P378 Changes in Simplified Endoscopic Score for Crohn’s disease (SES-CD) during a 16-week induction treatment with upadacitinib: analysis of the randomised controlled CELEST study

Abstract

Background: The SES‐CD is a validated and widely used outcome measure in clinical trials. We assessed the efficacy of upadacitinib (UPA), an oral selective JAK1 inhibitor, on mucosal inflammation in different disease phenotypes using SES‐CD segmental scores. Methods: CELEST (NCT02365649) was a placebo (PBO)‐controlled Phase 2 study in adults with moderate to severe CD refractory or intolerant to immunosuppressants and/or biologics. Patients were randomised to PBO or UPA 3 mg, 6 mg, 12 mg, or 24 mg twice daily (BID) or 24 mg once daily (QD) for 16 weeks. Ileocolonoscopy was done at baseline and either Week 12 or 16. This analysis evaluated changes from baseline to Week 12/16 in total SES‐CD and its components (size of ulcers, ulcerated surface, affected surface, presence of narrowing) in the overall population and by disease location (ileal, colonic, ileocolonic [based on centrally‐read endoscopic scores at baseline]). Statistical difference was analysed via ANCOVA at p = 0.1 level. Results: Of 220 randomised patients, most were female (57%) with disease duration >3 years (88%) and mean age 40.7 years. Most patients (n = 114) had ileocolonic disease at baseline (table). In the overall population, mean (SD) change from baseline to Week 12/16 in total SES‐CD was significantly greater with UPA 6 mg (‐3.9 [6.3]; p = 0.006; n = 33), 12 mg (‐3.9 [9.8]; p = 0.005; n = 27), 24 mg BID (‐5.7 [6.0]; p < 0.001; n = 29), and 24 mg QD (‐3.9 [7.2]; p = 0.003; n = 31) vs. PBO (0.4 [7.3]; n = 26). SES‐CD subscores were generally significantly improved with UPA vs. PBO except for presence of narrowing (Figure). When assessed by disease location, mean (SD) changes from baseline to Week 12/16 in total SES‐CD were significantly greater with UPA 12 mg (‐7.5 [9.4]; p = 0.099; n = 8) and 24 mg BID (‐7.9 [7.2]; p = 0.025; n = 11) vs. PBO (4.3 [9.3]; n = 3) in patients with colonic disease and with 6 mg (‐5.5 [6.5]; p = 0.023; n = 17), 12 mg (‐3.1 [10.7]; p = 0.079; n = 17), and 24 mg BID (‐5.1 [5.0]; p = 0.018; n = 14) and 24 mg QD (‐6.8 [5.4]; p = 0.005; n = 14) vs. PBO (‐0.3 [8.0]; n = 18) in patients with ileocolonic disease. No significant differences were observed for UPA (n = 3‐9) vs. PBO (n = 5) in patients with ileal disease. Conclusions: UPA induction treatment at doses ≥6 mg BID significantly improved total SES‐CD vs. PBO, with improvements in all subscores except for presence of narrowing. (Table Presented).