Introduction
Bowel urgency (BU), the sudden or immediate need to have a bowel movement, is an impactful symptom of Crohn’s disease (CD) that varies in intensity1. We report the efficacy of the IL-23 p19 inhibitor, mirikizumab (miri) in improving BU among patients with moderately-to-severely active CD from the phase 3 VIVID-1 trial (NCT03926130). VIVID-1 co-primary and gated endpoints, including comparison with ustekinumab, are already reported2.
Aims & Methods
Adult patients (N=1065) were randomised to placebo (PBO) or miri 900mg intravenously at weeks (W) 0, 4, and 8, then 300mg subcutaneously every 4 weeks (Q4W) from W12 to W52. At W12, PBO responders continued PBO to W52, non-responders received the blinded miri regimen per protocol. BU was assessed at W12 and W52 using the Urgency Numeric Rating Scale (UNRS)3. We evaluated the proportion of patients with baseline (BL) UNRS ≥3 and ≥6 who achieved BU Clinically Meaningful Improvement (CMI; >3 change in UNRS) and BU remission (UNRS ≤2). Treatment comparisons used Cochran-Mantel-Haenszel tests with non-responder imputation for missing values.
Results
Study population: 55.1% male. Mean (SD) age 36.2 (13.0) years. Disease duration 7.4 (7.9) years. At BL, median (Q1, Q3) UNRS 6.9 (5.2, 8.1), 94.5% patients achieved UNRS ≥3 and 66.0% patients achieved ≥6. In patients with BL UNRS ≥3, nominally significantly higher proportions of miri versus PBO patients achieved BU CMI and BU remission at both W12 and W52 (Table). A nominally significantly greater proportion of miri-treated patients achieved W52 BU CMI-composite and BU remission-composite (Table). Similar results were seen with BL UNRS ≥6.
|
| W12 PBO | W12 Miri | W12 p-value | W12 95% CI | W52 PBO | W52 Miri | W52 p-value | W52 95% CI |
| UNRSa CFB (LSM ±SE) | -1.58 (0.168) | -2.44 (0.099) | 0.00011 | -1.24, -0.48 | -1.23 (0.180) | -3.24 (0.106) | <0.0001 | -2.42, -1.60 |
Patients with BL UNRS ≥3 | BU CMI-TT | 50/186 (26.9) | 227/547 (41.5) | 0.0004 | 6.7, 22.0 | 38/186 (20.4) | 301/547 (55.0) | <0.0001 | 28.0, 42.1 |
| BU CMI-compositeb |
| 38/186 (20.4) | 251/547 (45.9) | <0.0001 | 18.5, 32.8 |
| BU Remissionc-TT | 29/186 (15.6) | 134/547 (24.5) | 0.01 | 2.3, 15.0 | 21/186 (11.3) | 209/547 (38.2) | <0.0001 | 21.0, 33.2 |
| BU Remission-composite |
| 21/186 (11.3) | 180/547 (32.9) | <0.0001 | 15.7, 27.8 |
Patients with BL UNRS ≥6 | BU CMI-TT | 38/137 (27.7) | 180/376 (47.9) | 0.0001 | 9.8, 28.2 | 31/137 (22.6) | 229/376 (60.9) | <0.0001 | 30.1, 47.3 |
| BU CMI-composite |
| 31/137 (22.6) | 188/376 (50.0) | <0.0001 | 18.4, 36.0 |
| BU Remission-TT | 11/137 (8.0) | 70/376 (18.6) | 0.007 | 3.8, 15.8 | 13/137 (9.5) | 126/376 (33.5) | <0.0001 | 17.1, 31.1 |
| BU Remission-composite |
| 13/137 (9.5) | 111/376 (29.5) | 0.0002 | 13.2, 27.0 |
PBO, N=199; Miri, N=579. Data are N (%) unless otherwise stated.
aUNRS scale: 0 (no urgency)-10 (worst possible urgency)
3.
bComposite=Clinical response by PRO (2 of the patient-reported items of the CDAI, AP and SF) at W12 and W52 parameter (CMI or Remission).
cBU remission=no to minimal BU (UNRS≤2). Treatment comparison: CFB used a mixed model for repeated measures model containing treatment, BL value, visit, stratification factors and interaction of BL value by visit and treatment by visit. Response rates used
Cochran-Mantel-Haenszel tests with non-responder imputation. AP=abdominal pain; BL=baseline; CFB=change from BL; CI=confidence interval; CMI=clinically meaningful improvement; LSM=least squares mean; PBO=placebo; PRO=Patient Reported Outcome; SD=standard deviation; SE=standard error; SF=stool frequency; TT=treat-through; UNRS=Urgency Numeric Rating Scale; W=week.
