FT3、FT4、FT3/FT4、TSH与克罗恩病维得利珠单抗治疗后临床活动度变化关系的研究-东南大学学报医学版

FT3、FT4、FT3/FT4、TSH与克罗恩病维得利珠单抗治疗后临床活动度变化关系的研究

单位：1. 东南大学医学院, 江苏南京 210009;
2. 东南大学附属中大医院消化内科, 江苏南京 210009

关键词：克罗恩病维得利珠单抗临床应答游离三碘甲状腺原氨酸游离四碘甲状腺原氨酸游离三碘甲状腺原氨酸/游离四碘甲状腺原氨酸

分类号：R574

出版年·卷·期（页码）：2023·42·第六期（849-856）

摘要：

目的:探究血清游离三碘甲状腺原氨酸(FT3)、游离四碘甲状腺原氨酸(FT4)、FT3/FT4、促甲状腺激素(TSH)对克罗恩病(CD)患者维得利珠单抗(VDZ)治疗后临床应答的预测价值。方法:纳入2020年5月至2022年5月我院接受VDZ治疗且疗程超过3个月的CD患者54例,对照组89例。收集对照组及CD患者使用VDZ治疗前、治疗3个月后FT3、FT4、FT3/FT4、TSH等甲状腺功能指标数据,用CD活动指数(CDAI)评估CD疾病活动度。比较CD患者与对照组甲状腺功能指标差异。根据VDZ治疗前后CDAI差值(ΔCDAI)是否≥100分分为应答组及无应答组,比较两组患者VDZ治疗前后甲状腺功能指标变化及其差值(ΔFT3、ΔFT4、ΔFT3/FT4、ΔTSH)与ΔCDAI相关性;用受试者工作特征(ROC)曲线分析上述差值对VDZ临床应答的预测价值。结果:CD患者治疗前FT3、FT3/FT4低于对照组(P＜0.05);VDZ 治疗3个月后 FT3、FT3/FT4较前提高,FT4降低(P＜0.05)。应答组FT3、FT4、FT3/FT4、CDAI在VDZ治疗前后自身比较,差异均有统计学意义(P＜0.05)。VDZ治疗前后ΔFT3、ΔFT3/FT4与ΔCDAI间呈负相关(P＜0.05),ΔFT4、ΔTSH与ΔCDAI无直线相关关系(P＞0.05)。ΔFT3、ΔFT3/FT4预测VDZ治疗临床应答潜能的ROC曲线下面积(AUC)分别为0.837、0.827,灵敏度为82.9%、80.5%,特异度均为81.8%。结论:血清游离甲状腺功能指标变化尤其是FT3、FT3/FT4变化与CD患者VDZ治疗后临床活动指数变化呈负相关,并对其临床应答有一定预测价值。

Objective: To investigate the predictive value of serum free triiodothyronine(FT3), free tetraiodothyronine(FT4), FT3/FT4 and thyroid stimulating hormone(TSH) on clinical response to Vedolizumab(VDZ) in patients with Crohn's disease(CD). Methods: From May 2020 to May 2022, 54 patients with CD who received VDZ treatment for more than 3 months in our hospital and 89 healthy control cases(the control group) were included. FT3, FT4, FT3/FT4, TSH and other data of the control group and CD patients were collected before and 3 months after VDZ treatment. CD activity index(CDAI) was used to evaluate CD disease activity. The difference of thyroid function between CD group and the control group was compared. According to whether the difference of CDAI(ΔCDAI) before and after VDZ was more than 100 points, CD patients were divided into response group and non-response group. The changes of thyroid function indexes before and after VDZ treatment and the correlation between the differences(ΔFT3, ΔFT4, ΔFT3/FT4, ΔTSH) and ΔCDAI were compared between the two groups. The predictive value of the above difference to VDZ clinical response was analyzed by using receiver operating characteristic(ROC) curve. Results: Before treatment, FT3 and FT3/FT4 in CD patients were lower than those in the control group(P<0.05). After 3 months of VDZ treatment, FT3 and FT3/FT4 were increased, while FT4 was decreased(P<0.05). FT3, FT4, FT3/FT4 and CDAI in the response group were compared before and after VDZ treatment, and the differences were statistically significant(P<0.05). Before and after VDZ treatment, ΔFT3, ΔFT3/FT4 were negatively correlated with ΔCDAI(P<0.05), while there was no linear correlation between ΔFT4, ΔTSH and ΔCDAI(P>0.05). The area under curve(AUC) of ΔFT3 and ΔFT3/FT4 to predict the clinical response potential of VDZ treatment were 0.837 and 0.827, respectively, with sensitivity of 82.9% and 80.5% and specificity of 81.8%. Conclusion: The changes of serum free thyroid function indexes, especially FT3 and FT3/FT4, are negatively correlated with the changes of clinical activity index in CD patients after VDZ treatment, and have certain predictive value for clinical response.

