Oh Eun Hye, Oh Kyunghwan, Han Minkyu, Seo Hyungil, Chang Kiju, Lee Sun-Ho, Kim Gwang-Un, Song Eun Mi, Seo Myeongsook, Lee Ho-Su, Hwang Sung Wook, Park Sang Hyoung, Yang Dong-Hoon, Kim Kyung-Jo, Byeon Jeong-Sik, Myung Seung-Jae, Yang Suk-Kyun, Ye Byong Duk
Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
Department of Clinical Epidemiology and Biostatistics, University of Ulsan College of Medicine, Seoul, Korea.
PLoS One. 2017 May 23;12(5):e0177479. doi: 10.1371/journal.pone.0177479. eCollection 2017.
Although early treatment of Crohn's disease (CD) patients with anti-tumor necrosis factor (TNF) agents or immunomodulators (IMs) may improve long-term outcomes, especially those with poor prognostic factors, their effectiveness in Asians remains unclear. In this study, Korean patients with CD naïve to both intestinal surgery and intestinal complications, and with at least two risk factors for progression (diagnosis at age <40 years, systemic corticosteroid treatment <3 months after diagnosis, and perianal fistula at diagnosis) were retrospectively analyzed. Patients were classified into those who started anti-TNFs, or IMs but not anti-TNFs, within 2 years of diagnosis, and those who started anti-TNFs and/or IMs later. Their probabilities of intestinal surgery and intestinal complications were compared. A total of 670 patients were enrolled, 79 in the early anti-TNF, 286 in the early IM, and 305 in the late treatment group. Kaplan-Meier analysis with the log-rank test showed that from starting anti-TNFs/IMs, times to intestinal surgery (P < 0.001), stricturing complications (P = 0.002), and penetrating complications (P < 0.001) were significantly longer in the early anti-TNF/IM groups than in the late treatment group. Multivariate Cox regression analysis showed that, from starting anti-TNFs/IMs, late anti-TNF/IM treatment was independently associated with higher risks of intestinal surgery (adjusted hazard ratio [aHR] 2.321, 95% confidence interval [CI] 1.503-3.584, P < 0.001), behavioral progression (aHR 2.001, 95% CI 1.449-2.763, P < 0.001), stricturing complications (aHR 1.736, 95% CI 1.209-2.493, P = 0.003), and penetrating complications (aHR 3.315, 95% CI 2.094-5.249, P < 0.001) than early treatment. In conclusion, treatment of Asian CD patients having poor prognostic factors with anti-TNFs/IMs within 2 years of diagnosis is associated with better clinical outcomes than later treatment.
尽管使用抗肿瘤坏死因子（TNF）药物或免疫调节剂（IMs）对克罗恩病（CD）患者进行早期治疗可能会改善长期预后，尤其是那些具有不良预后因素的患者，但其在亚洲人中的有效性仍不明确。在本研究中，对韩国CD患者进行了回顾性分析，这些患者未接受过肠道手术和肠道并发症治疗，且至少有两个疾病进展风险因素（诊断时年龄<40岁、诊断后<3个月接受全身皮质类固醇治疗、诊断时存在肛周瘘管）。患者被分为在诊断后2年内开始使用抗TNF药物或IMs但未使用抗TNF药物的患者，以及之后开始使用抗TNF药物和/或IMs的患者。比较了他们发生肠道手术和肠道并发症的概率。共纳入670例患者，79例接受早期抗TNF治疗，286例接受早期IM治疗，305例接受晚期治疗。采用对数秩检验的Kaplan-Meier分析表明，从开始使用抗TNF药物/IMs起，早期抗TNF/IM组发生肠道手术的时间（P<0.001）、狭窄并发症的时间（P = 0.002）和穿透性并发症的时间（P<0.001）均显著长于晚期治疗组。多变量Cox回归分析表明，从开始使用抗TNF药物/IMs起，晚期抗TNF/IM治疗与肠道手术风险较高独立相关（调整后风险比[aHR] 2.321，95%置信区间[CI] 1.503 - 3.584，P<0.001）、行为进展风险较高（aHR 2.001，95% CI 1.449 - 2.763，P<0.001）、狭窄并发症风险较高（aHR 1.736，95% CI 1.209 - 2.493，P = 0.003）以及穿透性并发症风险较高（aHR 3.315，95% CI 2.094 - 5.249，P<0.001）。总之，对具有不良预后因素的亚洲CD患者在诊断后2年内使用抗TNF药物/IMs进行治疗，与晚期治疗相比，临床结局更好。
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