DOP42 Efficacy and safety of deucravacitinib, an oral, selective tyrosine kinase 2 inhibitor, in patients with moderately-to-severely active Ulcerative Colitis: 12-week results from the Phase 2 LATTICE-UC study

Abstract Background Tyrosine kinase 2 (TYK2) is an intracellular that mediates the signalling of key cytokines involved in ulcerative colitis (UC) pathophysiology. Deucravacitinib (DEUC) a novel, oral, selective TYK2 inhibitor binds to regulatory domain. The safety and efficacy DEUC were evaluated patients (pts) with moderately-to-severely active UC. Methods LATTICE-UC (NCT03934216), randomised, double-blind, placebo (PBO)-controlled, multicentre, Phase trial, enrolled pts UC (modified Mayo score 5 9 [endoscopic {ES} subscore ≥2, rectal bleeding {RB} ≥1, stool frequency {SF} ≥2) inadequate response, loss or intolerance ≥1 conventional biologic therapy. Pts randomised 2:1 oral 6 mg PBO twice daily (BID) stratified by baseline (BL) corticosteroid use prior exposure biologics. primary endpoint was clinical remission subscores SF ≤1 ≥1-point decrease from BL, RB=0, ES [modified, excludes friability]) at Week (Wk) 12; endoscopic response (ES ≤1) Wk 12 secondary endpoint. Results Demographic BL characteristics generally similar across groups, except for disease activity as measured modified subscore. Most (63.4%) naïve, 40.5% receiving concomitant corticosteroids (Table 1). Of 131 104 (79.4%) completed wks treatment (DEUC, 69/87 [79.3%]; PBO, 35/42 [83.3%]). At 12, rates 14.8% 16.3% arms, respectively, overall population (P=0.59); 14.0% 25.9% biologic-naïve pts; 16.1% 0.0% biologic-experienced (Figure 19.3% 27.9% (P=0.88); 15.8% 37.0% 25.8% 12.5% 2). Pharmacodynamic data suggest insufficient inhibition pathways BID. Incidence adverse events (AEs) 70.1% arm 47.6% PBO; serious AEs 9.2% (n=8) 4.8% (n=2), respectively. Rash, acne, worsening most common arm. No meaningful changes mean values laboratory parameters observed treatment. Conclusion This study BID did not meet its endpoints 12. In pts, numerically higher compared PBO. profile consistent trials psoriasis psoriatic arthritis.