Division of Pediatric Gastroenterology, Susan and Leonard Feinstein IBD Clinical Center, Icahn School of Medicine at Mount Sinai, New York, USA.
Section of Pediatric Gastroenterology, Hepatology and Nutrition, Comer Children's Hospital at the University of Chicago, 5839 S Maryland Avenue, MC 4065, Chicago, IL, 60637, USA.
Dig Dis Sci. 2024 May;69(5):1826-1833. doi: 10.1007/s10620-024-08379-9. Epub 2024 Mar 23.
Data are limited on the safety and efficacy of combining advanced therapies for refractory patients with IBD.
To evaluate the real-world efficacy and safety of dual advanced therapy (DAT), combining 2 biologics or a biologic with a small molecule, in children and young adults with refractory IBD.
Primary outcome of this single IBD center cohort was DAT remission (clinical and biomarker remission) at first assessment (T1). Secondary outcomes included remission at T2, if DAT de-intensification (De-I) occurred and T3, if T2 DAT re-intensification (Re-I) occurred. Efficacy and safety outcomes were described.
Of the 30 patients [43% female, 30% CD, median age of 18.3 [15.1-19.8] years], all 11 UST + TOFA achieved T1 remission; 6/10 De-I failed at T2; and 4/4 Re-I achieved T3 remission. Of 9 VDZ + TOFA, 6 achieved T1 remission; 5/6 De-I failed at T2; and 1/1 failed T3 Re-I. Of 4 UST + VDZ, 3 achieved T1 remission; 2/3 De-I failed at T2; and 0 had Re-I. Of 5 UST + UPA, 4 achieved T1 remission; 1/5 De-I failed at T2 but recaptured T3 remission post-Re-I. One VDZ + OZA achieved T1 remission and maintained T2 remission post-De-I to OZA monotherapy. At last follow-up, 43% were on original DAT, 17% on one of original DAT, and 40% neither. One UST + TOFA patient developed mild leukopenia and another developed septic arthritis and venous thromboembolism on VDZ + TOFA and prednisone.
Most children and young adults treated with DAT achieved remission with minimal safety events; however, de-intensification had limited success.
关于联合应用高级治疗方案治疗难治性炎症性肠病（IBD）患者的安全性和疗效，目前数据有限。
评估联合应用两种生物制剂或生物制剂联合小分子药物的双重高级治疗方案（DAT）在儿童和青少年难治性 IBD 中的真实世界疗效和安全性。
该单中心队列研究的主要结局为首次评估（T1）时 DAT 缓解（临床和生物标志物缓解）。次要结局包括 T2 缓解，如果 DAT 减药（De-I），则包括 T3 缓解，如果 T2 DAT 再强化（Re-I），则包括 T3 缓解。描述了疗效和安全性结局。
30 例患者中（43%为女性，30%为 CD），11 例 UST+TOFA 均达到 T1 缓解；6/10 例 De-I 在 T2 时失败；4/4 例 Re-I 在 T3 时达到缓解。9 例 VDZ+TOFA 中，6 例达到 T1 缓解；5/6 例 De-I 在 T2 时失败；1 例在 T3 时 Re-I 失败。4 例 UST+VDZ 中，3 例达到 T1 缓解；2/3 例 De-I 在 T2 时失败；0 例在 T3 时再强化。5 例 UST+UPA 中，4 例达到 T1 缓解；1/5 例 De-I 在 T2 时失败，但在 Re-I 后再次达到 T3 缓解。1 例 VDZ+OZA 达到 T1 缓解，并在 De-I 后维持 OZA 单药治疗的 T2 缓解。最后一次随访时，43%的患者仍使用原始 DAT，17%的患者使用一种原始 DAT，40%的患者未使用任何 DAT。1 例 UST+TOFA 患者在接受 VDZ+TOFA 和泼尼松治疗时出现轻度白细胞减少，另 1 例出现败血症性关节炎和静脉血栓栓塞。
大多数接受 DAT 治疗的儿童和青少年达到缓解，安全性事件较少；然而，减药的效果有限。
