B0375 - Efficacy and Safety of Upadacitinib Induction Therapy in Patients With Moderately to Severely Active Crohn’s Disease: Results From a Randomized Phase 3 U-EXCEL Study

Introduction: Eligible patients(N=526) with moderate to severe active Crohn’s Disease(CD), defined as average daily stool frequency(SF)≥4 and/or abdominal pain score(APS)≥2, and a Simple Endoscopic Score for CD(SES-CD) (excluding the narrowing component subscore) ≥6(≥4 for subjects with isolated ileal disease).

Methods: Patients(pts) were randomized 2:1 to UPA45 or PBO for 12 weeks(wks). Pts on baseline corticosteroids(CS) initiated a protocolized tapering at wk4. The co-primary endpoints, clinical remission(per CDAI for US [CDAI< 150] or per SF/APS for EU [average daily SF ≤2.8 and APS≤1.0 and neither greater than baseline [BL]) and endoscopic response(decrease in SES-CD >50% from BL or ≥2-point reduction from BL for pts with a BL SES-CD=4), were evaluated at wk 12. Safety, primary and key secondary clinical, and endoscopic outcomes were evaluated through wk 12.

Results: BL demographics and characteristics were similar between groups; 45.4% of pts had a history of prior biologic use or failure. At wk 12, significantly more pts receiving UPA45 vs PBO achieved the co-primary endpoints: clinical remission(per CDAI, UPA45 49.5% vs PBO 29.1%; per SF/APS, UPA45 50.7% vs PBO 22.2%) and endoscopic response (UPA45 45.5% vs PBO 13.1%) (P< .0001 for all endpoints; Table 1). UPA45 was superior to PBO for most of the ranked secondary endpoints including clinical remission per CDAI and SF/APS at wk 4, CS-free clinical remission per CDAI and SF/APS at wk 12, clinical response(CR-100; 100-point decrease in CDAI from BL at wk 2 and wk 12, and endoscopic remission at wk 12(P< .0001 or P< .01, Table 1). Severe AEs occurred at 8.9% and 8.5% within UPA45 and PBO groups, respectively. The most common AEs(≥5% of pts) were acne and anemia among pts treated with UPA, and CD exacerbation among pts receiving PBO. Serious infections were 1.1% and 1.7% for UPA45 and PBO groups, respectively. Herpes zoster(2.9%) was reported in the UPA45 group only, and an adjudicated cardiovascular event(0.6%) was reported only in the PBO group. No treatment-emergent deaths, malignancies, other opportunistic infections, adjudicated gastrointestinal perforations or adjudicated thrombotic events were reported in either group.

Discussion: UPA45 induction therapy was superior to PBO in achieving early response, including clinical remission, endoscopic response, and CS-free clinical remission during the U-EXCEL study. UPA45 was well tolerated, with no new safety risks and a safety profile comparable to previous UPA studies.