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Abstract Background Patients with Crohn’s disease (CD) experience reduced quality of life (QoL), and disease-related impact on work productivity, contributing to a high disease burden. This study evaluated the association of achieving endoscopic outcomes at week 12 and associated QoL at week 52 in patients with CD treated with upadacitinib (UPA). Methods This post-hoc analysis evaluated data from two Phase 3 UPA induction (U-EXCEED and U-EXCEL) trials and one maintenance (U-ENDURE) trial in patients with moderate to severe CD. Patients who responded to 12-week induction therapy with UPA (45 mg per day [QD]) in U-EXCEED or U-EXCEL and received maintenance therapy with UPA (15 or 30 mg QD) up to 52 weeks in U-ENDURE were included. Meaningful improvement in QoL outcomes (Inflammatory Bowel Disease Questionnaire [IBDQ] remission ≥170, IBDQ response increase ≥16, Functional Assessment of Chronic Illness Therapy – Fatigue [FACIT-F] response increase ≥9, Short Form 36 [SF-36] Physical Component Score [PCS] and Mental Component Score [MCS] change ≥5, and Work Productivity and Activity Impairment Questionnaire [WPAI] change ≥7%) was evaluated at week 52 and compared between patients who achieved endoscopic response, endoscopic remission and ulcer-free endoscopy (absence of ulceration) at week 12 and those who did not using Chi-square test. Results Of 337 clinical responders included in the analyses, 152 (45.1%), 87 (25.8%), and 75 (22.2%) patients achieved endoscopic response, endoscopic remission, and ulcer-free endoscopy, respectively, at the end of induction. Significantly more patients who achieved an endoscopic response at end of induction (vs those who did not) attained a meaningful improvement in PROs by week 52 (IBDQ remission, 52.6% vs 30.3%; IBDQ response, 56.6% vs 36.8%; FACIT-F response, 46.7% vs 25.9%; SF-36 PCS 49.3% vs 30.8% and MCS 39.5% vs 25.9%; all P≤0.01, Table 1). Additionally, patients who achieved endoscopic response (vs those who did not) at the end of induction were more likely to attain meaningful improvement in WPAI overall work impairment by week 52 (47.1% vs 26.5%, P≤0.01, Table 1). Similar findings were observed in patients who achieved endoscopic remission (P≤0.01, Table 1) and ulcer-free endoscopy (P≤0.05, Table 1) vs those who did not at end of induction. Conclusion Achieving endoscopic outcomes at end of induction treatment was associated with meaningful improvement in quality of life and overall work productivity at 52 weeks for patients with CD receiving UPA. Endoscopic remission and ulcer-free endoscopy were associated with very similar long-term benefit.

SummaryBackgroundCrohn's disease has a substantial negative impact on health‐related quality of life (HRQoL).AimTo examine the effects of risankizumab on HRQoL in Crohn's diseaseMethodsWe analysed data from patients with Crohn's disease from 12‐week induction trials ADVANCE (N = 850) and MOTIVATE (N = 569) with risankizumab 600 mg or 1200 mg intravenous (IV) versus placebo IV and a 52‐week maintenance trial FORTIFY (N = 462) with risankizumab 180 or 360 mg subcutaneous (SC) versus placebo SC. Outcomes included Inflammatory Bowel Disease Questionnaire (IBDQ), Functional Assessment of Chronic Illness Therapy‐Fatigue (FACIT‐F), 36‐item Short Form Health Survey (SF‐36), EuroQol 5‐Dimension‐5‐Level (EQ‐5D‐5L) and work productivity. The mean change and percentages of patients achieving clinically meaningful improvement in all outcomes were determined at weeks 12 and 52.ResultsAt week 12, more patients in the risankizumab 600 or 1200 mg groups achieved IBDQ response than with placebo (ADVANCE: 70.2%, 75.5% vs. 47.8%, p ≤ 0.001; MOTIVATE: 61.7%, 68.5% vs. 48.2%, p ≤ 0.01) and FACIT‐F response (ADVANCE: 51.3%, 48.0% vs. 35.7%, p ≤ 0.01; MOTIVATE: 44.2%, 49.1% vs. 33.7%, p < 0.05). These improvements persisted at week 52 with risankizumab maintenance treatment. Similar trends were observed for SF‐36 physical and mental component summary scores, EQ‐5D‐5L and activity impairment within work productivity measures.ConclusionsRisankizumab induction therapy (600 or 1200 mg IV) led to clinically meaningful improvements in disease‐specific and general patient‐reported outcomes, including fatigue, in patients with moderate to severe Crohn's disease. These improvements were sustained after 52 weeks of risankizumab (180 or 360 mg SC) maintenance therapy.

