Fumery Mathurin, Peyrin-Biroulet Laurent, Nancey Stephane, Altwegg Romain, Gilletta Cyrielle, Veyrard Pauline, Bouguen Guillaume, Viennot Stephanie, Poullenot Florian, Filippi Jerome, Buisson Anthony, Bozon Anne, Brazier Franck, Pouillon Lieven, Flourie Bernard, Boivineau Lucile, Siproudhis Laurent, Laharie David, Roblin Xavier, Diouf Momar, Treton Xavier
Department of Gastroenterology, and PeriTox, UMR I0-I, Amiens University Hospital, Amiens, France.
INSERM U1256 NGERE, Department of Gastroenterology, Nancy University Hospital, Lorraine University, Nancy, France.
J Crohns Colitis. 2020 Sep 8. doi: 10.1093/ecco-jcc/jjaa177.
The approved maintenance regimens for ustekinumab in Crohn's disease (CD) are 90 mg every 8 or 12 weeks. Some patients will partially respond to ustekinumab or will experience a secondary loss of response. It remains poorly known if these patients may benefit from shortening the interval between injections.
All patients with active CD, as defined by Harvey-Bradshaw score ≥ 4 and one objective sign of inflammation (CRP > 5 mg/L and/or fecal calprotectin > 250 µg/g and/or radiologic and/or endoscopic evidence of disease activity) who required ustekinumab dose escalation to 90mg every 4 weeks for loss of response or incomplete response to ustekinumab 90mg every 8 weeks were included in this retrospective multicenter cohort study.
One hundred patients, with a median age of 35 years (Interquartile Range (IQR), 28 - 49) and median disease duration of 12 (7 - 20) years were included. Dose intensification was performed after a median of 5.0 (2.8 - 9.0) months of ustekinumab treatment and was associated with corticosteroids and immunosuppressants in respectively 29% and 27% of cases. Short-term clinical response and clinical remission were observed in respectively 61% and 31% after a median of 2.4 (1.3 - 3.0) months. After a median follow-up of 8.2 (5.6-12.4) months, 61% of patients were still treated with ustekinumab, and 26% in steroid-free clinical remission. Among the 39 patients with colonoscopy during follow-up, 14 achieved endoscopic remission (no ulcers). At the end of follow-up, 27% of patients were hospitalized, and 19% underwent intestinal resection surgery. Adverse events were reported in 12% of patients, including five serious adverse events.
In this multicenter study, two-thirds of patients recaptured response following treatment intensification with ustekinumab 90 mg every 4 weeks.
优特克单抗治疗克罗恩病（CD）的批准维持方案是每8周或12周注射90mg。一些患者对优特克单抗仅部分应答，或会出现继发性应答丧失。这些患者是否能从缩短注射间隔中获益仍知之甚少。
本项回顾性多中心队列研究纳入了所有符合以下条件的活动性CD患者：Harvey-Bradshaw评分≥4且有一项炎症客观指标（CRP>5mg/L和/或粪便钙卫蛋白>250μg/g和/或疾病活动的影像学和/或内镜证据），因对每8周一次90mg优特克单抗治疗应答丧失或应答不完全而需要将优特克单抗剂量增加至每4周90mg。
共纳入100例患者，中位年龄35岁（四分位间距[IQR]，28 - 49岁），中位病程12（7 - 20）年。在优特克单抗治疗中位5.0（2.8 - 9.0）个月后进行了剂量强化，分别有29%和27%的病例联合使用了皮质类固醇和免疫抑制剂。在中位2.4（1.3 - 3.0）个月后，分别有61%和31%的患者观察到短期临床应答和临床缓解。在中位随访8.2（5.6 - 12.4）个月后，61%的患者仍在接受优特克单抗治疗，26%的患者处于无类固醇临床缓解状态。在随访期间接受结肠镜检查的39例患者中，14例达到内镜缓解（无溃疡）。随访结束时，27%的患者住院治疗，19%的患者接受了肠切除手术。12%的患者报告了不良事件，包括5例严重不良事件。
在这项多中心研究中，三分之二的患者在强化治疗为每4周一次90mg优特克单抗后恢复了应答。