参考文献：

[1] FAKHOURY M,NEGRULJ R,MOORANIAN A,et al.Inflammatory bowel disease:clinical aspects and treatments[J].Journal of Inflammation Research,2014,7:113.
[2] GREUTER T,VAVRICKA S R.Extraintestinal manifestations in inflammatory bowel disease-epidemiology,genetics,and pathogenesis[J].Expert Review of Gastroenterology & Hepatology,2019,13(4):307-317.
[3] KAPPELMAN M D,GALANKO J A,PORTER C Q,et al.Association of paediatric inflammatory bowel disease with other immune-mediated diseases[J].Arch Dis Child,2011,96(11):1042-1046.
[4] SONU I S,BLONSKI W,LIN M V,et al.Papillary thyroid cancer and inflammatory bowel disease:is there a relationship?[J].World J Gastroenterol,2013,19(7):1079-1084.
[5] PASCHOU S A,PALIOURA E,KOTHONAS F,et al.The effect of anti-TNF therapy on thyroid function in patients with inflammatory bowel disease[J].Endocr J,2018,65(11):1121-1125.
[6] LIN S,CHANCHLANI N,CARBERY I,et al.Understanding anti-TNF treatment failure:does serum triiodothyronine-to-thyroxine(T3/T4) ratio predict therapeutic outcome to anti-TNF therapies in biologic-naïve patients with active luminal Crohn's disease?[J].Aliment Pharmacol Ther,2022,56(5):783-793.
[7] 吴开春,梁洁,冉志华,等.炎症性肠病诊断与治疗的共识意见(2018年·北京)[J].中国实用内科杂志,2018,38(9):796-813.
[8] SATSANGI J,SILVERBERG M S,VERMEIRE S,et al.The Montreal classification of inflammatory bowel disease:controversies,consensus,and implications[J].Gut,2006,55(6):749-753.
[9] BEST W R,BECKTEL J M,SINGLETON J W,et al.Development of a Crohn's disease activity index.National Cooperative Crohn's Disease Study[J].Gastroenterology,1976,70(3):439-444.
[10] MONTESINOS M D M,PELLIZAS C G.Thyroid hormone action on innate immunity[J].Front Endocrinol(Lausanne),2019,10:350.
[11] DE VITO P,INCERPI S,PEDERSEN J Z,et al.Thyroid hormones as modulators of immune activities at the cellular level[J].Thyroid,2011,21(8):879-890.
[12] SHAHIN A A,MOSTAFA H,MAHMOUD S.Thyroid hormones and thyroid-stimulating hormone in Egyptian patients with systemic lupus erythematosus:correlation between secondary hypothyroidism and neuropsychiatric systemic lupus erythematosus syndromes[J].Mod Rheumatol,2002,12(4):338-341.
[13] BOELEN A,PLATVOET-TER SCHIPHORST M C,BAKKER O,et al.The role of cytokines in the lipopolysaccharide-induced sick euthyroid syndrome in mice[J].J Endocrinol,1995,146(3):475-483.
[14] BERTANI L,TRICÒ D,PUGLIESE D,et al.Serum triiodothyronine-to-thyroxine(T3/T4) ratio predicts therapeutic outcome to biological therapies in elderly IBD patients[J].Aliment Pharmacol Ther,2021,53(2):273-280.
[15] ORTIGA-CARVALHO T M,CHIAMOLERA M I,PAZOS-MOURA C C,et al.Hypothalamus-pituitary-thyroid axis[J].Compr Physiol,2016,6(3):1387-1428.
[16] NAKAMURA K,HONDA K,MIZUTANI T,et al.Novel strategies for the treatment of inflammatory bowel disease:selective inhibition of cytokines and adhesion molecules[J].World J Gastroenterol,2006,12(29):4628-4635.
[17] DANESE S.New therapies for inflammatory bowel disease:from the bench to the bedside[J].Gut,2012,61(6):918-932.
[18] PEYRIN-BIROULET L,DESREUMAUX P,SANDBORN W J,et al.Crohn's disease:beyond antagonists of tumour necrosis factor[J].Lancet,2008,372(9632):67-81.
[19] DANESE S,PANÉS J.Development of drugs to target interactions between leukocytes and endothelial cells and treatment algorithms for inflammatory bowel diseases[J].Gastroenterology,2014,147(5):981-989.
[20] MARAZUELA M,POSTIGO A A,ACEVEDO A,et al.Adhesion molecules from the LFA-1/ICAM-1,3 and VLA-4/VCAM-1 pathways on T lymphocytes and vascular endothelium in Graves' and Hashimoto's thyroid glands[J].Eur J Immunol,1994,24(10):2483-2490.
[21] JUBLANC C,BEAUDEUX J L,AUBART F,et al.Serum levels of adhesion molecules ICAM-1 and VCAM-1 and tissue inhibitor of metalloproteinases,TIMP-1,are elevated in patients with autoimmune thyroid disorders:relevance to vascular inflammation[J].Nutr Metab Cardiovasc Dis,2011,21(10):817-822.

服务与反馈：

【文章下载】【发表评论】【查看评论】【加入收藏】

提示：您还未登录，请登录！点此登录