Total Inflammatory Bowel Disease Questionnaire Score Research Articles

Health-Related Quality of Life Outcomes With Etrasimod Treatment in Patients With Ulcerative Colitis: A Post Hoc Analysis of Data From ELEVATE UC 52 and ELEVATE UC 12.

Etrasimod is an oral, once-daily (QD), selective sphingosine 1-phosphate1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). Here, we evaluate the impact of etrasimod 2mg QD on health-related quality of life (HRQoL) in patients with UC. This post hoc analysis used data from the Phase 3 randomized controlled trials, ELEVATE UC 52 and ELEVATE UC 12. HRQoL measures included: Inflammatory Bowel Disease Questionnaire (IBDQ), 36-Item Short Form Survey (SF-36), and Work Productivity and Activity Impairment Questionnaire: Ulcerative Colitis (WPAI:UC) completed at baseline, Week 12 (both trials), and Week 52 (ELEVATE UC 52 only). For IBDQ analyses, patients were stratified by prior exposure to biologics/Janus kinase inhibitors (JAKi) and baseline modified Mayo score (MMS; 4-6 or 7-9). Generally, significantly greater proportions of patients receiving etrasimod (N = 527) vs placebo (N = 260) achieved IBDQ remission (IBDQ total score ≥170) and IBDQ response (IBDQ total score increase from baseline ≥16), with significant improvement in all IBDQ domain scores at Week 12 and maintained through Week 52. Significant differences in IBDQ remission and IBDQ response rates between etrasimod and placebo were more consistent among biologic/JAKi-naive patients vs those who were biologic/JAKi-experienced and in those with baseline MMS 7-9 vs 4-6. Significant improvements were observed in several SF-36 domain and summary scores and WPAI:UC domain scores at Week 12 and Week 52. Etrasimod 2mg QD demonstrated significant and clinically meaningful improvements across multiple HRQoL measures, including WPAI, vs placebo. ClinicalTrials.gov: NCT03945188; NCT03996369.

Impact of Kono-S anastomosis on quality of life after ileocolic resection in Crohn's disease: an analysis from the SuPREMe-CD trial.

Crohn's disease has debilitating effects on patients' quality of life. Currently, there are limited data on the effect of anastomotic configuration on health-related quality of life after ileocaecal resection for Crohn's disease. This study aimed to assess the impact of Kono-S anastomosis on quality of life after ileocolic resection, compared to the conventional side-to-side anastomosis. Patients with primary or recurrent Crohn's disease participating in the ongoing SuPREMe-CD trial were interviewed about quality of life using the Inflammatory Bowel Disease Questionnaire (IBDQ). The primary endpoint was disease-specific quality of life, assessed with IBDQ. Secondary outcomes were quality of life related to bowel symptoms, systemic symptoms, social function and emotional function. Of the 94 patients included, 51 (54%) received the conventional side-to-side anastomosis and 43 (46%) the Kono-S anastomosis. Demographics were comparable between the two groups. The IBDQ was assessed at a mean follow-up of 54.0 ± 18.7 months from surgical intervention. The mean total IBDQ score was 155.1 ± 28.07 in the conventional group and 163.8 ± 25.23 in the Kono-S group (P = 0.11). When considering bowel symptoms and social function, mean scores were 50.7 and 23.5 in the conventional group, and 56.3 and 26.5 in the Kono-S group (P = 0.002 and P = 0.02, respectively). Kono-S anastomosis was independently associated with improved quality of life regarding bowel symptoms (P = 0.006) and social function (P = 0.03) after correcting for other confounding factors on linear regression analysis. Compared to conventional side-to-side anastomosis, patients with Kono-S anastomosis presented significantly better bowel symptoms and social function scores at 54 months after surgery.

Structured Reporting of Computed Tomography Enterography in Crohn's Disease.

To compare the integrity, clarity, conciseness, etc., of the structured report (SR) versus free-text report (FTR) for computed tomography enterography of Crohn's disease (CD). FTRs and SRs were generated for 30 patients with CD. The integrity, clarity, conciseness etc., of SRs versus FTRs, were compared. In this study, an evidence-based medicine practice model was utilized on 92 CD patients based on SR in order to evaluate its clinical value. Then, the life quality of the patients in two groups was evaluated before and after three months of intervention using an Inflammatory Bowel Disease Questionnaire (IBDQ). SRs received higher ratings for satisfaction with integrity (median rating 4.27 vs. 3.75, P=0.008), clarity (median rating 4.20 vs. 3.43, P=0.003), conciseness (median rating 4.23 vs. 3.20, P=0.003), the possibility of contacting a radiologist to interpret (median rating 4.17 vs. 3.20, P<0.001), and overall clinical impact (median rating 4.23 vs. 3.27, P<0.001) than FTRs. Besides, research group had higher score of IBDQ intestinal symptom dimension (median score 61.13 vs. 58.02, P=0.003), IBDQ systemic symptom dimension (median score 24.48 vs. 20.67, P<0.001), IBDQ emotional capacity dimension (median score 65.65 vs. 61.74, P<0.001), IBDQ social ability dimension (median score 26.80 vs. 22.37, P<0.001), and total IBDQ score (median score 178.07 vs. 162.80, P<0.001) than control group. The SR of CTE in CD patients was conducive to improving the quality and readability of the report, and CD patients' life quality could significantly improve after the intervention of an evidence-based medicine model based on SR.

