Dataset Information

Association of Bowel Urgency With Quality-of-Life Measures in Patients With Moderately-to-Severely Active Ulcerative Colitis: Results From Phase 3 LUCENT-1 (Induction) and LUCENT-2 (Maintenance) Studies.

ABSTRACT:

Background

Improvement in bowel urgency (BU) was associated with better clinical outcomes in phase 3 LUCENT-1 (induction) and LUCENT-2 (maintenance) studies in moderately-to-severely active ulcerative colitis (UC). We assessed association of BU with quality-of-life (QoL) outcomes.

Methods

LUCENT-1: 1162 patients randomized 3:1 to intravenous mirikizumab 300 mg or placebo every 4 weeks (Q4W) for 12 weeks. LUCENT-2: 544 mirikizumab induction responders re-randomized 2:1 to subcutaneous mirikizumab 200 mg or placebo Q4W through Week (W) 40 (W52 of continuous treatment). Patients reported BU severity in the past 24 hours using a validated Urgency Numeric Rating Scale (NRS). In patients with baseline Urgency NRS ≥3, the association between BU Clinically Meaningful Improvement (CMI; ≥3-point decrease) and remission (score 0 or 1) with patient-reported outcomes was assessed at W12 and W52.

Results

A significantly greater proportion of patients with versus without BU Remission achieved IBDQ remission (W12: 87.3% vs 42.7%, P < .0001; W52: 91.4% vs 45.5%, p < .0001). Similarly, BU Remission was associated with more patients achieving CMI in SF-36 Physical Component Summary (W12: 69.0% vs 44.4%, P < .0001; W52: 77.5% vs 42.1%, P < .0001) and Mental Component Summary (W12: 53.5% vs 41.0%, P = .0019; W52: 62.0% vs 38.3%, P < .0001) scores. At W12 and W52, patients with BU CMI or Remission showed significant improvements in EQ-5D-5L and Work Productivity and Activity Impairment:UC scores. Significant improvements were also seen in fatigue, abdominal pain, and nocturnal stool.

Conclusions

In patients with moderately-to-severely active UC, improvement in BU was associated with improved QoL in phase 3 LUCENT-1 and LUCENT-2 studies.

Clinical studies

LUCENT-1: NCT03518086; LUCENT-2: NCT03524092.

SUBMITTER: Long MD

PROVIDER: S-EPMC10838132 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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Publications

Association of Bowel Urgency With Quality-of-Life Measures in Patients With Moderately-to-Severely Active Ulcerative Colitis: Results From Phase 3 LUCENT-1 (Induction) and LUCENT-2 (Maintenance) Studies.

Long Millie D MD Schreiber Stefan S Hibi Toshifumi T Gibble Theresa Hunter TH Fisher Deborah A DA Park Gina G Moses Richard E RE Higgins Peter D R PDR Lindsay James O JO Lee Scott D SD Escobar Rodrigo R Jairath Vipul V Jairath Vipul V

Crohn's & colitis 360 20240106 1

<h4>Background</h4>Improvement in bowel urgency (BU) was associated with better clinical outcomes in phase 3 LUCENT-1 (induction) and LUCENT-2 (maintenance) studies in moderately-to-severely active ulcerative colitis (UC). We assessed association of BU with quality-of-life (QoL) outcomes.<h4>Methods</h4>LUCENT-1: 1162 patients randomized 3:1 to intravenous mirikizumab 300 mg or placebo every 4 weeks (Q4W) for 12 weeks. LUCENT-2: 544 mirikizumab induction responders re-randomized 2:1 to subcutane ...[more]

