S857 Patient-Reported Outcomes of Response and Remission Following Guselkumab Induction Treatment as Measured by the Inflammatory Bowel Disease Questionnaire: Results Through Week 12 of the Phase 2 GALAXI 1 Study

Abstract

Introduction: GALAXI 1 is a phase 2, double-blind, placebo-controlled study of guselkumab (GUS), an IL-23 antagonist, for the treatment of patients (pts) with moderately to severely active Crohn’s disease (CD) who had inadequate response or intolerance to conventional therapies (corticosteroid, immunosuppressant) and/or biologics (TNF antagonist, vedolizumab). Patient-reported outcomes from the Inflammatory Bowel Disease Questionnaire (IBDQ) through Week (Wk) 12 following GUS induction are reported here for the interim analysis population. Methods: Pts with moderate to severe CD (CDAI score 220-450) were randomized 1:1:1:1:1 to GUS 200, 600, or 1200mg IV at Wks 0, 4, 8; ustekinumab (UST) ∼6mg/kg IV at Wk 0 and 90mg SC at Wk 8; or placebo (PBO) IV. The IBDQ is a 32-item questionnaire with 4 dimensions: bowel symptoms, emotional function, systemic symptoms, and social function. IBDQ scores range from 32 to 224 with higher scores indicating better quality of life. IBDQ scores were evaluated at Wk 8 and Wk 12 for change from baseline, IBDQ response (defined as ≥16-point improvement from baseline), and IBDQ remission (defined as IBDQ score ≥170) for the GUS combined and PBO treatment groups. UST was a reference arm. Results: Two hundred fifty pts were evaluated; approximately 50% failed previous biologic therapy. Baseline demographics and disease characteristics were generally similar across treatment groups. However, some differences were observed between the groups, the most notable of which included a slightly lower disease duration in the GUS 1200mg IV group (6.2 yrs) compared with the GUS 200mg IV group (11.7 yrs), and a lower mean baseline IBDQ total score in the PBO group (117.3) compared with the GUS combined and UST groups. IBDQ scores change from baseline at Wk 8 and Wk 12 are presented in Table 1. Mean change from baseline in total IBDQ and each of the 4 IBDQ domains was greater among pts in the combined GUS group compared with the PBO group. The proportion of pts who achieved IBDQ response at Wk 8 and Wk 12 was higher in the combined GUS treatment group compared with PBO (Figure 1). A similar trend was seen for IBDQ remission. Conclusion: In pts with moderately to severely active CD, pts treated with GUS (combined) induction therapy reported greater improvement in IBDQ scores compared with PBO as early as Wk 8. A higher proportion of pts treated with GUS compared with PBO achieved IBDQ response and remission at Wks 8 and 12, and this treatment benefit (as delta) increased from Wk 8 to Wk 12.Table 1.: Change from baseline in IBDQ total and domain scores, at Week 8 and Week 12.Figure 1.: IBDQ Response and IBDQ Remission at Week 8 and Week 12.