A31 MIRIKIZUMAB IMPROVES QUALITY OF LIFE IN MODERATELY-TO-SEVERELY ACTIVE UC: IMPROVEMENT IN IBDQ SCORES IN PARTICIPANTS OF LUCENT-1 AND LUCENT-2 RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED PHASE 3 TRIALS

A31 MIRIKIZUMAB IMPROVES QUALITY OF LIFE IN MODERATELY-TO-SEVERELY ACTIVE UC: IMPROVEMENT IN IBDQ SCORES IN PARTICIPANTS OF LUCENT-1 AND LUCENT-2 RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED PHASE 3 TRIALS

P465 Health-related quality of life from the Inflammatory Bowel Disease Questionnaire in patients with ulcerative colitis treated with etrasimod in the phase 3 ELEVATE UC 52 and ELEVATE UC 12 trials

Abstract Background Etrasimod is an investigational, once-daily, oral, selective sphingosine 1-phosphate receptor 1,4,5 modulator (S1P1,4,5) in development for the treatment of moderately to severely active ulcerative colitis (UC). ELEVATE UC 52 and ELEVATE UC 12 were two phase 3 studies that demonstrated efficacy and safety of etrasimod in patients with UC in which several patient-reported outcomes were collected. Health-related quality of life (HRQoL) was assessed in a post hoc analysis of the ELEVATE programme with the validated Inflammatory Bowel Disease Questionnaire (IBDQ).1 Methods In ELEVATE UC 52 (NCT03945188) and ELEVATE UC 12 (NCT03996369), patients (16-80 years) with moderately to severely active UC were randomised 2:1 to once-daily etrasimod 2 mg or placebo (PBO). Patients in the full analysis set with modified Mayo Scores 5-9 with a completed 32-item IBDQ questionnaire at baseline, week 12 (both trials) and week 52 (ELEVATE UC 52 only) were included in this analysis. Least squares mean (LSM) change from baseline for IBDQ total score and IBDQ domain scores were compared between etrasimod and PBO arms in both trials at each time point (data as observed), along with the proportion of patients who achieved IBDQ remission (IBDQ total score ≥170; nonresponder imputation). Results At baseline, a total of 237 and 191 etrasimod-treated patients and 112 and 96 PBO-treated patients completed the IBDQ for ELEVATE UC 52 and ELEVATE UC 12, respectively. LSM change from baseline in IBDQ total scores for etrasimod vs PBO were 42.8 vs 27.4 (difference [95% CI] 15.4 [6.5, 24.4]; P&amp;lt;0.001) and 55.8 vs 38.1 (difference [95% CI] 17.7 [6.6, 28.6]; P=0.002) at week 12 and week 52, respectively, in ELEVATE UC 52, and 47.5 vs 30.2 (difference [95% CI] 17.3 [8.5, 26.2]; P&amp;lt;0.001) at week 12 in ELEVATE UC 12 (Figure 1A). A greater proportion of etrasimod-treated patients achieved IBDQ remission at week 12 in both trials and week 52 in ELEVATE UC 52 (Figure 1B). Etrasimod-treated patients demonstrated significant improvements from baseline vs PBO in all 4 IBDQ domains in both trials (Figure 2). Across all IBDQ domains, improvements were seen at 12 weeks and the LSM change from baseline was greatest among etrasimod-treated patients at all time points. Conclusion Patients treated with etrasimod demonstrated greater improvement from baseline in total and all 4 domain scores of the IBDQ at the end of the 12-week induction phase and 52-week maintenance phase in comparison with PBO. These findings demonstrate the benefits of etrasimod on disease-specific HRQoL and support the clinical findings from the ELEVATE programme. Reference: 1. Chen XL, et al. Health Qual Life Outcomes. 2017;15:1-13.

P391 Relative association of bowel urgency clinically meaningful improvement or bowel urgency remission versus stool frequency remission and rectal bleeding remission with improvement in Inflammatory Bowel Disease Questionnaire scores in patients with moderately-to-severely active Ulcerative Colitis: An analysis from LUCENT-1 and LUCENT-2 phase 3 clinical trials

