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Clinical Trial
. 2025 Jul 1;9(1):75.
doi: 10.1186/s41687-025-00906-0.

Bowel urgency in ulcerative colitis: effect of baseline urgency and change in urgency in response to mirikizumab

David B Clemow  1 , Marla C Dubinsky  2 , Simin K Baygani  3 , Bruce E Sands  4 , Anthony Keohane  5 , Silvio Danese  6 , Stefan Schreiber  7 , Alissa J Walsh  8 , Toshifumi Hibi  9 , Theresa Hunter Gibble  3 , Richard E Moses  3 , Simon P L Travis  10
Affiliations
Clinical Trial

Bowel urgency in ulcerative colitis: effect of baseline urgency and change in urgency in response to mirikizumab

David B Clemow et al. J Patient Rep Outcomes. .

Abstract
in English, German

Background: Mirikizumab has demonstrated efficacy in moderately to severely active ulcerative colitis. A 1-2-point change in Urgency Numeric Rating Scale (NRS) score can be meaningful for patients. In these post-hoc analyses, we evaluated the efficacy of mirikizumab compared to placebo by baseline Urgency NRS score groups (0-3, 4-6, and 7-10) and its effect on bowel urgency severity over time.

Methodology: Urgency NRS was measured as a secondary outcome at baseline, week 12, and week 52. Bowel urgency improvement was assessed for patients who achieved and did not achieve multiple efficacy endpoints. Data were analyzed using Fisher's exact test with nonresponder imputation.

Results: At weeks 12 and 52, a significantly higher percentage of mirikizumab-treated patients achieved clinical response as well as clinical, endoscopic, and symptomatic remission compared to placebo-treated patients, regardless of baseline Urgency NRS score category (higher proportions versus placebo, delta 9%-45%). Improvement in Urgency NRS score category at weeks 12 and 52 for mirikizumab-treated patients was observed when other efficacy outcomes were achieved (13%-90%) and not achieved (12%-75%).

Conclusions: A greater proportion of mirikizumab-treated patients with ulcerative colitis achieved symptomatic, clinical, and endoscopic remission endpoints compared to placebo-treated patients, regardless of baseline bowel urgency severity. After one year, bowel urgency was improved to a greater extent with mirikizumab than with placebo, even for patients who did not achieve other clinical outcomes. Small improvements in bowel urgency are associated with significant health-related quality-of-life improvements. Monitoring shifts in urgency severity over time using the Urgency NRS can aid in understanding patients' treatment outcomes.

Trial registration: LUCENT-1 (NCT03518086) Registered 04 May 2018 https://clinicaltrials.gov/study/NCT03518086 . LUCENT-2 (NCT03524092) Registered 10 May 2018 https://clinicaltrials.gov/study/NCT03524092 .