Conclusion
BU is one of the most unrecognised symptoms in patients with CD. Patients enrolled in VIVID-1 had high BU scores at BL. Compared to PBO-treated pts, miri-treated pts achieved nominally significantly higher rates of BU CMI and remission at W12 and W52.
References
1. Dulai PS, et al. Aliment Pharmacol Ther 2020; 51(11): 1047-66.
2. Ferrante, M et al. (2024). Journal of Crohn's and Colitis, 18(Supplement_1), i7-i9.
3. Dubinsky MC, et al.. Qual Life Res 2023; 32(12): 3403-15.
Disclosure
VP consulting/advisory board fees from AbbVie, Alimentiv Inc., Arena pharmaceuticals, Asahi Kasei Pharma, Asieris, Astra Zeneca, Avoro Capital, Bristol Myers Squibb, Celltrion, Lilly, Endpoint Health, Enthera, Ferring, Flagship Pioneering, Fresenius Kabi, Galapagos, Gilde Healthcare, GlaxoSmithKline, Genentech, Gilead, Innomar, JAMP, Janssen, Merck, Metacrine, Mylan, Pandion, Pendopharm, Pfizer, Protagonist, Prometheus Biosciences, Reistone Biopharma, Roche, Roivant, Sandoz, SCOPE, Second Genome, Sorriso, Takeda, TD Securities, Teva, Topivert, Ventyx, and Vividion; speaker’s fees from, Abbvie, Ferring, Bristol Myers Squibb, Galapagos, Janssen Pfizer Shire, Takeda, and Fresenius Kabi.
BES consulting fees from Abbvie, Alimentiv, Amgen, Arena Pharmaceuticals, Artugen Therapeutics, Astra Zeneca, Boehringer IngelheSim, Boston Pharmaceuticals, Calibr, Celgene, Celltrion, ClostraBio, Equillium, Enthera, Evommune, Fresenius Kabi, Galapagos, Genentech (Roche), Gilead Sciences, GlaxoSmithKline, Gossamer Bio, Index Pharmaceuticals, Innovation Pharmaceuticals, Inotrem, Kaleido, Kallyope, Merck, Morphic Therapeutics, MRM Health, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonist Therapeutics, Q32 Bio, Sun Pharma, Surrozen, Target RWE,Teva, TLL Pharmaceutical, and Ventyx Biosciences; consulting/speaking fees from Abivax; consulting/speaking fees/other support from Lilly, Bristol Myers Squibb, Janssen, Pfizer, and Takeda; research grants and consulting fees from Theravance Biopharma; stock options from Ventyx Biopharma.
MC speaker, consultant, or has received research/education funding from MSD, AbbVie, Hospira, Pfizer, Takeda, Janssen, Ferring, Shire Pharmaceuticals, Dr Falk Pharma, Tillotts Pharma, Biogen, Gilead, and Lilly.
MChen provided educational activities for AbbVie, China Medical System, IPSEN, Janssen, and Takeda; advisory board for Boehringer Ingelheim and Janssen; support for clinical research from Janssen and Takeda.
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ST consultancy from Biogen, Bristol-Myers Squibb, Celgene, ChemoCentryx, Cosmo, Enterome, Ferring, Giuliani, GlaxoSmithKline, Genentech, Immunocore, Immunometabolism, Janssen, Lilly, MSD, Merck, Neovacks, Novonordisk, Novartis, NPS Pharmaceuticals, Pfizer, Proximagen, Receptos, Roche, Shire, Sigmoid Pharma, Takeda, Topivert, UCB, VHsquared, Vifor, Zeria, Sensyne, Satisfai, Bioclinica, Equillium, Mestag, Sorriso, Protagonist; research support from AbbVie, the International Organization for the Study of Inflammatory Bowel Diseases, Lilly, UCB, Vifor, Norman Collisson Foundation, Pfizer, UK–India Education and Research Initiative, ECCO Health Care, the Helmsley Trust; honoraria from AbbVie, Amgen, Biogen, Ferring, Takeda, Lilly; travel expenses covered or reimbursed from AbbVie, Lilly, Johnson & Johnson, Pfizer, Takeda, Ferring, Amgen, and Biogen.
HC, ZL, RM, MP, AV and KT are employees and stockholders of Lilly.
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