Mirikizumab effect on bowel urgency resolution in a randomised controlled phase 3 trial of participants with crohn’s disease

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 intensity. 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 reported.

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). 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 1]). A nominally significantly greater proportion of miri-treated patients achieved W52 BU CMI-composite and BU remission-composite ([Table 1]). Similar results were seen with BL UNRS≥6.

Table 1 

		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.

 

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Publication History

Article published online:
04 September 2025