Abstract Background Bowel urgency is increasingly being recognized as an impactful symptom in patients with ulcerative colitis (UC)1. However, limited information is available regarding its potential association with other patient reported outcomes. We assessed the association of bowel urgency clinically meaningful improvement (CMI) or bowel urgency remission with Inflammatory Bowel Disease Questionnaire (IBDQ) scores whilst adjusting for the potential confounding effects of stool frequency (SF) and rectal bleeding (RB) remission using data from LUCENT-1 (NCT03518086) and LUCENT-2 (NCT03524092) phase 3 trials. Methods Bowel urgency severity was assessed by the Urgency Numeric Rating Scale (UNRS) (0=no urgency to 10=worst possible urgency). Bowel urgency CMI was defined as ≥3-point decrease in UNRS compared to baseline and bowel urgency remission was defined as UNRS of 0 or 1.2 IBDQ scores (range: 32–224) were calculated; higher scores indicate better quality of life. Mediation analyses were performed to examine the relative association between direct effects of bowel urgency CMI and bowel urgency remission (separate predictors) and IBDQ scores while adjusting for the potential confounding effects of SF remission and RB remission (mediators). Analyses were treatment agnostic and combined patients from mirikizumab and placebo groups from LUCENT-1 (N=1162) and LUCENT-2 (N=544) trials at Week (W) 12 and 40 (W52 of continuous treatment). Results At W12 and W52, bowel urgency remission directly accounted for 44.8% and 32.5% improvement in IBDQ total score, respectively; 22.7% and 39.1% of improvement was mediated by RB remission and 32.5% and 28.4% by SF remission, respectively. At W12, bowel urgency remission resulted in the largest proportion of improvement in each of the IBDQ domain subscores, whereas at W52, RB remission had a greater confounding effect (Fig. 1A). At W12 and W52, bowel urgency CMI accounted for 70% and 57.3% improvement in IBDQ total score, respectively; 12.8% and 25.6% of effects were mediated by RB remission and 17.2% and 17.1% by SF remission, respectively (Fig. 1B). Bowel urgency CMI accounted for the largest proportion of association with improvement in each of the IBDQ domain subscores at both W12 and W52. Conclusion Improvements in IBDQ scores were primarily ascribed to bowel urgency remission and bowel urgency CMI relative to RB remission and SF remission, particularly at W12, in patients with moderately-to-severely active UC. These findings suggest that bowel urgency is a critical and independent symptom that considerably impacts patients’ quality of life.

S16 Association of Quality of Life With Clinical Remission, HEMR, and Bowel Urgency in Patients With Ulcerative Colitis Treated With Mirikizumab

Background: Mirikizumab, a p19-directed anti-IL-23 antibody, has demonstrated efficacy and safety in patients with moderately-to-severely active ulcerative colitis (UC) in the Phase 3 LUCENT-1 induction trial (NCT03518086) and LUCENT-2 maintenance trial (NCT03524092). Secondary analyses of LUCENT trials showed that mirikizumab treated patients had significantly improved quality of life compared to patients with placebo. This analysis evaluated the relationships between quality of life assessed by the Inflammatory Bowel Disease Questionnaire (IBDQ) and patients’ status of achieving clinical remission, histologic-endoscopic mucosal remission (HEMR), bowel urgency clinically meaningful improvement (CMI), and bowel urgency remission. Methods: In LUCENT-1, 1,281 patients were randomized 3:1 to mirikizumab 300 mg intravenous infusion or placebo every 4 weeks (Q4W). Patients who achieved clinical response to mirikizumab by Week 12 (W12) of induction (N=544), were re-randomized 2:1 to subcutaneous mirikizumab 200mg or placebo Q4W for 40 weeks in LUCENT-2 (52-weeks of continuous treatment). The primary endpoint was proportion of patients with clinical remission at W12 in LUCENT-1 and Week 40 in LUCENT-2. The clinical outcomes of interest in this analysis include: IBDQ (a 32-item patient-completed questionnaire with higher scores indicating better disease-specific quality of life ), clinical remission (stool frequency subscore = 0 or 1 with a ≥1-point decrease from baseline; rectal bleeding subscore = 0; and endoscopic subscore (ES)= 0 or 1), HEMR (Geboes score of ≤2B and ES = 0 or 1), and bowel urgency [assessed using the Urgency Numeric Rating Scale (UNRS), a 11-point scale ranging from 0 (“no urgency”) to 10 (“worst possible urgency”)]. Bowel urgency CMI is a ≥3-point change and bowel urgency remission is a UNRS score of 0 or 1, both among patients with a baseline UNRS of ≥3. Association between IBDQ total score change from baseline and clinical outcomes were assessed at W12 and Week 52 (W52) using analysis of covariance models adjusting for treatment, clinical parameter, baseline IBDQ value, and randomization stratification factors. Results: Overall, significantly greater increase in IBDQ total score were observed in patients who achieved clinical remission, HEMR, bowel urgency CMI or bowel urgency remission compared to those who did not. As for patients treated with mirikizumab, the least square mean (LSM) change of IBDQ total score [LSM(SE)] by clinical outcome status (Yes vs No) were: Clinical Remission: W12: 55.0 (2.02) vs 33.7 (1.16), P< 0.001; W52: 60.7 (2.38) vs 39.8 (2.43), P< 0.001; HEMR: W12: 50.3 (2.15) vs 35.2 (1.19), P< 0.001; W52: 59.3 (2.60) vs 43.4 (2.40), P< 0.001; Bowel Urgency CMI: W12: 52.8 (1.41) vs 27.4 (1.36), P< 0.001; W52: 62.5 (2.20) vs 34.4 (2.77), P< 0.001; and Bowel Urgency Remission: W12: 57.6 (1.92) vs 32.3 (1.15), P< 0.001; W52: 64.9 (2.54) vs 40.8 (2.18), P< 0.001. Placebo-treated patients were similar to the mirikizumab group across the studied clinical outcomes endpoints, with smaller magnitude of IBDQ improvements. Conclusion(s): The achievement of clinical remission, histologic-endoscopic mucosal remission, bowel urgency clinically meaningful improvement and bowel urgency remission was associated with significant improvement in quality of life by IBDQ in patients with UC from LUCENT-1 and 2 trials.

Health-Related Quality of Life Outcomes With Tofacitinib Treatment in Patients With Ulcerative Colitis in the Open-Label Extension Study, OCTAVE Open.

