肿瘤坏死因子拮抗剂对原发性硬化性胆管炎患者的影响。
Effects of Tumor Necrosis Factor Antagonists in Patients With Primary Sclerosing Cholangitis.
作者信息
Hedin Charlotte Rose Hawkey, Sado Gina, Ndegwa Nelson, Lytvyak Ellina, Mason Andrew, Montano-Loza Aldo, Gerussi Alessio, Saffioti Francesca, Thorburn Douglas, Nilsson Emma, Larsson Geir, Moum Bjørn A, van Munster Kim N, Ponsioen Cyriel Y, Levy Cynthia, Nogueira Nicholas F, Bowlus Christopher L, Gotlieb Neta, Shibolet Oren, Lynch Kate D, Chapman Roger W, Rupp Christian, Vesterhus Mette, Jørgensen Kristin K, Rorsman Fredrik, Schramm Christoph, Sabino João, Vermeire Severine, Zago Alessandra, Cazzagon Nora, Marschall Hanns-Ulrich, Ytting Henriette, Ben Belkacem Karima, Chazouilleres Olivier, Almer Sven, Bergquist Annika
机构信息
Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Division of Gastroenterology, Medical Unit Gastroenterology, Dermatovenereology and Rheumatology, Karolinska University Hospital, Stockholm, Sweden; European Reference Network on Hepatological Diseases.
Department of Gastroenterology and Hepatology, Karolinska University Hospital, Stockholm, Sweden; European Reference Network on Hepatological Diseases.
出版信息
Clin Gastroenterol Hepatol. 2020 Sep;18(10):2295-2304.e2. doi: 10.1016/j.cgh.2020.02.014. Epub 2020 Feb 15.
BACKGROUND & AIMS: Few patients with primary sclerosing cholangitis (PSC) and inflammatory bowel diseases (IBDs) are exposed to tumor necrosis factor (TNF) antagonists because of the often mild symptoms of IBD. We assessed the effects of anti-TNF agents on liver function in patients with PSC and IBD, and their efficacy in treatment of IBD.
METHODS
We performed a retrospective analysis of 141 patients with PSC and IBD receiving treatment with anti-TNF agents (infliximab or adalimumab) at 20 sites (mostly tertiary-care centers) in Europe and North America. We collected data on the serum level of alkaline phosphatase (ALP). IBD response was defined as either endoscopic response or, if no endoscopic data were available, clinical response, as determined by the treating clinician or measurements of fecal calprotectin. Remission was defined more stringently as endoscopic mucosal healing. We used linear regression analysis to identify factors associated significantly with level of ALP during anti-TNF therapy.
RESULTS
Anti-TNF treatment produced a response of IBD in 48% of patients and remission of IBD in 23%. There was no difference in PSC symptom frequency before or after drug exposure. The most common reasons for anti-TNF discontinuation were primary nonresponse of IBD (17%) and side effects (18%). At 3 months, infliximab-treated patients had a median reduction in serum level of ALP of 4% (interquartile range, reduction of 25% to increase of 19%) compared with a median 15% reduction in ALP in adalimumab-treated patients (interquartile range, reduction of 29% to reduction of 4%; P = .035). Factors associated with lower ALP were normal ALP at baseline (P < .01), treatment with adalimumab (P = .090), and treatment in Europe (P = .083).
CONCLUSIONS
In a retrospective analysis of 141 patients with PSC and IBD, anti-TNF agents were moderately effective and were not associated with exacerbation of PSC symptoms or specific side effects. Prospective studies are needed to investigate the association between use of adalimumab and reduced serum levels of ALP further.
背景与目的
由于炎症性肠病（IBD）症状通常较轻，很少有原发性硬化性胆管炎（PSC）合并IBD的患者使用肿瘤坏死因子（TNF）拮抗剂。我们评估了抗TNF药物对PSC合并IBD患者肝功能的影响及其治疗IBD的疗效。
方法
我们对欧洲和北美的20个地点（大多为三级医疗中心）接受抗TNF药物（英夫利昔单抗或阿达木单抗）治疗的141例PSC合并IBD患者进行了回顾性分析。我们收集了碱性磷酸酶（ALP）血清水平的数据。IBD反应定义为内镜反应，或者如果没有内镜数据，则为由治疗医生确定的临床反应或粪便钙卫蛋白测量值。缓解更严格地定义为内镜下黏膜愈合。我们使用线性回归分析来确定与抗TNF治疗期间ALP水平显著相关的因素。
结果
抗TNF治疗使48%的患者IBD有反应，23%的患者IBD缓解。药物暴露前后PSC症状频率无差异。抗TNF停药的最常见原因是IBD原发性无反应（17%）和副作用（18%）。在3个月时，英夫利昔单抗治疗的患者血清ALP水平中位数降低4%（四分位间距，降低25%至升高19%），而阿达木单抗治疗的患者ALP中位数降低15%（四分位间距，降低29%至降低4%；P = 0.035）。与较低ALP相关的因素是基线时ALP正常（P < 0.01）、使用阿达木单抗治疗（P = 0.090）和在欧洲治疗（P = 0.083）。
结论
在对141例PSC合并IBD患者的回顾性分析中，抗TNF药物有中等疗效，且与PSC症状加重或特定副作用无关。需要进行前瞻性研究以进一步调查阿达木单抗的使用与血清ALP水平降低之间的关联。
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