OP04 Efficacy of upadacitinib in ulcerative colitis: A phase 3 post hoc analysis of biologic- and anti-TNF-inadequate response patients
Vermeire, S.(1)*;Danese, S.(2);Hébuterne, X.(3);D'Haens, G.(4);Takeuchi, K.(5);Finney-Hayward, T.(6);Klaff, J.(6);Holweg, C.T.J.(6);Rubin, D.T.(7);
(1)University Hospital Leuven, Department of Gastroenterology & Hepatology, Leuven, Belgium;(2)Humanitas Clinical and Research Center - IRCCS - and Humanitas University, Department of Biomedical Sciences, Milan, Italy;(3)University Côte d'Azur, Gastroentérology and Clinical Nutrition, Nice, France;(4)Amsterdam University Medical Centers, Department of Gastroenterology and Hepatology, Amsterdam, The Netherlands;(5)Tsujinaka Hospital Kashiwanoha, IBD Center- Department of Gastroenterology and Hepatology, Chiba, Japan;(6)AbbVie Inc, Immunology, North Chicago, United States;(7)University of Chicago Medicine, Section of Gastroenterology- Hepatology and Nutrition, Chicago, United States;
Background
Upadacitinib (UPA), an oral selective and reversible Janus kinase inhibitor, has demonstrated efficacy with a well-characterised safety profile in patients (pts) with moderately to severely active ulcerative colitis (UC) in a Phase 3 clinical trial program.1,2 This post hoc analysis evaluated UPA in pts with an inadequate response (IR; persistently active UC despite ≥1 induction regimen of infliximab, adalimumab, golimumab, vedolizumab or ustekinumab), loss of response, or intolerance to ≥1 biologic (bio-IR) or anti-TNF agent (anti-TNF-IR) in the Phase 3 trials.
Methods
Pts with a clinical response to UPA 45 mg once daily (QD) following 8-week (wk) induction therapy in U-ACHIEVE or U-ACCOMPLISH were subsequently randomised to placebo (PBO), UPA 15 mg or UPA 30 mg QD in U‑ACHIEVE Maintenance.1,2 Here, we evaluated the efficacy of UPA after 8-wk induction and 52-wk maintenance therapy in non-bio-IR pts, bio-IR pts and the subset of anti-TNF-IR pts within the bio-IR population.
Results
Overall, 508 bio-IR pts (51% overall) and 464 anti-TNF-IR pts (91% of bio-IR population) were analysed after induction, and 336 bio-IR pts (49% overall) and 306 anti-TNF-IR pts (91% of bio-IR population) were analysed after maintenance. UPA was significantly more efficacious than PBO across all endpoints analysed at Wk 8 of induction in the non-bio-IR, bio-IR and anti-TNF-IR subgroups (Figure 1; Table 1). At Wk 52 of maintenance, both UPA doses were more efficacious than PBO across subgroups for the primary endpoint of clinical remission per Adapted Mayo score (Figure 2). Adjusted response rate differences for both UPA doses vs PBO were generally similar across most endpoints at Wk 8 of induction and Wk 52 of maintenance for the non-bio-IR, bio-IR and anti-TNF-IR subgroups. At Wk 52 of maintenance, UPA 30 mg QD had numerically better efficacy than 15 mg QD across all endpoints except change from baseline in faecal calprotectin in non-bio-IR patients, with generally similar results for non-bio-IR, bio-IR and anti-TNF-IR pts (Table 2). 
Conclusion
In pts with UC, significantly more pts achieved clinical remission after 8-wk induction and 52-wk maintenance therapy with UPA than PBO in non-bio-IR, bio-IR and anti-TNF‑IR pts. Generally similar efficacy was observed between the bio-IR and anti-TNF-IR pts, which was consistent with the previously published overall population.1,2 These findings suggest that UPA is efficacious for UC regardless of prior therapy with anti-TNF agents or other biologics.