudipeddi has received speaker honoraria or advisory board fees from AbbVie, Dr Falk Pharma, Ferring, Johnson & Johnson, Pfizer and Takeda. Abu-Rgeef, Reeham: No conflict of interest Kariyawasam, Viraj: Educational grants or research support – Ferring, Janssen, AbbVie, Takeda, Shire, WSLHD Research and Education network, Crohn’s and Colitis USA Speaker fees – Janssen, AbbVie, Ferring, Takeda, Pfizer, Shire, Chiesi, Celltrion, GSK, Eli-Lilly, Research Review, Limbic Advisory boards – Janssen, Takeda, Ferring, AbbVie Board director- IBD Sydney organisation (not for profit) Leong, Rupert: advisory board: AbbVie, Aspen, BMS, Celgene, Celltrion, Chiesi, Ferring, Glutagen, Hospira, Janssen, Lilly, MSD, Novartis, Pfizer, Prometheus Biosciences, Takeda, Spyre, Roche research grants: Joanna Tiddy USYD, McCusker Charitable Foundation, Celltrion, Shire, Janssen, Takeda, Gastroenterological Society of Australia, NHMRC, Gutsy Group, Pfizer