Effects of mirikizumab versus placebo on histologic inflammation evaluated by comprehensive assessment in 5 intestinal segments in a randomized controlled phase 3 trial of participants with Crohn’s disease

Introduction: Mirikizumab (MIRI) increased histologic response (H-Res) and remission (H-Rem) relative to placebo (PBO) in the Phase 2 SERENITY trial.

Methods: We compared the effect of MIRI on H-Res and H-Rem at week (W)12 and W52 to PBO by composite endpoints of response (clinical response by Patient-Reported Outcome [PRO] at W12 and W52 H-Res) and of remission (clinical response by PRO at W12 and W52 H-Rem) at W52. The overall population of patients with moderately-to-severely active Crohn’s Disease (CD), including those without prior biologic failure (non-BF), and those with prior BF were assessed, using data from the Phase 3 VIVID-1 trial (NCT03926130). Two biopsy specimens from each of the five intestinal segments (one ileal and four colonic) were obtained from the edge of ulcers, or the most inflamed mucosa from randomized patients at screening, W12, and W52. Clinical response by PRO was defined as≥30% decrease in stool frequency and/or abdominal pain with neither score worse than baseline.

Results At W12, treatment with MIRI resulted in nominally statistically significantly higher rates of H-Res in all three patient groups analyzed (p<.001) ([Table 1]). At W12, differences between MIRI vs PBO were nominally significant in achieving H-Rem in all patients (p<.01) and in non-BF and BF patients (both p<.05). For W52 composite H-Res, differences between MIRI vs PBO were nominally statistically significant in all patient groups examined (p<.001). For W52 composite H-Rem, nominally statistically significant differences between MIRI vs PBO were observed in all patients (p<.001), in non-BF patients (p<.05), and in BF patients (p<.001).

Table 1 

	All patients			Without Prior Biologic failure			With Prior Biologic Failure
	PBO (N=199)	MIRI (N=579)	Difference (95% CI)	PBO (N=91)	MIRI (N=273)	Difference (95% CI)	PBO (N=88)	MIRI (N=255)	Difference (95% CI)
W12 H-Res	30.7	52.7	22.2 (14.6-29.7)***	37.4	58.6	21.2 (9.7-32.8)***	22.7	47.8	25.1 (14.4-35.8)***
W12 H-Rem	12.1	22.1	10.2 (4.7-15.7)**	14.3	27.5	13.2 (4.3-22.1)*	4.5	12.2	7.6 (1.7-13.5)*
W52 Composite H-Res	16.1	44.4	28.2 (21.6-34.7)***	26.4	46.5	20.1 (9.3-31.0)***	6.8	45.9	39.1 (31.0-47.1)***
W52 Composite H-Rem	8.5	23.3	14.7 (9.5-19.9)***	14.3	24.9	10.6 (1.8-19.5)*	2.3	21.6	19.3 (13.4-25.2)***

Data are%;*p<.05; ** p<.01;*** p<.001 vs PBO “Without prior biologic failure“ and “With prior biologic failure“ were subgroups of all patients with active histologic disease at baseline. P-values for “All patients” were from the Cochran–Mantel–Haenszel test adjusting for baseline covariates. P-values for the “Without prior biologic failure“ and “With prior biologic failure“ subgroups were from the Fisher&apos;s exact test. H-Res=absence of epithelial neutrophils and epithelial damage, erosions, and ulceration or≥50% decrease in either the sum of the 5 segments of Robarts Histopathology Index or the Global Histologic Disease Activity Score. H-Rem=complete absence of mucosal neutrophils (in epithelium and lamina propria), and no epithelial damage, erosions, and ulcers. CI=confidence interval; H=histologic; MIRI=mirikizumab; PBO=placebo; Rem=remission; Res=response; W=week

Conclusions: Based upon strict definitions that applied to all 5 intestinal segments, MIRI achieved nominally significantly higher rates of H-Res and H-Rem compared to PBO in all patients at W12 and W52. The statistical difference was more pronounced in the BF population after one year of treatment.

Publikationsverlauf

Artikel online veröffentlicht:
04. September 2025