Department of Biomedicine, Faculty of Medicine of the University of Porto, Porto, Portugal.
Medical Gastroenterology, Eli Lilly and Company, Indianapolis, Indiana.
Clin Gastroenterol Hepatol. 2024 Sep;22(9):1878-1888.e10. doi: 10.1016/j.cgh.2023.11.010. Epub 2023 Nov 20.
BACKGROUND & AIMS: Histologic evaluation of mucosal healing in Crohn's disease is an evolving treatment target. We evaluated histologic outcomes for mirikizumab efficacy and associations with endoscopic and 1-year outcomes.
Biopsy specimens from 1 ileal and 4 colonic segments were evaluated at weeks 0, 12, and 52 from each of the 170 SERENITY participants. Criteria for the weeks 12 and 52 histologic response were no epithelial neutrophils or epithelial damage, or >50% decrease in either the Robarts Histopathology Index or the active Global Histologic Disease Activity Score, and remission (no mucosal neutrophils and no epithelial damage) had to be met in all biopsy specimens. Agreement was evaluated between histologic and endoscopic end points. Associations between 1-year outcomes and week 12 histologic and endoscopic response were evaluated.
At week 12, 1000 mg mirikizumab resulted in greater rates of histologic response (66% vs 27%; P < .001) and remission (26% vs 6%; P < .01) than placebo. Rates were numerically similar at 1 year (mirikizumab pooled response, 46%-69%; remission, 13%-31%). Agreement between week 12 histologic and endoscopic response was 69% (Cohen's kappa coefficient [κ] = 0.40) and remission was 83% (κ = 0.38) in all pooled arms, including placebo. At 1 year, the percentage of participants who received any dose of mirikizumab and achieved endoscopic remission differed by their week 12 response: histologic (20%), endoscopic (25%), combined histology-endoscopy (45%), or neither (4%) (P = .003).
In a post hoc analysis of phase 2 data, mirikizumab induced and sustained histologic response and remission in Crohn's disease over 52 weeks. Early combined histologic-endoscopic response was associated with endoscopic remission after 1 year of treatment with mirikizumab (ClinicalTrials.gov NCT02891226).
克罗恩病黏膜愈合的组织学评估是一个不断发展的治疗目标。我们评估了 mirikizumab 疗效的组织学结果及其与内镜和 1 年结果的关联。
SERENITY 项目的 170 名参与者的每个参与者的第 0、12 和 52 周的 1 个回肠和 4 个结肠节段的活检标本进行了评估。第 12 周和第 52 周组织学反应的标准为上皮中性粒细胞或上皮损伤不存在，或 Robarts 组织病理学指数或活跃的全球组织学疾病活动评分降低超过 50%，并且所有活检标本都必须满足缓解（无黏膜中性粒细胞和无上皮损伤）。评估了组织学和内镜终点之间的一致性。评估了 1 年结果与第 12 周组织学和内镜反应之间的关联。
在第 12 周，1000mg mirikizumab 诱导组织学反应（66% vs 27%；P<0.001）和缓解（26% vs 6%；P<0.01）的发生率显著高于安慰剂。在 1 年时，mirikizumab 汇总反应率（46%-69%）和缓解率（13%-31%）在数值上相似。在所有汇总臂中，包括安慰剂，第 12 周组织学和内镜反应之间的一致性为 69%（Cohen's kappa 系数[κ]为 0.40），缓解率为 83%（κ为 0.38）。在 1 年时，接受任何剂量的 mirikizumab 并达到内镜缓解的参与者百分比因第 12 周的反应而异：组织学（20%）、内镜（25%）、联合组织学-内镜（45%）或两者均无（4%）（P=0.003）。
在 2 期数据的事后分析中，mirikizumab 在 52 周内诱导并维持了克罗恩病的组织学反应和缓解。早期联合组织学-内镜反应与 mirikizumab 治疗 1 年后的内镜缓解相关（ClinicalTrials.gov NCT02891226）。