Tofacitinib is an oral small molecule Janus kinase inhibitor for the treatment of ulcerative colitis. We report health-related quality of life (HRQoL) outcomes in patients with ulcerative colitis in the phase 3 open-label, long-term extension study, OCTAVE Open. The Inflammatory Bowel Disease Questionnaire (IBDQ), EuroQoL-5 Dimensions Health Questionnaire, and 36-Item Short Form Survey scores were analyzed up to month (M) 72 in 4 subpopulations: patients in remission at baseline (maintenance remitters) assigned tofacitinib 5 mg twice daily and patients not in remission at baseline (maintenance nonremitters, maintenance treatment failures, and induction nonresponders [IndNRs]) assigned tofacitinib 10 mg twice daily in OCTAVE Open. Data were analyzed overall and stratified by corticosteroid use at baseline, prior tumor necrosis factor inhibitor failure, and prior immunosuppressant failure. Among maintenance remitters and nonremitters, HRQoL outcomes were maintained up to M72: 80.0% and 100.0% of patients had an IBDQ total score ≥170, respectively. At baseline, 7.4% of maintenance treatment failures had an IBDQ total score ≥170, and this increased to 54.3% and 75.0% at M2 and M72, respectively. Corresponding values for IndNRs were 22.6%, 51.0%, and 86.0%. HRQoL outcomes were independent of treatment history. Among patients not in remission at baseline, improvement in EuroQoL-5 Dimensions Health Questionnaire and 36-Item Short Form Survey scores was maintained or achieved by M2, and steady to M72 or M33, with maintenance treatment failures and IndNR subpopulations undergoing the biggest improvements from baseline. A continued favorable impact on HRQoL was revealed with long-term tofacitinib treatment in OCTAVE Open, regardless of baseline remission status or treatment history. (ClinicalTrials.gov; number: NCT01470612).

S1023 Assessment of Health-Related Quality of Life and Patient-Reported Outcomes With Tofacitinib Treatment Stratified by Age in Patients From the OCTAVE Ulcerative Colitis Clinical Program

S1023 Assessment of Health-Related Quality of Life and Patient-Reported Outcomes With Tofacitinib Treatment Stratified by Age in Patients From the OCTAVE Ulcerative Colitis Clinical Program

S735 Mirikizumab Improves Quality of Life in Moderately-to-Severely Active UC: Improvement in IBDQ Scores in Participants of LUCENT-1 and LUCENT-2 Randomized, Double-Blind, Placebo-Controlled Phase 3 Trials

Introduction: The Inflammatory Bowel Disease Questionnaire (IBDQ) is a measure of health-related quality of life (QoL). This analysis evaluated effect of mirikizumab (miri) vs placebo (PBO) on IBDQ scores in patients (pts) with moderately-to-severely active ulcerative colitis (UC) who had failed prior conventional or biologic therapy in a Phase 3, double-blind, 12-week (W) induction study (LUCENT-1) followed by a 40W maintenance study (LUCENT-2) for a total of 52W continuous therapy. Methods: Pts (N=1162) in LUCENT-1 were randomized 3:1 to receive 300mg miri or PBO intravenously once every four weeks (Q4W). 544 pts who achieved Modified Mayo Score Clinical Response to miri by W12 of induction were rerandomized 2:1 in LUCENT-2 to subcutaneous miri 200mg or PBO Q4W in maintenance period. Randomization was stratified by previous biologic therapy failure, baseline corticosteroid use, and region. LUCENT-1 stratification included baseline (BL) disease activity, and LUCENT-2 included LUCENT-1 clinical remission status. The least squares mean change from BL in IBDQ scores at W12 of induction and W40 of maintenance was determined using analysis of covariance models. BL was W0 of therapy and stratification factors and BL scores were used as covariates. The Minimal Clinically Important Difference (MCID) was defined as an improvement of ≥16 points in total IBDQ score (IBDQ response) and IBDQ remission as a total score ≥170 points. IBDQ response and remission were calculated using non-responder imputations. Treatments were compared using the common risk difference (risk diff). Results: Miri treatment resulted in significantly greater improvement from BL in IBDQ total and domain scores vs PBO at both W12 of induction and W40 of maintenance (52W treatment) (Table). The proportions of pts who achieved an IBDQ response was significantly greater for miri treated pts vs PBO at W12 (risk diff =17.1[95%CI:10.7, 23.5]) and W40 (29.5 [21.0, 37.9]). Significantly greater proportions of pts receiving miri achieved IBDQ remission at W12 (18.1 [11.8, 24.4]) and W40 (28.5 [20.1, 37.0]) vs PBO (all evaluations and timepoints: p< 0.001). Conclusion: Pts reported significantly greater improvements in IBDQ scores at induction and maintenance with miri compared to PBO. Over 75% of pts achieved a clinically meaningful improvement in QoL, as measured by IBDQ response, at the end of the 52 weeks of miri treatment. Table 1. - LUCENT-1 and LUCENT-2 Trials Change from Baseline in the Inflammatory Bowel Disease Questionnaire IBDQ Total Score 1 IBDQ Response 2 Score Improvement ≥16 IBDQ Remission 2 IBDQ Total Score ≥170 LSM Change from BL (SE) LSM Diff (SE) n (%) Risk Diff (95% CI) n (%) Risk Diff (95% CI) LUCENT-1 Week 12 of Induction PBO IV Q4W (N=294) 25.21 (1.80) 164 (55.8) 117 (39.8) Miri 300 mg IV Q4W (N=868) 38.42 (1.11) 13.21 (2.01)* 631 (72.7) 17.1 (10.7, 23.5)* 499 (57.5) 18.1 (11.8, 24.4)* LUCENT-2 Week 40 of Maintenance (52 Weeks of Continuous Therapy) of Miri Induction Responders PBO SC (N=179) 24.51 (2.77) 88 (49.2) 77 (43.0) Miri 200 mg SC (N=365) 49.75 (2.10) 25.24 (3.09)* 289 (79.2) 29.5 (21.0, 37.9)* 264 (72.3) 28.5 (20.1, 37.0)* Abbreviations: BL=baseline; CI=confidence interval; Diff=difference; IBDQ=Inflammatory Bowel Disease Questionnaire; IV=intravenous; LSM=least squares mean; Miri=mirikizumab; n=number of patients in the specified category; N=number of patients in the analysis population; PBO=placebo; Q4W=every 4 weeks; Risk Diff=common risk difference; SC=subcutaneous; SE=standard error.1Inflammatory Bowel Disease Questionnaire domains and total scores were evaluated by analysis of covariance with modified baseline observation carried forward and adjustment for covariates.2Inflammatory Bowel Disease Questionnaire-based measurements for clinical response and remission were analyzed using non-responder imputation. The common risk difference was the stratification-adjusted difference in the proportion of participants receiving mirikizumab minus the proportion of participants receiving placebo.*p< 0.001.