For patients with ulcerative colitis and different levels of bowel urgency severity at baseline, mirikizumab improved bowel urgency more than placebo, even for those who did not achieve full clinical benefit. Small improvements in bowel urgency are associated with significant health-related quality of life improvements, so assessing bowel urgency improvements over time aids in understanding patients’ treatment outcomes.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: Informed consent was obtained from all participants included in these studies. This study was performed in compliance with the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use Good Clinical Practice guidelines. Approval was granted by the ethics board that reviewed the study at each site level for each study (LUCENT-1 (NCT03518086); LUCENT-2 (NCT03524092)). Consent for publication: Not applicable. Competing interests: D.B.C., SK.B., T.H.G., and R.E.M. are employees and stockholders of Eli Lilly and Company. M.C.D. reports consulting fees from AbbVie, Arena Pharmaceuticals, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly and Company, F. Hoffmann-La Roche, Genentech (Roche), Gilead Sciences, Janssen, Pfizer, Prometheus Biosciences, Takeda, and UCB; contracted research from AbbVie and Janssen; stock interest in Trellus Health; and licensing fees from Takeda. B.E.S. reports consulting fees from AbbVie, Alimentiv, Amgen, Arena Pharmaceuticals, Artugen Therapeutics, AstraZeneca, Biora Therapeutics, Inc., Boehringer Ingelheim, Boston Pharmaceuticals, Calibr, Celgene, Celltrion, ClostraBio, Enthera, Equillium, Evommune, Fresenius Kabi, Galapagos, Genentech (Roche), Gilead Sciences, GlaxoSmithKline, Gossamer Bio, Index Pharmaceuticals, Innovation Pharmaceuticals, Inotrem, Kaleido Biosciences, Kallyope, Merck & Co., Morphic Therapeutic, MRM Health, Prometheus Biosciences, Prometheus Laboratories, Protagonist Therapeutics, Q32 Bio, Sun Pharma, Surrozen, Target RWE, Teva Pharmaceuticals, TLL Pharmaceuticals LLC, and Ventyx Biosciences; consulting and speaking fees from Abivax; consulting and speaking fees and other support from Eli Lilly and Company; research grants, consulting and speaking fees, and other support from Bristol Myers Squibb, Janssen, Pfizer, and Takeda; research grants and consulting fees from Theravance Biopharma; and stock options from Ventyx Biosciences. A.K. is an employee of HaaPACS GmbH, Statistics, Germany, and reports being a contractor for Eli Lilly and Company. S.D. reports consultancy fees from AbbVie, Alimentiv, Allergan, Amgen, AstraZeneca, Athos Therapeutics, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly and Company, Enthera, Ferring Pharmaceuticals, Gilead Sciences, Hospira, Inotrem, Janssen, Johnson & Johnson, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity Therapeutics, Takeda, TiGenix, UCB, and Vifor. S.S. reports personal fees for consulting in advisory boards from AbbVie, Amgen, Arena Pharmaceuticals, Biogen, Bristol Myers Squibb, Celgene, Celltrion, Dr. Falk Pharma, Eli Lilly and Company, Ferring, Fresenius, Galapagos, Gilead Sciences, I-Mab, Janssen, MSD, Mylan, Pfizer, Protagonist Therapeutics, Provention Bio, Sandoz/Hexal, Takeda, Theravance Biopharma, and UCB. A.J.W. reports personal fees from AbbVie, Alfasigma, Bristol Myers Squibb, Dr. Falk Pharma, Eli Lilly and Company, Ferring, Galapagos, GlaxoSmithKline, Janssen, Pfizer, Sandoz, and Takeda. T.H. reports lecture fees from AbbVie, Ferring, Gilead Sciences, Janssen, JIMRO, Kissei Pharmaceutical, Kyorin Pharmaceutical, Mitsubishi Tanabe Pharma, Miyarisan Pharmaceutical, Mochida Pharmaceutical, Nippon Kayaku, Takeda, and Zeria Pharmaceutical; advisory/consultancy fees from EA Pharma, Eli Lilly and Company, Janssen, Mitsubishi Tanabe Pharma, Pfizer, Takeda, and Zeria Pharmaceutical; and research grants from AbbVie, JIMRO, and Zeria Pharmaceutical. S.P.L.T. reports grants/research support from AbbVie, Buhlmann, Celgene, Eli Lilly and Company, IOIBD, Janssen, Norman Collisson Foundation, Pfizer, Takeda, UCB, and Vifor; consulting fees from Abacus Pharma, AbbVie, Actial, ai4gi, Alcimed, Allergan, Amgen, Aptel, Arena Pharmaceuticals, Asahi Kasei Pharma Corporation, Aspen Pharmacare, Astellas Pharma, AstraZeneca, Atlantic Pharma, Barco, Biocare, Biogen, BL Pharma, Boehringer Ingelheim, Bristol Myers Squibb, Buhlmann, Calico, Celgene, Cellerix, Cerimon Pharmaceuticals, ChemoCentryx, Chiesi, Cisbio, Comcast, Coronado Biosciences, Cosmo, Ducentis BioTherapeutics, Dr. Falk Pharma, Dynavax Technologies, Elan Pharmaceuticals, Eli Lilly and Company, Enterome, Ferring, FPRT Bio, Galapagos, Genentech/Roche, Genzyme, Gilead Sciences, GlaxoSmithKline, Glenmark Pharmaceuticals, Grünenthal, GW Pharmaceuticals, Immunocore, Indigo, Janssen, Lexicon Pharmaceuticals, Medarex, Medtrix, Merck, Merrimack Pharmaceuticals, Millenium Pharmaceuticals, Neovacs, Novartis, Novo Nordisk, NPS Pharmaceuticals/Nycomed, Ocera Therapeutics, Optima Pharma, Origin, Otsuka Pharmaceutical, Palau Pharma, Pentax Medical, Pfizer, PharmaVentures, Philips, Procter & Gamble, Pronota, Proximagen, Resolute Therapeutics, Robarts, Sandoz, Santarus, Satisfai Health, Sensyne Health, Shire, Sigmoid Pharma, Souffinez, Sun Pharma, SynDermix, Synthon, Takeda, Theravance Biopharma, TiGenix, Tillotts, TopiVert Pharma, Trino Therapeutics with Wellcome Trust, TxCell, UCB, Vertex Pharmaceuticals, VHsquared, Vifor, Warner Chilcott, and Zeria Pharmaceutical; and speaker fees from AbbVie, Amgen, Biogen, Dr. Falk Pharma, Ferring, Janssen, Pfizer, Shire, Takeda, and UCB.

