S1060 Guselkumab Improves Health-Related Quality of Life in Patients With Moderately to Severely Active Ulcerative Colitis: Results From the QUASAR Phase 3 Induction Study

Introduction: The QUASAR Phase 3 Induction Study assessed the efficacy and safety of guselkumab (GUS), an IL-23 p19 subunit antagonist, as IV induction therapy in adults with moderately to severely active ulcerative colitis (UC) with an inadequate response or intolerance to conventional and/or advanced therapies (ie, TNFα antagonists, integrin receptor antagonists, or Janus kinase inhibitors). Primary outcomes were reported previously; here we report the impact of GUS vs placebo (PBO) on health-related quality of life (HRQoL) at Week (Wk) 12 as measured by the Inflammatory Bowel Disease Questionnaire (IBDQ). Methods: Patients randomly received in a blinded fashion (3:2) treatment with IV GUS 200mg or PBO at Wks 0/4/8. The primary analysis population included treated patients with a baseline modified Mayo score of 5–9 and an endoscopy subscore ≥2. The IBDQ (Total score range, 32–224) was evaluated at Wks 0/12; higher scores indicate better HRQoL, with a score ≥170 indicating disease remission (IBDQ Remission). Clinically meaningful improvements were defined using cutoffs of ≥16- or > 20-point change from baseline in IBDQ Total score. These analyses were prespecified; only IBDQ Remission at Wk 12 was controlled for analysis of multiple comparisons. Results: Seven hundred one patients were included in the primary analysis (mean age, 40.5y; male, 56.9%; mean UC duration, 7.5y; mean modified Mayo score, 6.9; Mayo endoscopy subscore of 3, 67.9%). Baseline characteristics were balanced across the GUS and PBO groups; ∼49% of each group had a prior inadequate response or intolerance to advanced therapies (ADT-IR). Mean baseline IBDQ Total scores were 125.8 and 126.3 for GUS and PBO, respectively. Compared with PBO at Wk 12, GUS was associated with greater mean reductions in IBDQ Total and each Dimension score (Bowel, Emotional, Systemic, Social; Table 1). A significantly greater ( P< 0.001) proportion of patients receiving GUS were in IBDQ Remission at Wk 12 vs PBO (51.3% vs 29.6%; adjusted treatment difference, 21.9%). The effect of GUS on IBDQ Remission was also observed in patients with or without prior ADT-IR (Table 1). A greater proportion of GUS patients achieved clinically meaningful improvements (both IBDQ improvement definitions; Figure 1). Conclusion: In patients with moderately to severely active UC, induction therapy with IV GUS 200mg resulted in higher rates of clinically meaningful IBDQ improvements and IBDQ Remission at Wk 12 vs PBO. Greater improvements were noted in each of the IBDQ domains. Table 1. - IBDQ Scores and Rates of IBDQ Remission at Wk 12 PBO IV GUS 200mg IV Treatment Difference (95% CI) IBDQ Total score change from baseline: mean (95% CI) 18.6 (14.2, 22.9) [n=261] 39.0 (35.5, 42.4) [n=405] 20.5a (15.4, 25.5) nominal P< 0.001 IBDQ Bowel score change from baseline: mean (95% CI) 7.5 (6.0, 8.9) 14.9 (13.7, 16.2) 7.3a (5.6, 9.0) nominal P< 0.001 IBDQ Emotional score change from baseline: mean (95% CI) 5.4 (3.7, 7.1) 11.6 (10.4, 12.9) 6.5a (4.6, 8.4) nominal P< 0.001 IBDQ Systemic score change from baseline: mean (95% CI) 2.6 (1.9, 3.2) 5.7 (5.1, 6.3) 3.1a (2.3, 3.9) nominal P< 0.001 IBDQ Social score change from baseline: mean (95% CI) 3.1 (2.2, 4.0) 6.7 (6.0, 7.4) 3.6a (2.6, 4.6) nominal P< 0.001 Patients in IBDQ Remission (total score ≥170) at Wk 12: % [n/N] (95% CI) 29.6% [83/280] (24.3%, 35.0%) 51.3% [216/421] (46.5%, 56.1%) 21.9%b (14.9%, 29.0%) P< 0.001 Patients with prior ADT-IR in IBDQ Remission at Wk 12: % [n/N] (95% CI) 24.3% [33/136] (17.1%, 31.5%) 39.4% [82/208] (32.8%, 46.1%) 15.2%c (5.4%, 24.9%) nominal P=0.004 Patients without prior ADT-IR in IBDQ Remission at Wk 12: % [n/N] (95% CI) 34.7% [50/144] (26.9%, 42.5%) 62.9% [134/213] (56.4%, 69.4%) 28.2%c (18.1%, 38.3%) nominal P< 0.001 NOTE: Patients who had a prohibited change in UC medication, an ostomy or colectomy, or discontinued study agent due to lack of efficacy or an AE of worsening of UC or other reasons except for COVID-19 reasons (excluding COVID-19 infection) or regional crisis in Russia and Ukraine, had their baseline value carried forward and were considered not in IBDQ Remission. Patients missing an IBDQ Total score at Wk 12 were considered not in IBDQ Remission.aTreatment difference estimated by the difference in the least squares means (ANCOVA); P-value based on ANCOVA.bAdjusted treatment difference based on the Wald statistic with Cochran-Mantel-Haenszel (CMH) weight; P-value based on CMH chi-square test, stratified by ADT-inadequate response/intolerance (ADT-IR) status (Yes/No) and concomitant use of corticosteroids at baseline (Yes/No).cAdjusted treatment difference based on the Wald statistic with CMH weight; P-value based on CMH chi-square test, stratified by concomitant use of corticosteroids at baseline (Yes/No). Figure 1.: Percentage of patients with ≥16- or >20-point IBDQ Total score improvements at Wk 12.

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