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英夫利昔单抗不会使溃疡性结肠炎患者巨细胞病毒感染相关发作期间的病情恶化。

Infliximab Does Not Worsen Outcomes During Flare-ups Associated with Cytomegalovirus Infection in Patients with Ulcerative Colitis.

作者信息

Pillet Sylvie, Jarlot Camille, Courault Mathilde, Del Tedesco Emilie, Chardon Renaud, Saint-Sardos Pierre, Presles Emilie, Phelip Jean-Marc, Berthelot Philippe, Pozzetto Bruno, Roblin Xavier

机构信息

*EA-3064, Groupe Immunité des Muqueuses et Agents Pathogènes (GIMAP), Faculty of Medicine of Saint-Etienne, University of Lyon, Lyon, France; †Laboratory of Infectious Agents and Hygiene, University Hospital of Saint-Etienne, France; ‡Department of Gastroenterology, University Hospital of Saint-Etienne, France; and §Inserm, CIE3, F-42055 Saint-Etienne, France.

出版信息

Inflamm Bowel Dis. 2015 Jul;21(7):1580-6. doi: 10.1097/MIB.0000000000000412.

Abstract

BACKGROUND

Immunosuppressive therapies used for treating ulcerative colitis are known to favor chronic and latent viral diseases. This study aimed at evaluating prospectively the association between colonic cytomegalovirus (CMV) reactivation and anti-tumor necrosis factor (TNF) monoclonal antibodies (mabs) by comparison to azathioprine (AZA) in a series of flare-ups occurring in consecutive ulcerative colitis patients.

METHODS

A total of 109 flare-ups were recorded in 73 patients receiving a maintenance therapy by anti-TNF mabs (n = 69) or AZA (n = 40). The CMV DNA load in colonic tissue was determined by reverse transcription polymerase chain reaction on a pair of biopsies.

RESULTS

The number of CMV reactivation was of 35% and 38% in patients receiving anti-TNF mabs and AZA, respectively. The median of CMV DNA load was 378 [10-29,800] and 8300 [10-3,25,000] copies/mg of tissue in patients treated by anti-TNF mabs and AZA, respectively (P = 0.11 by Mann-Whitney U test). In a subgroup of 45 patients under anti-TNF mabs requiring an optimized treatment by infliximab, clinical remission (partial Mayo score <3) was not significantly impacted by the presence of CMV reactivation at the time of flare-up (P = 0.52). Twenty of these patients underwent a second colonic biopsy 8 weeks after the initiation of flare-up therapy; except for 3 patients, the colonic CMV DNA load was stable or decreased.

CONCLUSIONS

Patients under anti-TNF maintenance therapy are not at higher risk of CMV reactivation in case of flare-up. No reciprocal adverse influence was observed between anti-TNF mabs and CMV infection, suggesting that these drugs must be considered for treating flare-ups associated to CMV reactivation.

摘要

背景

已知用于治疗溃疡性结肠炎的免疫抑制疗法易引发慢性和潜伏性病毒疾病。本研究旨在通过比较硫唑嘌呤(AZA),前瞻性评估连续溃疡性结肠炎患者一系列病情发作中结肠巨细胞病毒(CMV)再激活与抗肿瘤坏死因子(TNF)单克隆抗体(mabs)之间的关联。

方法

73例接受抗TNF mabs(n = 69)或AZA(n = 40)维持治疗的患者共记录到109次病情发作。通过对一对活检组织进行逆转录聚合酶链反应测定结肠组织中的CMV DNA载量。

结果

接受抗TNF mabs和AZA治疗的患者中,CMV再激活的发生率分别为35%和38%。接受抗TNF mabs和AZA治疗的患者中,CMV DNA载量的中位数分别为378 [10 - 29,800]和8300 [10 - 325,000]拷贝/毫克组织(曼-惠特尼U检验,P = 0.11)。在45例需要英夫利昔单抗优化治疗的抗TNF mabs治疗患者亚组中,病情发作时CMV再激活的存在对临床缓解(部分梅奥评分<3)无显著影响(P = 0.52)。其中20例患者在病情发作治疗开始8周后进行了第二次结肠活检;除3例患者外,结肠CMV DNA载量稳定或下降。

结论

接受抗TNF维持治疗的患者在病情发作时CMV再激活风险并不更高。未观察到抗TNF mabs与CMV感染之间的相互不利影响,表明这些药物可用于治疗与CMV再激活相关的病情发作。

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