P286 Sustained improvement in health-related quality of life outcomes in patients with Ulcerative Colitis with long-term tofacitinib treatment in the open-label extension study, OCTAVE Open

Abstract Background Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis (UC). Tofacitinib induction and maintenance therapy has previously been shown to improve health-related quality of life (HRQoL) outcomes. Here, we present HRQoL data from patients (pts) with UC who received tofacitinib 5 or 10 mg twice daily (BID) in the Phase 3 open-label, long-term extension (OLE) study (OCTAVE Open; NCT01470612), up to Month (M)72. Methods Proportions of pts with an Inflammatory Bowel Disease Questionnaire (IBDQ) total score ≥170, and EuroQol-5D (EQ-5D) and Short Form-36 Health Survey (SF-36) scores were analysed up to M72 in 4 subpopulations in the OLE study: ‘maintenance remitters’ completed OCTAVE Sustain in remission and received tofacitinib 5 mg BID in the OLE study; in contrast, ‘maintenance treatment failures’ (induction responders who experienced treatment failure), ‘maintenance non-remitters’ and ‘induction non-responders (IndNR)’ received tofacitinib 10 mg BID in the OLE study (Figure 1). Data were analysed for each subpopulation overall and stratified by prior tumour necrosis factor inhibitor (TNFi) failure, prior immunosuppressant failure and baseline corticosteroid use. Results Baseline demographics and clinical characteristics for each subpopulation are shown in Table 1. Among the 163 maintenance remitters, HRQoL outcomes were maintained up to M72: 80.0% of pts had an IBDQ total score ≥170 (Figure 1); changes from baseline in EQ-5D scores up to M72 and SF-36 scores up to M33 were minimal (eg M72 EQ-5D utility score -0.07 [standard deviation 0.10]; M33 SF-36 physical functioning score -1.3 [8.3]). Among pts continuing long-term tofacitinib treatment, improvement in IBDQ total score was maintained/achieved by M2 (first post-baseline assessment), and was stable up to M72, with maintenance treatment failures and IndNR subpopulations experiencing the largest improvements from baseline (Figure 1). Similar trends were observed for improvement in EQ-5D and SF-36 scores. Improvements in HRQoL outcomes were independent of prior TNFi failure, prior immunosuppressant failure or baseline corticosteroid use, eg in maintenance remitters with prior TNFi failure, 90.9% of pts had IBDQ total score ≥170 at M60 vs 88.9% of pts without prior TNFi failure. Conclusion Sustained beneficial effects in HRQoL were observed among pts continuing long-term tofacitinib treatment in OCTAVE Open. In maintenance remitters, improvements in all HRQoL outcomes were maintained with tofacitinib therapy. In pts who entered the OLE study not in remission and received tofacitinib 10 mg BID, HRQoL improvements were observed within the first 2 months, and were maintained up to M72, regardless of treatment history including prior TNFi failure.

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

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.

DOP88 Effect of risankizumab on patient-reported outcomes in patients with Crohn’s Disease who had an inadequate response or intolerance to conventional and/or biologic treatments: Results from phase 3 MOTIVATE and ADVANCE trials

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&amp;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&amp;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&amp;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.

Quality of Life and Work Productivity Improvements with Upadacitinib: Phase 2b Evidence from Patients with Moderate to Severe Crohn's Disease.