PMID: 38313767

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Project description:BackgroundMirikizumab, an anti-IL-23p19 antibody, demonstrated efficacy in phase 3, randomized, double-blind, placebo-controlled LUCENT-1 (induction/NCT03518086) and LUCENT-2 (maintenance/NCT03524092) ulcerative colitis (UC) studies. We evaluated the effect of mirikizumab on quality-of-life (QoL) outcomes in these studies.MethodsIn LUCENT-1, 1162 patients with moderately-to-severely active UC were randomized 3:1 to receive mirikizumab 300 mg intravenous or placebo every 4 weeks (Q4W) for 12 weeks. In LUCENT-2, mirikizumab induction responders (N = 544) were re-randomized 2:1 to receive mirikizumab 200 mg subcutaneous or placebo Q4W through week (W) 40 (W52 of treatment). QoL was assessed at W12 and W52 using patient-reported outcomes. Treatments were statistically compared using analysis of covariance model (continuous outcomes) and Cochran-Mantel-Haenszel test (binary outcomes).ResultsAt W12 and W52, mirikizumab showed significant improvement in Inflammatory Bowel Disease Questionnaire (IBDQ) total and domain scores (P < .001); 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS), Mental Component Summary (MCS), and domain scores (P < .05); EQ-5D-5L scores (P < .001); Work Productivity and Activity Impairment Questionnaire (UC) scores (P < .05); Patient Global Rating of Severity (P < .001); and Patient Global Rating of Change (P < .01) scores. A significantly higher proportion of mirikizumab-treated patients achieved IBDQ response (W12: 72.7% vs 55.8%; W52: 79.2% vs 49.2%; P < .001), IBDQ remission (W12: 57.5% vs 39.8%; W52: 72.3% vs 43.0%; P < .001), and clinically important improvements in PCS (W12: 50.6% vs 41.5%; W52: 61.9% vs 36.9%; P < .01) and MCS (W12: 44.2% vs 37.8%; W52: 51.2% vs 34.6%; P < .05) scores.ConclusionsMirikizumab improved QoL in patients with moderately-to-severely active UC in phase 3 LUCENT-1 and LUCENT-2 studies.Clinical trials registration numberLUCENT-1: NCT03518086; LUCENT-2: NCT03524092.

Project description:BackgroundDue to wide-ranging impacts of Ulcerative Colitis (UC), regulatory authorities emphasize the importance of including validated patient-reported symptom severity measures in clinical trials.AimTo describe the development and validation of the Ulcerative Colitis-Symptom Questionnaire (UC-SQ).MethodsThe UC-SQ was developed in a qualitative study involving a targeted literature review, semi-structured concept elicitation interviews, and combined concept elicitation/cognitive interviews. Measurement properties, including item-level analyses, factor structure, reliability, validity, responsiveness, and clinically meaningful change were evaluated using data from a phase 2b, randomized trial in adults with UC (N = 113).ResultsFourteen symptom concepts were elicited across 22 interviews, with saturation at the fifth interview. Twenty-two items were unmodified as cognitive interview participants interpreted underlying concepts correctly. Instructions were clear and items were relevant, with appropriate response options and recall periods. Reduction to 17 items was completed prior to psychometric testing. Two items (joint pain/constipation) did not contribute to reliability in initial testing and were included as non-scored items. The 15-item UC-SQ showed evidence of internal consistency (α = 0.86) and test-retest reliability (intraclass correlation coefficient = 0.88). The UC-SQ discriminated by disease severity as defined by Mayo and Inflammatory Bowel Disease Questionnaire scores (p < 0.0001). Convergent validity was supported by strong correlations with criterion measures. The UC-SQ was responsive in patients indicating change in other measures. A 10-point decrease from baseline indicated within-patient meaningful improvement.ConclusionsThe UC-SQ is reliable, valid and responsive, with a 10-point improvement estimating within-patient clinically meaningful improvement. The tool is fit-for-purpose as a key endpoint in pivotal UC trials.

