Regueiro Miguel, Fischer Monika, Bossuyt Peter, McGinnis Kim, Protic Marijana, Hunter Gibble Theresa, Panni Tommaso, Chan Lai Shan, Hibi Toshifumi, Rubin David T
Department of Gastroenterology, Hepatology and Nutrition, Cleveland Clinic, Cleveland, OH, USA.
Division of Gastroenterology and Hepatology, Indiana University, Indianapolis, IN, USA.
Inflamm Bowel Dis. 2025 Feb 6;31(2):432-441. doi: 10.1093/ibd/izae166.
Fatigue is a burdensome, under-recognized, multidimensional symptom experienced by patients with Crohn's disease (CD). We evaluated the impact of mirikizumab on fatigue and the association between changes in select patient-reported outcomes and clinical measures with changes in fatigue from baseline to week 104 (W104).
Patients (N = 191) were randomized (2:1:1:2) to receive placebo (PBO), 200 mg, 600 mg, or 1000 mg of mirikizumab, administered intravenously (IV) every 4 weeks at W0, W4, and W8. Patients who achieved ≥1 point improvement in Simple Endoscopic Score for Crohn's Disease (SES-CD) and received mirikizumab at W12 (rerandomized maintenance cohort) were rerandomized to continue induction IV treatment assignment (IV-C) or received 300 mg of mirikizumab subcutaneously (SC) until W52. Nonrandomized maintenance cohort had endoscopic nonimprovers (1000 mg) and PBO patients (PBO/1000 mg) who received 1000 mg of mirikizumab until W52. Subjects from the maintenance period with clinical benefit received 300 mg SC Q4W from W52 to W104. The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) questionnaire was used to assess fatigue, and the FACIT-F associations were assessed using Pearson correlation coefficient.
At W12, mirikizumab groups reported improved FACIT-F scores compared with PBO, and improvement was maintained through W52 and W104. Changes in FACIT-F at W52 and W104 had strong correlations with changes at the same time point in quality of life (QoL) scores but lacked correlations with changes in inflammatory biomarkers.
Mirikizumab treatment significantly improved fatigue in patients with moderately to severely active CD, which was sustained to W104. The improvement in fatigue was correlated with improvement in clinical measures and was strongly correlated with improvement in QoL.
疲劳是克罗恩病（CD）患者经历的一种负担沉重、未得到充分认识的多维症状。我们评估了mirikizumab对疲劳的影响，以及从基线到第104周（W104），特定患者报告结局和临床指标的变化与疲劳变化之间的关联。
患者（N = 191）被随机分组（2:1:1:2），接受安慰剂（PBO）、200 mg、600 mg或1000 mg的mirikizumab，在第0周、第4周和第8周每4周静脉注射（IV）一次。在克罗恩病简易内镜评分（SES-CD）中改善≥1分且在第12周接受mirikizumab治疗的患者（重新随机化维持队列）被重新随机分组，继续接受诱导IV治疗方案（IV-C）或皮下注射（SC）300 mg的mirikizumab直至第52周。非随机维持队列包括内镜检查无改善者（1000 mg）和接受1000 mg mirikizumab直至第52周的PBO患者（PBO/1000 mg）。维持期有临床获益的受试者从第52周至第104周每4周接受300 mg SC治疗。使用慢性病治疗功能评估-疲劳（FACIT-F）问卷评估疲劳，并使用Pearson相关系数评估FACIT-F的相关性。
在第12周时，与PBO相比，mirikizumab组报告FACIT-F评分有所改善，且这种改善维持至第52周和第104周。第52周和第104周时FACIT-F的变化与同一时间点的生活质量（QoL）评分变化有很强的相关性，但与炎症生物标志物的变化缺乏相关性。
Mirikizumab治疗显著改善了中度至重度活动性CD患者的疲劳，这种改善持续至第104周。疲劳的改善与临床指标的改善相关，且与QoL的改善密切相关。