IntroductionIn the phase 2 CELEST study, positive efficacy results were obtained with the Janus kinase 1 inhibitor upadacitinib for adult patients with moderate to severe Crohn’s disease. We present the health-related quality of life and work productivity improvement results with upadacitinib from CELEST.MethodsCELEST (NCT02365649) was a double-blind study where patients were randomized 1:1:1:1:1:1 in the 16-week induction period to placebo or upadacitinib 3 mg twice daily (BID), 6 mg BID, 12 mg BID, 24 mg BID, or 24 mg once daily (QD). Patients completing the induction period were re-randomized 1:1:1 to receive upadacitinib 3 mg BID, 12 mg BID, or 24 mg QD for 36 weeks or 3 mg BID, 6 mg BID, or 12 mg BID (after amendment). Inflammatory Bowel Disease Questionnaire (IBDQ), European Quality of Life-5 Dimensions visual analog scale (EQ-5D VAS), and Work Productivity and Activity Impairment (WPAI) questionnaire outcomes were assessed at baseline and Weeks 8, 16, and 52.ResultsAt Week 16, a significant percentage (P ≤ 0.05) of patients receiving upadacitinib 6-mg BID dose or higher achieved IBDQ response (IBDQ score change ≥ 16 points; 49%–57% for upadacitinib vs. 24% for placebo) and IBDQ remission, except 24 mg QD (IBDQ score ≥ 170; 26%–39% for upadacitinib vs. 11% for placebo). Greater improvements in IBDQ total score, EQ-5D VAS, and activity impairment from baseline (P ≤ 0.1) versus placebo were also observed. Larger improvements (P ≤ 0.1) in IBDQ response and total score and EQ-5D VAS were observed at Week 8 with 6 and 24 mg BID versus placebo, with improvements for all dosages maintained or greater at Week 52 for IBDQ, EQ-5D VAS, and WPAI endpoints, in particular for the 12-mg BID group.ConclusionImprovements in health-related quality of life and work productivity were achieved and sustained with upadacitinib in patients with moderate to severe Crohn’s disease.Trial RegistrationClinicalTrials.gov identifier, NCT02365649.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-021-01660-7.

S0682 Absence of Bowel Urgency Is Associated With Significantly Improved Inflammatory Bowel Disease Related Quality of Life in a Phase 2 Trial of Mirikizumab in Patients With Ulcerative Colitis

INTRODUCTION: Mirikizumab (miri), a humanized monoclonal antibody directed against the p19 subunit of IL-23, demonstrated efficacy and was well-tolerated in a phase 2 randomized clinical trial in patients with ulcerative colitis (UC). Bowel urgency is one of the most bothersome symptoms experienced by patients with UC and is closely tied to health-related quality of life (QoL). Here we show the relationship between patient-reported urgency and Inflammatory Bowel Disease Questionnaire (IBDQ) scores. METHODS: Patients (N = 247) were randomized 1:1:1:1 to receive intravenous placebo, miri 50 mg or 200 mg with possibility of exposure-based dose increases, or fixed miri 600 mg every 4 weeks. Patients who achieved clinical response at Week 12 (decrease in 9-point Mayo score ≥2 points and ≥35% from baseline [BL], and either a decrease in rectal bleeding [RB] subscore ≥1 or RB subscore of 0 or 1; n = 106) were re-randomized 1:1 to double-blind maintenance treatment with miri 200 mg subcutaneously every 4 or 12 weeks and were treated through Week 52. Absence of urgency at Weeks 12 and 52 was defined as having no urgency for the three consecutive days prior to each scheduled visit, regardless of urgency status at BL. Patients lacking urgency data were imputed as having experienced urgency at that visit. The mean change from BL (Week 0) in IBDQ scores between patients with absence or presence of urgency at Weeks 12 and 52 was determined using analysis of covariance models. RESULTS: As previously reported, miri significantly reduced urgency over 52 weeks of treatment (1). In this analysis, total IBDQ score was significantly higher in patients with absence of urgency compared to those with presence of urgency at weeks 12 and 52. [LSM (SE)]: Week 12, 179.2 (3.6) absence, 150.5 (3.2) presence, P < 0.0001; Week 52, 186.0 (3.91) absence, 163.1 (4.35) presence, P < 0.0001. A similar pattern was observed for the 4 IBDQ subscores and corresponded to percent changes from BL (% ΔBL) that were more than two times greater in patients with absence of urgency compared to patients with presence of urgency (Table 1). CONCLUSION: In patients with absence of urgency at Weeks 12 and 52, Qol as measured by IBDQ was significantly improved compared to those with urgency. Our data demonstrate the significant negative impact of urgency on QoL in patients with UC.Table 1

DOP24 Patient-reported health-related quality-of-life outcomes with vedolizumab vs. adalimumab treatment of ulcerative colitis: Results of the VARSITY trial

