Introduction
Bowel urgency (BU) is a common, debilitating symptom among patients with ulcerative colitis (UC).1 LUCENT-URGE is a Phase 3b, open-label, single-arm 28-week (W) study in adults with moderately-to-severely active UC and BU (Urgency Numeric Rating Scale [UNRS] ≥3) at baseline treated with mirikizumab (MIRI). Here, we report W28 results from LUCENT-URGE (NCT05767021).
Aims & Methods
Patients were treated with intravenous MIRI 300 mg at W0, 4 and 8, followed by 200 mg subcutaneous at W12, 16, 20, and 24. The primary objective was to assess improvement in UNRS at W12. Key secondary objectives included evaluating the improvement in UNRS at W28, the improvement in Stool Deferral Time (SDT) and Bowel Urgency Frequency (BUF) at W12 and W28, the proportion of participants achieving clinical remission and an UNRS score of ≤1 (BU remission) at W12 and W28, and the proportion of participants achieving clinical response and an improvement in UNRS score ≥3 (clinically meaningful improvement [CMI] of UNRS) at W12 and W28. UNRS and BUF was measured using a daily diary where patients recorded the number of times they experienced BU in the past 24 hours and was averaged over a 7-day period. SDT was reported in minutes (min), and the shortest weekly SDT was used. Baseline observation carried forward was used as the endpoint for the corresponding visit for all missing observations. Missing continuous data were treated as no change from baseline and binary endpoints were treated as nonresponse for participants that discontinue prior to the time point of interest.
Results
172 patients were enrolled from 8 countries. Baseline modified Mayo score (MMS; mean± standard deviation [SD]) was 6.8±1.3, and 64.0% patients had severe disease activity (MMS 7-9). Baseline mean duration of UC was 8.0 years, mean UNRS score was 6.9 and mean BUF was 6.9 times/day. Mean UNRS and BUF improved from baseline to W28 by 3.6 and 3.8, respectively. The proportion of patients with SDT defined as “≥15 min or no urgency” was 4.1% at baseline and improved to 29.7% at W28 (Table 1). At W12, 36 (20.9%) patients achieved clinical remission, 54 (31.4%) achieved endoscopic remission, and 92 (53.5%) achieved CMI of UNRS. At W28, 62 (36.1%) patients achieved clinical remission, 76 (44.2%) achieved endoscopic remission, and 100 (58.1%) achieved CMI of UNRS. 76 (44.2%) patients achieved both clinical response and CMI of UNRS at W12, and 86 (50.0%) patients at W28. At W12 and W28, 8 patients (4.7%) and 28 patients (16.3%) achieved both clinical remission and BU remission, respectively. The safety profile of MIRI observed in LUCENT-URGE was consistent with previous studies, with no death reported and similar frequency of treatment-emergent adverse events (TEAEs). Most common TEAEs were ulcerative colitis exacerbation (5.2%) and upper respiratory tract infection (5.2%).
Table 1. Change in Bowel Urgency Measures from Baseline at Week 12 and Week 28, BOCF
| BU Measures |
| Baseline | Week 12 | Week 28 |
UNRS (BU severity) scorea
[range 0-10], mean (SD) |
| 6.9 (1.6) | 3.7 (2.6) | 3.3 (2.9) |
BU Frequencyb
[times/day], mean (SD) |
| 6.9 (3.7) | 3.1 (3.0) | 3.1 (3.5) |
| SDTc, n (%) | <1 minute | 34 (19.8) | 15 (8.7) | 14 (8.1) |
| ≥1 to <2 minutes | 59 (34.3) | 37 (21.5) | 31 (18.0) |
| ≥2 to <5 minutes | 57 (33.1) | 52 (30.2) | 45 (26.2) |
| ≥5 to <15 minutes | 15 (8.7) | 41 (23.8) | 31 (18.0) |
| ≥15 minutes or no urgency | 7 (4.1) | 27 (15.7) | 51 (29.7) |
BOCF=Baseline Observation Carried Forward; BU=Bowel Urgency; CFB=Change from Baseline; IV= Intravenous; MIRI=Mirikizumab; UNRS= Urgency Numeric Rating Scale; SC= Subcutaneous; SD=Standard Deviation; SDT= Stool Deferral Time.
aSeverity for the urgency (sudden or immediate need) to have a bowel movement in the past 24 hours using an 11-point scale ranging from 0 (no urgency) to 10 (worst possible urgency). Mean Week 28 CFB for BU severity was -3.6 times/day.
bHow many times did the patient experience bowel urgency in the past 24 hours. Mean Week 28 CFB for BUF was -3.8 times/day.
cIn the past 24 hours, how many minutes on average could the patient wait from the time they felt the urge to have bowel movement before rushing to the toilet. The shortest weekly SDT is calculated by taking the shortest response (i.e. minimum value) available over the past 7 days, where no urgency is treated as the largest value. |
Conclusion
MIRI showed an early and sustained improvement on BU severity, frequency and stool deferral time through W28 in LUCENT-URGE. MIRI consistently improved clinical outcomes in patients with moderately-to-severely active UC.