Figures

Fig. 1
Fig. 1
Clinical response, clinical remission, or endoscopic remission at weeks 12 and 52. Using NRI, data are shown as the percentage (95% CI) of patients in the modified intention-to-treat population meeting the criteria for clinical response at (A) week 12 and (B) week 52, clinical remission at (C) week 12 and (D) week 52, or endoscopic remission at (E) week 12 and (F) week 52, for patients who received (A, C, E) mirikizumab versus placebo or (B, D, F) mirikizumab versus mirikizumab-to-placebo by Urgency NRS score at induction baseline. *P < 0.05; **P < 0.01; ***P < 0.001 vs PBO. Week 12: PBO, N = 294; MIRI, N = 868. Week 52: PBO, N = 179; MIRI, N = 365. See the Efficacy Endpoints section for definitions. Abbreviations: CI, confidence interval; IV, intravenous; MIRI, mirikizumab; N, number of patients in the analysis population or the number of patients in each Urgency NRS score grouping; n, number of patients within analyzed group achieving the endpoint of interest; NRI, nonresponder imputation; NRS, Numeric Rating Scale; ns, not significant; SC, subcutaneous; UNRS, Urgency Numeric Rating Scale
Fig. 2
Fig. 2
(A, B) Symptomatic remission, (C, D) BU remission, or (E, F) IBDQ remission at weeks 12 and 52. Using NRI, data are shown as the percentage (95% CI) of patients in the modified intention-to-treat population meeting the criteria for symptomatic remission at (A) week 12 and (B) week 52, BU remission at (C) week 12 and (D) week 52, or IBDQ remission at (E) week 12 and (F) week 52, for patients who received (A, C, E) mirikizumab versus placebo or (B, D, F) mirikizumab versus mirikizumab-to-placebo by Urgency NRS score at induction baseline. *P < 0.05; **P < 0.01; ***P < 0.001 vs PBO. Week 12: Placebo, N = 294; MIRI, N = 868. Week 52: PBO, N = 179; MIRI, N = 365. See the Efficacy Endpoints section for definitions. The number of patients for BU remission is lower because this endpoint was only calculated for patients with an Urgency NRS score ≥ 3 at baseline. Abbreviations: BU, bowel urgency; CI, confidence interval; IBDQ, Inflammatory Bowel Disease Questionnaire; IV, intravenous; MIRI, mirikizumab; N, number of patients in the analysis population OR the number of patients in each Urgency NRS score grouping; n, number of patients within analyzed group achieving the endpoint of interest; na, not applicable (due to small N); NRI, nonresponder imputation; NRS, Numeric Rating Scale; ns, not significant; SC, subcutaneous; UNRS, Urgency Numeric Rating Scale
Fig. 3
Fig. 3
Shift in Urgency NRS score group from induction baseline to weeks 12 and 52 by treatment and clinical remission status. Purple indicates improvement by 2 group levels, light purple indicates improvement by 1 group level, gray indicates no change, light orange indicates worsening by 1 level, and dark orange indicates worsening by 2 levels. Patients at week 52 were responders to mirikizumab induction therapy at week 12 who were rerandomized to mirikizumab or placebo (treatment withdrawal). Abbreviations: N, number of patients in the analysis population OR the number of patients in each Urgency NRS score grouping; n, number of patients within analyzed group achieving the endpoint of interest; NRS, Numeric Rating Scale; UNRS, Urgency Numeric Rating Scale
Fig. 4
Fig. 4
Shift in Urgency NRS score from induction baseline to week 52 by treatment and clinical remission status. Purple indicates improvement, gray indicates no change, and orange indicates worsening. An Urgency NRS score of 0 or 1 is considered bowel urgency remission and is noted with a black outline. Patients at week 52 were responders to mirikizumab induction therapy at week 12 who were rerandomized to mirikizumab or placebo (treatment withdrawal). Abbreviations: N, number of patients in the analysis population OR the number of patients in each Urgency NRS score grouping; n, number of patients within analyzed group achieving the endpoint of interest; NRS, Urgency Numeric Rating Scale; UNRS, Urgency Numeric Rating Scale
Fig. 5
Fig. 5
Clinical relevance of Urgency NRS score improvement shifts. aIBDQ data shown are based on the evaluable overall population (n = 26, 39, 49, 32, and 25 for 1, 2, 4, 6, and 8-point Urgency NRS reductions, respectively), not the n from the individual shift examples shown, with the 8-pt data based upon 8 to 10-pt reductions. bPatients with a low Urgency NRS at baseline have less of an opportunity to have a 3-point improvement
See this image and copyright information in PMC

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