Abstract Background Patients with ulcerative colitis (UC) experience substantial impairment in quality of life (QOL). Patient QOL endpoints are important measures of treatment outcome. We evaluated the effects of intravenous vedolizumab vs. adalimumab on QOL in VARSITY, the first head-to-head trial comparing the efficacy and safety of biologics in patients with moderately to severely active UC. Methods VARSITY was a phase 3b, double-blind, double-dummy, randomised trial (NCT02497469; EudraCT 2015-000939-33). QOL was assessed using the inflammatory bowel disease questionnaire (IBDQ) at baseline, Week (Week) 30, and Week 52. Endpoints included clinically meaningful IBDQ improvement (defined as an increase in total score of ≥16 points from baseline to Week 52), IBDQ remission (defined as a total score of &amp;gt;170 points at Week 52) and change from baseline in IBDQ-specific domain scores (bowel symptoms, systemic symptoms, emotional function, and social function) at Week 30 and Week 52. Serum C-reactive protein (CRP) and faecal calprotectin (FCP) were also assessed as indicators of disease activity. Results Among randomised patients, 383 (vedolizumab) and 386 (adalimumab) patients received ≥1 dose of study drug (N=769). At Week 52, clinically meaningful IBDQ improvement was observed in 52.0% (vedolizumab) vs. 42.2% (adalimumab) of patients (treatment difference 9.7%; 95% confidence interval [CI], 2.7% to 16.7%), while IBDQ remission was achieved by 50.1% (vedolizumab) vs. 40.4% (adalimumab) of patients (treatment difference 9.6%; 95% CI, 2.8% to 16.5%). Mean (standard deviation [SD]) changes in IBDQ total score from baseline for observed cases favoured vedolizumab over adalimumab (Week 30: 61.3 [39.8] vs. 52.6 [42.8]; Week 52: 66.1 [41.8] vs. 60.4 [42.2]; Figure 1). IBDQ subscores showed similar favourable trends for vedolizumab (Figure 2). At Week 52, mean (SD) changes from baseline in CRP for patients treated with vedolizumab vs. adalimumab were –50.9 (174.8) nmol/l vs. –37.2 (169.2) nmol/l and for FCP were –2187.3 (7440.4) µg/g vs. –1846.6 (4560.6) µg/g (Figure 3). Among patients with FCP &amp;gt;250 µg/g at baseline, the proportion of patients achieving FCP ≤250 µg/g was 33.9% vs. 24.5% at Week 30 and 35.2% vs. 28.9% at Week 52 for patients treated with vedolizumab vs. adalimumab, respectively. Conclusion Based on IBDQ total score and subscores, more patients with UC treated with vedolizumab than with adalimumab achieved clinically meaningful improvement and clinical remission. Reduced inflammation, as indicated by improvements in CRP and FCP, was consistent with improvements in QOL.

2913 Health-Related Quality of Life in Patients With Inflammatory Bowel Disease at the University Hospital of the West Indies

INTRODUCTION: Inflammatory bowel disease (IBD) is a chronic condition that can significantly affect health-related quality of life (HRQoL). The aim of this study is to determine the HRQoL of patients with IBD seen at the Gastroenterology clinic at the University Hospital of the West Indies (UHWI). METHODS: A cross sectional study was conducted, which included seventy patients with IBD (CD 25, UC 44 and one patient with Indeterminate colitis). Data analyses were restricted to 69 patients who had CD or UC. All the patients completed the validated Inflammatory Bowel Disease Questionnaire (IBDQ) and a questionnaire with demographic data. Disease activity was measured using Crohn's Disease Activity Index (CDAI) for CD and Truelove and Witts severity index for UC. Data analysis was conducted using Stata 14 statistical software. RESULTS: Mean age was 44.3 ± 16.2 years, 56.5% females, mean disease duration 12.0 ± 11.0 years and mean age at diagnosis of IBD was 31.5 ± 13.4 years. Patients with CD had more frequent hospital admissions (3.9 ± 3.7 vs 0.9 ± 1.8; P value 0.001) and surgeries (0.75 ± 0.8 vs 0.1 ± 0.4; P value 0.001) compared to those with UC. The mean total IBDQ score was 179.6 ± 34.4 (CD was 175.0 ± 37.1 and 182.1 ± 33.0 for patients with UC). Patients with higher IBDQ scores were more likely to be male gender (OR 1.93, 95% CI 0.69–5.39, P value 0.207), married (OR 2.25, 95% CI 0.60-7.31, P value 0.177), educated to secondary school level (OR 2.05, 95% CI 0.46-9.06, P value 0.343), employed in the private sector (OR 3.00, 95% CI 0.83-10.90, P value 0.095) and on no medications (OR 3.24, 95% CI 0.27–0.80, P value 0.006). Higher IBDQ score was associated with fewer hospital admissions (OR 0.90, 95% CI 0.73-1.10, P value 0.287). The best score was seen in the systemic domain. The lowest score was seen in emotional domain for both diseases. Overall male patients had a better score for all domains. CONCLUSION: The HRQoL for patients with IBD at the UHWI was comparable to those in other studies. Patients with UC and male gender appeared to have better quality of life, but comparisons were limited by small sample size.

Unmet Psychosocial Needs of Patients with Newly Diagnosed Ulcerative Colitis: Results from the Nationwide Prospective Cohort Study in Korea.

Background/AimsLimited data are available regarding psychosocial distress at the time of diagnosis of ulcerative colitis (UC). We investigated the psychosocial burden and factors related to poor health-related quality of life (HRQL) among patients newly diagnosed with moderate-to-severe UC who were affiliated with the nationwide prospective cohort study.MethodsWithin the first 4 weeks of UC diagnosis, all patients were assessed using the Hospital Anxiety and Depression Scale (HADS), Work Productivity and Activity Impairment questionnaire, Inflammatory Bowel Disease Questionnaire (IBDQ), and 12-Item Short Form (SF-12) health survey. A multiple linear regression model was used to identify factors associated with HRQL.ResultsBetween August 2014 and February 2017, 355 patients completed questionnaires. Significant mood disorders requiring psychological interventions, defined by a HADS score ≥11, were identified in 16.7% (anxiety) and 20.6% (depression) of patients. Patients with severe disease were more likely to have presenteeism, loss of work productivity, and activity loss than those with moderate disease (all p<0.05). Significant mood disorders had the strongest negative relationship with total IBDQ score, which indicates disease-specific HRQL (β coefficient: –22.1 for depression and –40.0 for anxiety, p<0.001). The scores of all SF-12 dimensions, which indicate general HRQL, were remarkably decreased in the study population compared indirectly with previously reported scores in the general population. The Mayo score, C-reactive protein level, and white blood cell count showed significant negative associations with the IBDQ score (p<0.05).ConclusionsPsychosocial screening and timely interventions should be incorporated into the initial care of patients newly diagnosed with UC.

