接受联合免疫调节剂治疗的儿科克罗恩病患者体内抗英夫利昔单抗抗体形成较少。

Less Anti-infliximab Antibody Formation in Paediatric Crohn Patients on Concomitant Immunomodulators.

作者信息

Kansen Hannah M, van Rheenen Patrick F, Houwen Roderick H J, Tjon A Ten Walther, Damen Gerard M, Kindermann Angelika, Escher Johanna C, Wolters Victorien M

机构信息

*Department of Paediatric Gastroenterology, University Medical Centre-Wilhelmina Children's Hospital, Utrecht†Department of Paediatric Gastroenterology, University Medical Centre Groningen, University of Groningen, Groningen‡Department of Paediatric Gastroenterology, Maxima Medical Centre, Veldhoven§Department of Paediatric Gastroenterology, Radboud University Medical Centre-Amalia Children's Hospital, Nijmegen||Department of Paediatric Gastroenterology, Emma Children's Hospital, Academic Medical Center, Amsterdam¶Department of Paediatric Gastroenterology, Erasmus Medical Centre-Sophia Children's Hospital, Rotterdam, The Netherlands.

出版信息

J Pediatr Gastroenterol Nutr. 2017 Oct;65(4):425-429. doi: 10.1097/MPG.0000000000001551.

DOI:10.1097/MPG.0000000000001551

PMID:28945207

Abstract

OBJECTIVES

To evaluate the effect of immunomodulators on formation of antibodies to infliximab (ATI) in paediatric patients with Crohn disease (CD) and the association of ATI and loss of response.

METHODS

Retrospective multicentre observational study (January 2009-December 2014) among Dutch children with CD treated with infliximab (IFX). ATI formation was analysed with Chi-square test and time-to-ATI formation with Kaplan-Meier and log-rank test.

RESULTS

A total of 229 children were identified. ATIs were measured in 162 patients (70.7%) and 25 (15%) developed ATIs: 6 of 62 (10%) on continuous combined immunosuppression (CCI), 11 of 81 (14%) on early combined immunosuppression (ECI), and 8 of 19 (42%) on IFX monotherapy. ATI formation was higher in patients on IFX monotherapy compared to CCI (P = 0.003) and ECI (P = 0.008), whereas no significant difference was found between CCI and ECI. Sixteen out of 25 patients (64%) with ATIs had loss of response, compared with 32 of 137 patients (19%) without ATIs (P < 0.00002, log rank 0.02). Among patients treated with ECI, 10 of 55 (18%) developed ATIs within the first 12 months, compared to 1 of 26 (4%) after more than 12 months.

CONCLUSIONS

In children with CD combination therapy is associated with significant reduction of antibody formation and prolonged effectivity compared to IFX monotherapy. ECI for at least 12 months, followed by IFX monotherapy, may be an equally effective alternative to CCI.

摘要

目的

评估免疫调节剂对克罗恩病（CD）患儿英夫利昔单抗抗体（ATI）形成的影响以及ATI与反应丧失之间的关联。

方法

对2009年1月至2014年12月间在荷兰接受英夫利昔单抗（IFX）治疗的CD患儿进行回顾性多中心观察研究。采用卡方检验分析ATI形成情况，采用Kaplan-Meier法和对数秩检验分析ATI形成时间。

结果

共纳入229名儿童。对162例患者（70.7%）检测了ATI，其中25例（15%）出现ATI：持续联合免疫抑制（CCI）组62例中有6例（10%），早期联合免疫抑制（ECI）组81例中有11例（14%），IFX单药治疗组19例中有8例（42%）。与CCI组（P = 0.003）和ECI组（P = 0.008）相比，IFX单药治疗组的ATI形成率更高，而CCI组和ECI组之间未发现显著差异。25例有ATI的患者中有16例（64%）出现反应丧失，而137例无ATI的患者中有32例（19%）出现反应丧失（P < 0.00002，对数秩0.02）。在接受ECI治疗的患者中，55例中有10例（18%）在最初12个月内出现ATI，而26例中有1例（4%）在12个月后出现。