Efficacy and safety of duvakitug in patients with ulcerative colitis (RELIEVE UCCD): a phase 2b, randomised, placebo-controlled trial.

We aimed to investigate the efficacy and safety of duvakitug, an anti-TNF-like cytokine 1A (TL1A) monoclonal antibody, in adults with moderately to severely active ulcerative colitis.

我们的目标是研究抗TNF样细胞因子1A（TL1A）单克隆抗体duvakitug在中度至重度活动性溃疡性结肠炎成人患者中的疗效和安全性。

Methods

In this multicentre, placebo-controlled, phase 2b study, we randomly assigned (1:1:1) adults aged 18-75 years with moderately to severely active ulcerative colitis (including patients with inadequate response, loss of response, or intolerance to previous conventional or advanced therapies) to receive a 2250 mg loading dose of duvakitug (subcutaneously), followed by either 450 mg or 900 mg doses every 2 weeks, or placebo loading dose followed by placebo every 2 weeks.

在这项多中心、安慰剂对照的2b期研究中，我们随机分配（1:1:1）18-75岁的成人患者，这些患者患有中度至重度活动性溃疡性结肠炎（包括对先前常规或先进疗法反应不足、反应丧失或不耐受的患者），接受2250 mg的duvakitug负荷剂量（皮下注射），随后每两周接受450 mg或900 mg剂量，或接受安慰剂负荷剂量后每两周接受安慰剂。

The primary endpoint was clinical remission (modified Mayo score) at week 14, analysed using Bayesian methodology.

主要终点是第14周的临床缓解（改良Mayo评分），使用贝叶斯方法进行分析。

A duvakitug dose was declared successful if the posterior probability that the response rate exceeded placebo was 0·90 or greater.

如果后验概率表明反应率超过安慰剂的概率达到0.90或更高，则认为duvakitug剂量是成功的。

Analyses were done in the modified intention-to-treatpopulation, which included all patients who received at least one dose of their assigned treatment.

分析是在修改后的意向治疗人群中进行的，该人群包括所有至少接受了一次分配治疗的患者。

This trial was registered with ClinicalTrials.gov, NCT05499130, and has been completed.

该试验已在ClinicalTrials.gov上注册，注册号为NCT05499130，并已完成。

Results

Patients were enrolled between Sept 30, 2022 and Nov 12, 2024.

患者入组时间为2022年9月30日至2024年11月12日。

We screened 260 patients with ulcerative colitis.

我们筛查了260名患有溃疡性结肠炎的患者。

Of these, we randomly assigned 137 (53%) patients to receive duvakitug (n=47 450 mg and n=46 900 mg) or placebo (n=44; modified intention-to-treatanalysis set).

在这些患者中，我们随机分配了137名（占53%）患者接受duvakitug治疗（47名患者接受450毫克剂量，46名患者接受900毫克剂量）或安慰剂治疗（44名患者；改良意向治疗分析集）。

Patients had a mean age of 41·0 years (SD 13·1); 86 (63%) were men, 51 (37%) were women, and 132 (96%) were White. 43 (31%) patients had previous exposure to an approved advanced therapy. 17 (36%) of 47 patients in the duvakitug 450 mg group and 22 (48%) of 46 patients in the duvakitug 900 mg group were in clinical remission at week 14, compared with nine (20%) of 44 patients in the placebo group.

患者的平均年龄为41.0岁（标准差13.1）；86名（63%）为男性，51名（37%）为女性，132名（96%）为白人。43名（31%）患者之前接受过批准的高级治疗。在第14周时，47名患者中有17名（36%）和46名患者中有22名（48%）分别在duvakitug 450 mg组和duvakitug 900 mg组达到临床缓解，而对照组44名患者中仅9名（20%）达到临床缓解。

Differences in posterior mean response rates versus placebo were 15% (95% credible interval [CrI] -3 to 33) for duvakitug 450 mg and 26% (95% CrI 8 to 44) for duvakitug 900 mg, with posterior probabilities of superiority to placebo exceeding the prespecified threshold for declaring efficacy (0·95 in the 450 mg group and >0·99 in the 900 mg group).

与对照组相比，duvakitug 450 mg组的后验平均反应率差异为15%（95%可信区间[CrI] -3至33），duvakitug 900 mg组为26%（95% CrI 8至44），后验概率显示duvakitug 450 mg组和duvakitug 900 mg组均优于对照组，超过了声明疗效的预设阈值（duvakitug 450 mg组为0.95，duvakitug 900 mg组超过0.99）。

Adverse eventincidencewas similar with duvakitug (23 [49%] of 47 patients in the 450 mg group and 20 [43%] of 46 in the 900 mg group) and placebo (23 [52%] of 44).

不良事件的发生率在duvakitug组中相似（450 mg组47名患者中有23名[49%]，900 mg组46名患者中有20名[43%]）与安慰剂组（44名患者中有23名[52%]）相似。

The most frequently occurring adverse events were anaemia (one in the 450 mg group, one in the 900 mg group, and three in the placebo group) and upper respiratory tract infection (three in the 450 mg group, one in the 900 mg group, and one in the placebo group).

最常见的不良事件是贫血（450 mg组1例，900 mg组1例，安慰剂组3例）和上呼吸道感染（450 mg组3例，900 mg组1例，安慰剂组1例）。

One serious adverse eventoccurred in the 900 mg group (non-infective oophoritis) and one in the placebo group (intracranial haemorrhage).

900 mg组发生了一例严重不良事件（非感染性卵巢炎），安慰剂组发生了一例（颅内出血）。

interpretation

Duvakitug showed significant evidence for clinical remission versus placebo, with no safety concerns identified, in patients with moderately to severely active ulcerative colitis.

Duvakitug在中度至重度活动性溃疡性结肠炎患者中，与安慰剂相比，显示出临床缓解的显著证据，且未发现安全问题。

funding

Teva and Sanofi.

梯瓦和赛诺菲。