P033 EFFICACY OF MIRIKIZUMAB ON HEALTH-RELATED QUALITY OF LIFE IN PATIENTS WITH ULCERATIVE COLITIS: A RANDOMISED, DOUBLE-BLIND, CONTROLLED, PHASE 2 STUDY

The efficacy and safety of mirikizumab (miri), an IL-23p19 antibody, has been evaluated in moderate-to-severe ulcerative colitis (UC) in a phase 2, randomized, double-blind, placebo (pbo)-controlled trial (AMAC, NCT02589665; presented at DDW 2018). Miri demonstrated efficacy on multiple measures in the 12-week induction treatment. This analysis evaluated the effects of miri on health-related quality of life (HRQoL) in patients with UC. Patients with moderate-to-severe UC (Mayo score 6-12; Endoscopic subscore ≥2) were randomised 1:1:1:1 to receive intravenous miri 50 mg (N=63) or 200 mg (N=62), both with possible exposure-based increase (2-12 fold or 1.5-3 fold, respectively, to a maximum 600 mg dose), or fixed dose miri 600 mg (N=61), or pbo (N=63) at Weeks 0, 4, and 8. Patients could receive oral 5-aminosalicylic acid (ASA), corticosteroids (≤20 mg/d prednisone equivalent), or thiopurines; must have failed ≥1 conventional UC therapy; and were either naïve to or had prior exposure to biologics. HRQoL was measured by the Inflammatory Bowel Disease Questionnaire (IBDQ) and evaluated using a mixed model repeated measures (MMRM) analysis. The percentage of patients at Week 12 with clinical response,1endoscopic healing,2 IBDQ total score ≥170, and IBDQ improvement ≥16 were also assessed. As early as Week 4, and continuing through Week 12, IBDQ total scores improved versus baseline and versus pbo across all miri groups except miri 50 mg versus pbo at Week 12 (Table). At Week 12, the proportions of patients with IBDQ total score ≥170 were higher with miri 50 mg, 200 mg, and 600 mg than pbo (44%, 56%, 54% vs. 30%, respectively) and higher proportions of miri- than pbo-treated patients had improvements ≥16 points from baseline in IBDQ total score. At Week 12, clinical response and endoscopic healing rates were greater for miri 50 mg and 200 mg versus pbo (Table). Induction treatment with miri was associated with HRQoL improvement in patients with UC. These are the first data evaluating the effects of an IL-23p19 antibody on the HRQoL of patients with UC.

P033 EFFICACY OF MIRIKIZUMAB ON HEALTH-RELATED QUALITY OF LIFE IN PATIENTS WITH ULCERATIVE COLITIS: A RANDOMISED, DOUBLE-BLIND, CONTROLLED, PHASE 2 STUDY

The efficacy and safety of mirikizumab (miri), an IL-23p19 antibody, has been evaluated in moderate-to-severe ulcerative colitis (UC) in a phase 2, randomized, double-blind, placebo (pbo)-controlled trial (AMAC, NCT02589665; presented at DDW 2018). Miri demonstrated efficacy on multiple measures in the 12-week induction treatment. This analysis evaluated the effects of miri on health-related quality of life (HRQoL) in patients with UC. Patients with moderate-to-severe UC (Mayo score 6-12; Endoscopic subscore ≥2) were randomised 1:1:1:1 to receive intravenous miri 50 mg (N=63) or 200 mg (N=62), both with possible exposure-based increase (2-12 fold or 1.5-3 fold, respectively, to a maximum 600 mg dose), or fixed dose miri 600 mg (N=61), or pbo (N=63) at Weeks 0, 4, and 8. Patients could receive oral 5-aminosalicylic acid (ASA), corticosteroids (≤20 mg/d prednisone equivalent), or thiopurines; must have failed ≥1 conventional UC therapy; and were either naïve to or had prior exposure to biologics. HRQoL was measured by the Inflammatory Bowel Disease Questionnaire (IBDQ) and evaluated using a mixed model repeated measures (MMRM) analysis. The percentage of patients at Week 12 with clinical response,1endoscopic healing,2 IBDQ total score ≥170, and IBDQ improvement ≥16 were also assessed. As early as Week 4, and continuing through Week 12, IBDQ total scores improved versus baseline and versus pbo across all miri groups except miri 50 mg versus pbo at Week 12 (Table). At Week 12, the proportions of patients with IBDQ total score ≥170 were higher with miri 50 mg, 200 mg, and 600 mg than pbo (44%, 56%, 54% vs. 30%, respectively) and higher proportions of miri- than pbo-treated patients had improvements ≥16 points from baseline in IBDQ total score. At Week 12, clinical response and endoscopic healing rates were greater for miri 50 mg and 200 mg versus pbo (Table). Induction treatment with miri was associated with HRQoL improvement in patients with UC. These are the first data evaluating the effects of an IL-23p19 antibody on the HRQoL of patients with UC.