References
Dubinsky M, et al. Bowel Urgency in Ulcerative Colitis: Current Perspectives and Future Directions. AJG 2023; 118(11): 1940-53.
Disclosure
SD reports consultancy fees from AbbVie, Alimentiv, Allergan, Amgen, Applied Molecular Transport, AstraZeneca, Athos Therapeutics, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Dr Falk Pharma, Eli lilly and company, Enthera, Ferring Pharmaceuticals Inc., Gilead, Hospira, Inotrem, Janssen, Johnson & Johnson, Morphic, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity Therapeutics, Takeda, Teladoc Health, TiGenix, UCB Inc., Vial, Vifor; lecture fees from AbbVie, Amgen, Ferring Pharmaceuticals Inc., Gilead, Janssen, Mylan, Pfizer, Takeda.
AD reports fees for participation in clinical trials, review activities such as data monitoring boards, statistical analysis and end point committees from Abivax, AbbVie, Bristol Myers Squibb, Dr Falk Foundation, Galapagos, Gilead, Janssen, and Pfizer; consultancy fees from AbbVie, Alfasigma, Amgen, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Dr Falk Foundation, Ferring Pharmaceuticals, Fresenius Kabi, Galapagos, Janssen, Lilly, MSD, Pfizer, Pharmacosmos, Sandoz, Stada, Takeda, Tillotts, and Vifor Pharma; payment from lectures including service on speakers bureaus from AbbVie, Alfasigma, Biogen, CED Service GmbH, Celltrion, Falk Foundation, Ferring, Galapagos, Gilead, High5MD, Janssen, Materia Prima, MedToday, MSD, Pfizer, Streamed-Up, Takeda, Tillotts, and Vifor Pharma; payment for manuscript preparation from Abbvie, Falk Foundation, J & J, Takeda, Thieme, and UniMed Verlag.
DL declares counselling, boards, and transport or fees from AbbVie, Amgen, Biogen, Celltrion, Ferring, Alphasigma, Janssen, Lilly, MSD, Pfizer, Prometheus, Roche, Sandoz and Takeda.
JKL has received consultancy and speaker fees from AbbVie, Abivax, Arena, AlfaSigma, Bristol Myers Squibb, Biohit, Celltrion, Eli Lilly and Company, Ferring, Galapagos, Janssen, MSD, Pfizer, Takeda and Tillotts and research grants from AbbVie, Galapagos and Takeda.
RK reports lecture fees from Aboca S.p.A. Società Agricola, Ferring, AbbVie, and Eli Lilly and Company.
JDL consulted or served on an advisory board or data monitoring committee for Amgen, Arena Pharmaceuticals, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Galapagos, Gilead, Janssen Pharmaceuticals, Merck, Pfizer, Protagonist Therapeutics, Sanofi. He has had research funding or in kind support from Nestle Health Science, Takeda, Janssen Pharmaceuticals, AbbVie and Eli lilly and company. He has had educational grants from Janssen. He has performed legal work on behalf of manufacturers of generic ranitidine and 3M. He owns stock in Dark Canyon Labs.
ZY has received research support from AbbVie, Axcella, Bristol Myers Squibb, CymaBay, Galectin, Intercept, Inventiva, Madrigal, NGM, Novo Nordisk, NST, Poxel, and Sagimet; has acted as a speaker for AbbVie, Intercept, and Bristol Myers Squibb; and as a consultant for Intercept and Madrigal.
EC reports advisory board and consultant for Pfizer, Takeda, and PRIME Education; speaker for AbbVie, Eli Lilly and Company, Janssen, and Takeda.
KA, WJE, TT, IR are employees and minor shareholders of Eli Lilly and Company.
DR reports grant support from Takeda and has served as a consultant for AbbVie, AltruBio, Arena Pharmaceuticals, Bristol Myers Squibb, Eli Lilly and Company, Genentech, Gilead Sciences, Iterative Scopes, Janssen, Pfizer, Prometheus Biosciences, Roche, Takeda, and Techlab.
MD reports consulting fees from AbbVie, Arena Pharmaceuticals, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly and Company, Genentech (Roche), Gilead Sciences, Janssen, Pfizer, Prometheus Biosciences, Roche, Takeda Pharmaceuticals, and UCB; contracted research from AbbVie and Janssen; stock interest in Trellus Health; and licensing fees from Takeda Pharmaceuticals.
