Background

Adalimumab (ADA) is efficacious and well tolerated in adult patients with ulcerative colitis (UC).^1,2 SERENE-UC (NCT02065622) is a study evaluating higher ADA dosing regimens from which induction study results have previously been reported³; here, we report data from the maintenance study.

Methods

This Phase 3, double-blind, randomised, multicentre study evaluated higher vs. standard ADA dosing regimens for induction and maintenance therapy in adult patients with moderately to severely active UC. Following completion of the induction study at Week 8, all patients were re-randomised 2:2:1 to ADA 40 mg every week (40 EW), ADA 40 mg every other week (40 EOW), or exploratory ADA 40 mg with therapeutic drug monitoring (TDM) regimens, stratified by induction treatment regimen, clinical response status at Week 8, and clinical remission (CRem) status at Week 8 among Week 8 responders. Efficacy endpoints were evaluated in Week 8 responders (ITT-RP) unless indicated differently. The primary efficacy endpoint was proportion of patients achieving CRem (full Mayo Score ≤2 with no subscore >1) at Week 52. The endoscopic component of the Mayo Score was scored via central reading. Non-responder imputation was used for missing values. Comparisons between 40 EW and 40 EOW dosing regimens used the Cochran–Mantel–Haenszel test adjusted for stratification. Safety assessment included a collection of adverse events (AEs), vital signs, and laboratory data.

Results

Of 852 patients in the Global (ex-Japan) induction study, 757 were re-randomised at Week 8 and 371 were included in the ITT-RP. In the ITT-RP, induction baseline demographics and disease characteristics were generally balanced across the 3 treatment arms; range across arms for mean UC disease duration was 6.2–7.8 years, 6.8–11.7% had prior infliximab use, and 62.5–63.5% were receiving corticosteroids. The overall mean ADA exposure was 252.2 days. The table displays results for efficacy endpoints. The observed safety profile was similar between maintenance treatment arms, including AEs of special interest (generally <1% across arms).

Conclusion

In the Global (ex-Japan) study of SERENE-UC, CRem at Week 52 was numerically higher among Week 8 responders in patients receiving ADA 40 EW compared with 40 EOW maintenance regimens (∆ = 10.5%), but not statistically significant. Higher maintenance treatment with 40 EW was generally safe and well tolerated with a similar safety profile to 40 EOW. No new long-term safety concerns were observed.

References

• Reinisch W, et al. Gut, 2011;60:780–7.
• Sandborn WJ, et al. Gastroenterology, 2012;142:257–65.
• Panés J, et al. UEG Journal, 2019;7(Suppl. 8):OP216.

中文翻译：

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OP01中度至重度溃疡性结肠炎患者的阿达木单抗维持治疗方案比标准方案高：SERENE-UC维持研究的结果

背景

阿达木单抗（ADA）对溃疡性结肠炎（UC）的成年患者有效且耐受良好。^1,2 SERENE-UC（NCT02065622）是一项评估更高的ADA给药方案的研究，先前已报道了该方案的诱导研究结果³；在这里，我们报告维护研究的数据。

方法

这项3期，双盲，随机，多中心研究评估了在中度至重度活动性UC成年患者中诱导和维持治疗的ADA给药方案高于标准ADA给药方案。在第8周完成诱导研究后，将所有患者按2：2：1重新随机分配至ADA 40 mg /周（40 EW），ADA 40 mg /隔周（40 EOW）或探索性ADA 40 mg治疗药物监测（TDM）方案，按诱导治疗方案，第8周的临床反应状态以及第8周的应答者在第8周的临床缓解（CRem）状态进行分层。除非另有说明，否则在第8周缓解者（ITT-RP）中评估疗效终点​​。主要疗效终点是在52周时达到CRem（完全Mayo得分≤2，且子评分不大于1）的患者比例。Mayo评分的内窥镜成分通过中央阅读进行评分。无响应插补用于缺失值。在40种EW和40种EOW给药方案之间的比较使用了针对分层调整的Cochran–Mantel–Haenszel试验。安全评估包括不良事件（AE），生命体征和实验室数据的收集。

结果

在全球（日本除外）入职研究的852名患者中，有757名在第8周被重新随机分配，ITT-RP中包括了371名患者。在ITT-RP中，在3个治疗组中，诱导基线人口统计学特征和疾病特征总体上是平衡的。UC病程的平均间隔为6.2–7.8年，先前使用英夫利昔单抗的患者为6.8–11.7％，接受糖皮质激素的患者为62.5–63.5％。ADA的总体平均暴露时间为252.2天。该表显示功效终点的结果。维持治疗组之间观察到的安全性特征相似，包括具有特殊意义的不良事件（各组之间通常<1％）。

结论

在SERENE-UC的全球（日本除外）研究中，接受ADA 40 EW的患者在第52周的CRem在第8周应答者中的数值高于40种EOW维持方案（∆ = 10.5％），但无统计学意义。一般而言，使用40 EW进行高级维护治疗是安全的，并且耐受性良好，其安全性与40 EOW相似。没有发现新的长期安全隐患。

参考文献

• Reinisch W等。肠道，2011年； 60：780-7。
• Sandborn WJ等。胃肠病学，2012； 142：257-65。
• PanésJ等。UEG Journal，2019; 7（Suppl.8）：OP216。