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Therapeutic Effect of Infliximab in the Treatment of Severe/Refractory Intestinal Behcet's Disease: A Single-center Retrospective Study
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摘要:
目的 探讨英夫利西单克隆抗体(infliximab, IFX)治疗重症/难治性肠型白塞病(Behcet's disease, BD)的疗效及安全性。 方法 回顾性分析2012年9月至2018年11月, 北京协和医院风湿免疫科收治的因前期治疗无效而联合应用IFX的重症/难治性肠型BD患者临床资料, 包括临床表现、内镜下表现及病理、影像学检查、IFX联合治疗前后用药、治疗反应及预后。分析并比较联合用药前后症状改善及内镜下溃疡愈合情况, 采用配对t检验比较治疗前后红细胞沉降率、C反应蛋白、肠型BD疾病活动指数(disease activity index for intestinal BD, DAIBD)及糖皮质激素剂量的变化。 结果 12例BD患者纳入本研究, 其中男性10例, 女性2例, 平均年龄(29.5±10.5)岁, 均为活动性肠道受累BD, 确诊BD到开始IFX联合治疗的中位时间为27.0(4.3, 109.5)个月。12例患者均存在腹痛、消化道溃疡, 其中8例腹泻, 11例并发消化道出血, 4例肠梗阻, 3例肠穿孔。联合应用IFX后, 12例患者症状均得到改善, 溃疡渐愈合, 消化道出血好转, 1例穿孔患者同时行手术治疗, 1例患者缓解后出现结肠狭窄择期行梗阻肠段切除术。IFX联合治疗后, 红细胞沉降率[4.0(2.0, 6.8)mm/h比28.5(10.3, 52.3)mm/h, P＜0.01]、C反应蛋白[0.6(0.5, 1.7)mg/dl比26.8(9.1, 47.1)mg/dl, P＜0.01]、DAIBD(37.5±27.3比126.7±49.0, P＜0.01)和糖皮质激素剂量[13.8(1.9, 16.9)mg/d比40.0(16.3, 56.3)mg/d, P＜0.01]较治疗前显著下降。免疫抑制剂种类减少或不变。未观察到严重感染或药物不良反应。 结论 IFX联合糖皮质激素/免疫抑制剂对治疗严重/难治性肠BD安全、有效且耐受性良好。 Abstract:Objective The aim of this study was to explore the efficacy and safety of infliximab (IFX) for severe/refractory intestinal Behcet's disease (BD). Methods The clinical data of intestinal BD patientstreated with IFX from September 2012 to November 2018 in Peking Union Medical College Hospital were retrospectively collected and analyzed, including clinical manifestations, endoscopic manifestations and pathology, imaging examinations, medication before and after IFX treatment, treatment response and prognosis. The clinical symptoms and endoscopic ulcer healing before and after treatment were analyzed and compared. Meanwhile, the changes of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), disease activity index for intestinal BD (DAIBD), and the dosage of glucocorticoid before and after IFX treatment were compared by paired t-test. Results Twelve patients (10 males and 2 females) were enrolled, with a mean age of (29.5±10.5) years old; all were active with intestinal BD. The median time between diagnosis of BD and initiation of IFX therapy was 27.0(4.3, 109.5)months. All patients had abdominal pain and gastrointestinal ulcer, in which 8 cases with diarrhea, 11 with gastrointestinal bleeding, 4 with intestinal obstruction, and 3 with intestinal perforation were documented. After using IFX, the symptoms of all the patients were improved; the ulcers gradually healed; the gastrointestinal bleeding stopped. One patient with intestinal perforation was conducted surgery at the same time, and another with colonic stenosis after remission received ileus segmentectomy. The ESR level[4.0(2.0, 6.8)mm/h vs. 28.5(10.3, 52.3)mm/h, P < 0.01], CRP level[0.6(0.5, 1.7)mg/dl vs. 26.8(9.1, 47.1)mg/dl, P < 0.01], DAIBD(37.5±27.3 vs. 126.7±49.0, P < 0.01], and the dosage of glucocorticoid[13.8(1.9, 16.9)mg/d vs. 40.0(16.3, 56.3)mg/d, P < 0.01] were significantly decreased. Furthermore, the types of immunosuppressants being used were gradually decreased or unchanged. No serious infectious and adverse events were observed. Conclusion IFX, in combination with corticosteroids and immunosuppressants, is safe, effective, and well tolerated for severe/refractory intestinal BD. -
Key words:
- intestinal Behcet's disease /
- infliximab /
- efficacy /
- safety
利益冲突 无孟德钎、李璐对本文同等贡献, 孟德钎现在南京医科大学附属淮安第一医院风湿免疫科工作 -
表 1 12例肠白塞病联合应用英夫利西单克隆抗体治疗前后的临床及用药特点
序号 性别 年龄
(岁)既往用药 消化系统病变 联合应用IFX 不良反应 随访时间
(月)药物 免疫抑制剂种类(n) 部位 并发症 内镜下表现 剂量
(mg)疗程
(次)联合用药 免疫抑制剂种类
(n)消化道症状 1 女 31 无 0 回盲部 出血 巨大溃疡 200 12 Thd、SSZ 2 症状消失，溃疡愈合 无 18 2 男 46 GC、MTX、Thd、CTX 3 胃、末端回肠、升结肠 出血、梗阻 多发深大溃疡 300 4 GC、CTX、Thd 2 症状消失，溃疡愈合 无 5 3 男 14 GC、IVIG 1 末端回肠、全结肠 出血 多发溃疡 300 6 GC、CsA 1 症状消失，溃疡愈合 无 6 4 男 21 GC、CTX 1 回、盲肠，升、横结肠 出血 多发溃疡 300 5 GC、CTX 1 症状消失，溃疡愈合 无 8 5 男 25 GC、CTX、AZA、Thd、FK-506 4 胃、盲肠、全结肠 出血、梗阻、胃肠穿孔 多发溃疡 300 2 GC、CsA、Thd 2 症状减轻，肠穿孔行小肠部分切除 无 1 6 男 43 GC、Thd、AZA 2 胃、乙状结肠 出血 巨大溃疡 300 3 GC、Thd、AZA 2 症状消失 过敏1次 1 7 男 26 GC、CTX、SSZ、MTX 3 回盲部 梗阻 多发溃疡 200 6 GC、AZA、CTX、MTX 3 症状消失 无 7 8 男 38 GC、CTX、AZA、SSZ、Thd 4 回盲部 出血 深大溃疡 300 9 GC、Thd、CTX、SSZ 3 症状消失，溃疡愈合 无 22 9 男 39 GC、CTX 1 末端回肠 出血 多发溃疡 200 5 GC、AZA、CTX 2 症状消失，溃疡愈合 无 7 10 女 14 GC、CTX、HCQ、CsA 3 末端回肠 出血、肠穿孔 巨大溃疡 200 23 GC、MTX、SSZ、Thd 3 溃疡渐愈合，肉芽形成 无 62 11 男 32 GC、CTX、Thd 2 升结肠 出血、梗阻 巨大溃疡 300 4 AZA、SSZ、Thd 3 溃疡愈合，肠腔狭窄手术后缓解 无 4 12 男 24 GC、CTX、Thd 2 回盲部、直肠 出血 巨大溃疡 300 4 GC、Thd 1 症状消失 无 5 GC：糖皮质激素；MTX：甲氨喋呤；Thd：沙利度胺；CTX：环磷酰胺；HCQ：硫酸羟氯喹；CsA：环孢素A；SSZ：柳氮磺吡啶；FK-506:他克莫司；AZA:硫唑嘌呤；症状消失：无腹痛、腹泻、出血 
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