Histologic and combined histologic-endoscopic outcomes with mirikizumab in Crohn's disease: VIVID-1 trial results

Evaluation of microscopic inflammation is an emerging therapeutic target of Crohn's disease. The completed VIVID-1 trial evaluated histologic and combined histologic-endoscopic outcomes for mirikizumab relative to placebo and ustekinumab in moderately-to-severely active Crohn's disease.

Two specimens from each of five intestinal segments (one ileal, four colonic) were obtained from the edge of ulcers, or the most inflamed mucosa at screening, and weeks (W)12 and 52. Histologic response was defined as the absence of epithelial neutrophils and epithelial damage, erosions and ulceration or ≥50% decrease in either the active Robarts Histopathology Index or the active Global Histologic Disease Activity Score, and was prespecified. Histologic remission was defined as absence of mucosal neutrophils, no epithelial damage, and no erosions and ulcers and was a prespecified endpoint. Post-hoc analyses included subgroup analyses, the proportions of patients achieving combined histologic-endoscopic outcomes, the agreement between histologic outcomes and endoscopic or clinical outcomes, segmental analyses, the assessment of cut-off points for fecal calprotectin, and the association between W12 histologic outcomes and selected W52 outcomes.

At W12, mirikizumab was superior to placebo for histologic response (P < .0001) and histologic remission (P = .001), with similar rates to ustekinumab (P = .58 and P = .44, respectively). At W52, mirikizumab-treated patients showed greater histologic response (P = .008) compared to ustekinumab, especially in patients who previously failed biologic therapies (P = .006). Combined histologic-endoscopic response at W52 was numerically higher for mirikizumab (P = .06) and reached statistical significance among biologic-failed patients (P = .02); however, combined remission rates were comparable across treatment arms.

Mirikizumab was superior to placebo in achievement of all histology-based endpoints. Mirikizumab showed higher rates compared to ustekinumab for achievement of histologic response at W52. Early histologic response among endoscopic non-responders was associated with 1-year endoscopic outcomes. ClinicalTrials.gov, NCT03926130.