Project description:BackgroundWe evaluated the health-related quality of life (HRQoL) benefits of upadacitinib (UPA) induction and maintenance treatment in a phase 3 study of patients with ulcerative colitis (UC) across a broad range of patient-centered outcomes.MethodsPatients received UPA 45 mg once daily or placebo as induction treatment for 8 weeks. Patients who achieved clinical response were rerandomized to receive once daily UPA 15 mg, 30 mg, or placebo as maintenance treatment for 52 weeks. The percentages of patients reporting a clinically meaningful within-person change from baseline in the Ulcerative Colitis Symptoms Questionnaire, Inflammatory Bowel Disease Questionnaire, Work Productivity and Impairment Questionnaire, 36-Item Short Form Survey, and European Quality of Life-5 Dimension 5 Levels were evaluated at weeks 2 and 8 of induction and at weeks 0 and 52 of maintenance.ResultsSignificant improvements from baseline in all HRQoL measures except the Work Productivity and Impairment Questionnaire-absenteeism were achieved with UPA (P < .001) vs placebo as early as week 2 of induction. These improvements were sustained at week 52 with significantly more patients treated with either 15 mg or 30 mg UPA vs placebo achieving meaningful within-person change in the Ulcerative Colitis Symptoms Questionnaire; Inflammatory Bowel Disease Questionnaire; overall work impairment, presenteeism, and activity impairment; both 36-Item Short Form Survey Physical and Mental Component Summaries; and European Quality of Life-5 Dimension 5 Levels (P < .001).ConclusionsInduction treatment with UPA 45 mg significantly improved HRQoL measures. A significantly higher percentage of patients who responded to induction treatment with UPA maintained clinically meaningful improvements consistently across a wide range of HRQoL outcomes after 52 weeks of maintenance therapy with UPA (15 mg and 30 mg) compared with placebo. (ClinicalTrials.gov, Numbers: NCT02819635, NCT03653026).

Project description:Background and aimsTo assess golimumab pharmacokinetics [PK] and exposure-response [ER] in adults with moderate-to-severe ulcerative colitis [UC] from the Program of Ulcerative Colitis Research Studies Utilizing an Investigational Treatment [PURSUIT] studies.MethodsWe analysed golimumab PK and ER data of patients with moderate-to-severe UC from the PURSUIT-subcutaneous induction [N = 1064] and maintenance [N = 464] studies. Induction analyses evaluated serum golimumab concentration [SGC] and efficacy data through Week [wk] 6 following subcutaneous doses at wk0 and wk2; maintenance analyses assessed data through wk54 following 4-weekly dosing. ER relationships were assessed using trend, logistic regression, and receiver-operating-characteristic curve analyses.ResultsMedian SGCs peaked at induction wk2 for golimumab 100/50mg, 200/100mg, and 400/200mg. Wk6 median SGCs were 0.78, 1.78, and 4.01 μg/ml, respectively. SGCs were sustained, reaching steady state approximately 8wks after golimumab maintenance commenced [wk14 of golimumab] regardless of induction dose. Median trough SGCs from maintenance wks8-44 ranged from 0.69 to 0.83 µg/ml [50 mg] and 1.33-1.58 µg/ml [100 mg]. SGCs were approximately dose proportional, and higher SGCs were associated with higher efficacy response rates during induction and maintenance. Factors associated with golimumab exposure were body weight, antibody-to-golimumab status, serum albumin, alkaline phosphatase, faecal markers, C-reactive protein, and pancolitis. SGCs of 2.5 µg/ml [induction wk6] and 1.4 µg/ml [maintenance steady-state trough] are potential target concentrations. Immunomodulators had no apparent impact on SGC with golimumab 100mg, whereas drug levels were slightly higher with golimumab 50mg with vs without immunomodulators.ConclusionsSGCs are approximately dose proportional, and a positive SGC-efficacy relationship exists during induction/maintenance golimumab treatment of adult UC patients. Optimal SGC targets require validation in prospective studies.

Dataset Information

Association of Bowel Urgency With Quality-of-Life Measures in Patients With Moderately-to-Severely Active Ulcerative Colitis: Results From Phase 3 LUCENT-1 (Induction) and LUCENT-2 (Maintenance) Studies.

Background

Methods

Results

Conclusions

Clinical studies

Publications

Association of Bowel Urgency With Quality-of-Life Measures in Patients With Moderately-to-Severely Active Ulcerative Colitis: Results From Phase 3 LUCENT-1 (Induction) and LUCENT-2 (Maintenance) Studies.

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