Division of Gastroenterology, Hepatology, and Nutrition, The Children's Hospital of Philadelphia.
Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
J Pediatr Gastroenterol Nutr. 2021 Sep 1;73(3):e57-e62. doi: 10.1097/MPG.0000000000003190.
Tofacitinib, a selective Janus kinase inhibitor, effectively induces and maintains remission in adults with inflammatory bowel disease (IBD), but data are limited in children. This study aimed to evaluate the efficacy and safety of tofacitinib for medically refractory pediatric-onset IBD.
This single-center retrospective study included subjects ages 21 years and younger who started tofacitinib for medically refractory IBD. Clinical activity indices, clinical response, steroid-free remission, biochemical response, and adverse events (AEs) were evaluated over 52 weeks.
Twenty-one subjects, 18 with ulcerative colitis or indeterminate IBD, received tofacitinib. At the end of the 12-week induction period, 9 out of 21 (42.9%) subjects showed clinical response and 7 out of 21 (33.3%) were in steroid-free remission. Of evaluable subjects at 52 weeks, 7 out of 17 (41.2%) showed clinical response and were in steroid-free remission. Of those remaining on tofacitinib at 1 year, none required concomitant systemic corticosteroids. Tofacitinib was discontinued in 8 subjects because of refractory disease, including 8 who ultimately underwent colectomy, and in 1 subject who developed a sterile intra-abdominal abscess. There were no instances of thrombi, zoster reactivation, or clinically significant hyperlipidemia, all of which were AEs of interest.
There is limited experience with tofacitinib in pediatric IBD. In this cohort, tofacitinib induced rapid clinical response with sustained efficacy in nearly half of subjects. This study provides encouraging evidence for the efficacy and safety of tofacitinib as part of the treatment paradigm for young individuals with moderate-to-severe IBD. Larger, well-powered, prospective studies are warranted.
托法替布是一种选择性 Janus 激酶抑制剂，能有效诱导并维持成人炎症性肠病（IBD）缓解，但儿童数据有限。本研究旨在评估托法替布治疗儿童难治性 IBD 的疗效和安全性。
这是一项单中心回顾性研究，纳入了开始使用托法替布治疗儿童难治性 IBD 的 21 岁及以下患者。在 52 周期间评估临床活动指数、临床应答、无激素缓解、生化应答和不良事件（AE）。
21 例患者（18 例溃疡性结肠炎或不确定 IBD）接受了托法替布治疗。在 12 周诱导期结束时，21 例患者中有 9 例（42.9%）出现临床应答，7 例（33.3%）达到无激素缓解。在 52 周时可评估的患者中，7 例（41.2%）出现临床应答并处于无激素缓解状态。在 1 年时仍使用托法替布的患者中，无人需要同时使用全身皮质激素。由于疾病难治，8 例患者（最终 8 例患者接受了结肠切除术）和 1 例患者（发生无菌性腹腔脓肿）停用了托法替布。没有血栓、带状疱疹再激活或临床上显著的血脂异常的病例，这些都是关注的 AE。
托法替布在儿科 IBD 中的应用经验有限。在本队列中，托法替布在近一半的患者中迅速诱导临床应答，并保持疗效。本研究为托法替布作为中重度 IBD 年轻患者治疗方案的一部分的疗效和安全性提供了令人鼓舞的证据。需要更大、更有力的前瞻性研究。
