Relationship Between Combined Histologic and Endoscopic Endpoints and Eff i cacy of Ustekinumab Treatment in Patients With Ulcerative Colitis
Relationship Between Combined Histologic and Endoscopic Endpoints and Eff i cacy of Ustekinumab Treatment in Patients With Ulcerative Colitis
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溃疡性结肠炎患者的组织学和内镜联合终点与乌司奴单抗治疗疗效之间的关系
DOI：
10.1053/j.gastro.2020.08.037
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发表时间：
2020-12-01
期刊：
影响因子：
29.4
通讯作者：
De Hertogh, Gert
中科院分区：
文献类型：
--
作者：
Li, Katherine;Marano, Colleen;De Hertogh, Gert
背景与目的：乌司奴单抗诱导并维持溃疡性结肠炎（UC）患者的组织学改善。该终点单独以及与内镜改善联合的临床相关性尚不清楚。方法：在Ustek I 3期UC临床研究中接受治疗的UC患者的2630份结肠活检样本中评价了组织学疾病活动性。我们评估了诱导期（第8周和第16周）和维持期（第44周）结束时组织学改善（定义为小于5%的隐窝中中性粒细胞浸润，且无隐窝破坏、糜烂、溃疡或肉芽组织）与临床终点之间的相关性。我们评估了组织学和内镜（马约内镜分项评分，0或1）改善终点的有效性，我们称之为组织内镜粘膜愈合（或组织内镜粘膜改善）。研究结果：在诱导和维持研究结束时，组织学改善与临床缓解、较低的平均疾病活动评分以及疾病活动的较大改善显著相关（P <0.0001）。当使用更严格的组织学改善定义时，乌司奴单抗在诱导第8周和维持第44周诱导并维持了比安慰剂显著更高的组织学改善率。在接受乌司奴单抗维持治疗的患者中，诱导后组织学改善和内镜下改善与第44周组织内镜下粘膜愈合率、临床缓解率和无皮质类固醇缓解率高10%至20%相关（均P <0.05）。在第44周，61%的诱导治疗后组织内镜粘膜愈合的患者（56/92）达到临床缓解，而39%的患者（9/23，P = 0.0983），34%的患者（24/71，P = .0009）诱导后仅内镜或组织学改善。在接受乌司奴单抗治疗的UC患者中进行的乌司奴单抗治疗计划的数据表明，诱导治疗后实现组织内镜下粘膜愈合与维持治疗结束时疾病活动性低于单独的组织内镜下改善相关。
BACKGROUND & AIMS: Ustekinumab induces and maintains histologic improvement in patients with ulcerative colitis (UC). The clinical relevance of this endpoint alone, and in combination with endoscopic improvement, is unknown. METHODS: Histologic disease activity was evaluated in 2630 colonic biopsy samples from patients with UC treated in the UNIFI phase 3 UC clinical studies of ustekinumab. We evaluated associations between histologic improvement (defined as the composite of neutrophil infiltration in less than 5% of crypts and no crypt destruction, erosions, ulcerations, or granulation tissue) and clinical endpoints at the end of induction (week 8 and 16) and maintenance (week 44) periods. We assessed the validity of a combined histologic and endoscopic (Mayo endoscopy subscore, 0 or 1) improvement endpoint, which we called histo-endoscopic mucosal healing (or histo-endoscopic mucosal improvement). RESULTS: Histologic improvement was significantly (P < .0001) associated with clinical remission, lower mean disease activity scores, and greater improvement in disease activity at the end of induction and maintenance studies. Ustekinumab induced and maintained significantly higher rates of histologic improvement at induction week 8 and maintenance week 44 than placebo when more stringent definitions of histologic improvement were used. Histologic improvement and endoscopic improvement following induction were associated with 10% to 20% higher rates of histo-endoscopic mucosal healing, clinical remission, and corticosteroid-free remission at week 44 (all P < .05) in patients who received ustekinumab maintenance therapy. At week 44, 61% of patients (56/92) with histo-endoscopic mucosal healing after induction therapy achieved clinical remission, versus 39% of patients (9/23, P = .0983) and 34% of patients (24/71, P = .0009) with endoscopic or histologic improvement alone after induction, respectively.CONCLUSION: Data from the UNIFI program of ustekinumab in patients with UC treated with ustekinumab indicated the achievement of histo-endoscopic mucosal healing after induction therapy is associated with lower disease activity at the end of maintenance therapy than either histologic orendoscopic improvement alone.