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
Danese, S.(1);Panaccione, R.(2);D'Haens, G.(3);Peyrin-Biroulet, L.(4);Schreiber, S.(5);Kobayashi, T.(6);Gawdis-Wojnarska, B.(7);Korga, P.(8);Aguilar, H.(9);Sharkey, B.(10);Sreih, A.(11);Radosti, C.(10);Patel, A.(10);Canavan, J.(10);Rubin, D.(12);
(1)Humanitas Research Hospital, Inflammatory Bowel Diseases Center, Milan, Italy;(2)University of Calgary, Inflammatory Bowel Disease Clinic, Calgary- Alberta, Canada;(3)Amsterdam University Medical Centers, Inflammatory Bowel Disease Unit, Amsterdam, Netherlands Antilles;(4)Nancy University Hospital, Gastroenterology, Nancy, France;(5)University Hospital Schleswig-Holstein, Gastroenterology, Kiel, Germany;(6)Kitasato University Kitasato Institute Hospital, Gastroenterology, Tokyo, Japan;(7)Twoja Przychodnia-Szczecińskie Centrum Medyczne, Gastroenterology, Szczecin, Poland;(8)Centrum Medyczne KERmed, Gastroenterology, Bydgoszcz, Poland;(9)Louisiana Research Center, Gastroenterology, Shreveport, United States;(10)Bristol Myers Squibb, Division of Immunology and Fibrosis Development, Princeton, United States;(11)Bristol Myers Squibb, Department of Immunology and Fibrosis Development, Princeton, United States;(12)University of Chicago Medicine, Inflammatory Bowel Disease Center, Chicago, United States;
Background
Tyrosine kinase 2 (TYK2) is an intracellular kinase that mediates the signalling of key cytokines involved in ulcerative colitis (UC) pathophysiology. Deucravacitinib (DEUC) is a novel, oral, selective TYK2 inhibitor that binds to the TYK2 regulatory domain. The safety and efficacy of DEUC were evaluated in patients (pts) with moderately-to-severely active UC.
Methods
LATTICE-UC (NCT03934216), a randomised, double-blind, placebo (PBO)-controlled, multicentre, Phase 2 trial, enrolled pts with moderately-to-severely active UC (modified Mayo score of 5 to 9 [endoscopic {ES} subscore ≥2, rectal bleeding {RB} subscore ≥1, stool frequency {SF} subscore ≥2) with inadequate response, loss of response, or intolerance to ≥1 conventional or biologic therapy. Pts were randomised 2:1 to oral DEUC 6 mg or PBO twice daily (BID) and stratified by baseline (BL) corticosteroid use and prior exposure to biologics. The primary endpoint was clinical remission (modified Mayo score with subscores of SF ≤1 with ≥1-point decrease from BL, RB=0, and ES ≤1 [modified, excludes friability]) at Week (Wk) 12; endoscopic response (ES ≤1) at Wk 12 was a secondary endpoint.
Results
Demographic and BL characteristics were generally similar across groups, except for BL disease activity as measured by the modified Mayo score and ES subscore. Most pts (63.4%) were biologic naïve, and 40.5% were receiving concomitant oral corticosteroids (Table 1). Of 131 pts randomised, 104 (79.4%) completed 12 wks of treatment (DEUC, 69/87 [79.3%]; PBO, 35/42 [83.3%]). At Wk 12, clinical remission rates were 14.8% and 16.3% in the DEUC and PBO arms, respectively, in the overall population (P=0.59); 14.0% and 25.9% in biologic-naïve pts; and 16.1% and 0.0% in biologic-experienced pts (Figure 1). At Wk 12, endoscopic response rates were 19.3% and 27.9% in the DEUC and PBO arms, respectively, in the overall population (P=0.88); 15.8% and 37.0% in biologic-naïve pts; and 25.8% and 12.5% in biologic-experienced pts (Figure 2). Pharmacodynamic data suggest insufficient inhibition of TYK2 pathways with DEUC 6 mg BID. Incidence of adverse events (AEs) was 70.1% in the DEUC arm and 47.6% with PBO; rates of serious AEs were 9.2% (n=8) and 4.8% (n=2), respectively. Rash, acne, and worsening of UC were the most common AEs in the DEUC arm. No meaningful changes from BL in mean values of laboratory parameters were observed with DEUC treatment.
Conclusion
This Phase 2 study of DEUC 6 mg BID in moderately-to-severely active UC did not meet its primary or secondary efficacy endpoints at Wk 12. In biologic-experienced pts, response rates were numerically higher with DEUC compared with PBO. The safety profile was consistent with DEUC trials in psoriasis and psoriatic arthritis.