Abstract Background and Aims Bowel urgency and abdominal pain are impactful, yet under-appreciated ulcerative colitis symptoms and not commonly assessed in clinical trials. We evaluated how these symptoms may improve with upadacitinib treatment and correlate with clinical and health-related quality of life [HRQOL] outcomes in the phase 2b U-ACHIEVE study. Methods Patients aged 18–75 years, with moderately to severely active ulcerative colitis, were randomised to receive placebo or upadacitinib (7.5, 15, 30, or 45 mg once daily [QD]). Bowel urgency and abdominal pain were evaluated at baseline and Weeks 2, 4, 6, and 8. Week 8 correlations were evaluated between bowel urgency/abdominal pain with clinical [Mayo subscores and high-sensitivity C-reactive protein and faecal calprotectin measurements] and HRQOL outcomes [Inflammatory Bowel Disease Questionnaire and 36-Item Short Form Health Survey scores]. Results A greater proportion of patients [n = 250] reported no bowel urgency and less abdominal pain with upadacitinib treatment compared with placebo, with improvements observed as early as 2 weeks. At Week 8, patients receiving the 45-mg QD dose had the greatest improvements versus placebo, with 46% reporting no bowel urgency [vs 9%; p ≤ 0.001] and 38% reporting no abdominal pain [vs 13%; p = 0.015]. At Week 8, moderate correlations were found between bowel urgency or abdominal pain and most clinical and HRQOL outcomes. Conclusions Induction treatment with upadacitinib demonstrated significant reductions in bowel urgency and abdominal pain compared with placebo. These symptoms also correlate to clinical and HRQOL outcomes, supporting their use to monitor disease severity and other treatment outcomes.

Abstract Background Risankizumab (RZB), an IL-23 inhibitor, is being investigated for Crohn’s disease (CD). MOTIVATE (NCT03105128) and ADVANCE (NCT03104413) were two double-blind, randomised, placebo (PBO)-controlled phase 3 trials evaluating the efficacy and safety of RZB as induction therapy for CD after inadequate response or intolerance to biologic treatment, or conventional or biologic treatment. We investigated the effect of RZB on patient-reported outcomes (PROs) in these two trials. Methods Patients with moderately to severely active CD (CD activity index of 220–450, Simple Endoscopic Score for CD excluding the narrowing component ≥ 6 or ≥ 4 for isolated ileal disease, and average daily stool frequency ≥ 4 and/or average daily abdominal pain score ≥ 2) were randomised 1:1:1 (MOTIVATE; N=569) or 2:2:1 (ADVANCE; N=850) to intravenous RZB 600 mg, RZB 1200 mg or PBO at Weeks 0, 4 and 8. PROs assessed were Inflammatory Bowel Disease Questionnaire (IBDQ), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), and 36-Item Short Form Health Survey (SF 36). Least-squares mean change from baseline to Week 4 and 12 were assessed for each PRO. Additionally, the proportion of patients achieving IBDQ remission (IBDQ total score ≥ 170 points) was evaluated. Comparisons between RZB dosage groups and PBO were based on Cochran-Mantel-Haenszel or chi-square/Fisher’s exact tests; missing data were reported using non-responder imputation. Results In the MOTIVATE (100% biologic inadequate responder [bio-IR]) and ADVANCE (57% bio-IR) trials, significant (P&lt;0.05) improvements in nearly all PROs evaluated were seen as early as Week 4 (Figures 1–4). At Week 12, significant improvements in all PROs were reported for both doses of RZB compared with PBO in both trials, except for the SF-36 Mental Component Summary score (RZB 1200 mg in MOTIVATE), which improved, but not significantly. In MOTIVATE, at Week 4 and 12, IBDQ remission was achieved by significantly (P&lt;0.05) more patients taking RZB (600 mg, 25.1%/38.3%; RZB 1200 mg, 31.9%/44.6%) than PBO (15.5%/26.8%). Results were similar in ADVANCE: RZB 600 mg 30.9%/44.5%, RZB 1200 mg 33.7%/51.5%, and PBO 18.4%/29.8% at weeks 4 and 12, respectively (P&lt;0.001 for both RZB groups compared to PBO). Conclusion Patients with active CD and an inadequate response to conventional or biologic treatment who received RZB (600 mg or 1200 mg) induction therapy reported significant improvements in disease-specific (IBDQ) and general health-related PROs (FACIT and SF-36) compared with PBO, with improvements seen as early as Week 4. Funding statement: Study was funded by AbbVie. Acknowledgement: Medical writing support was provided by Joann Hettasch of Fishawack Facilitate Ltd, and was funded by AbbVie.