Saniabadi Abbi R, Tanaka Tomotaka, Ohmori Toshihide, Sawada Koji, Yamamoto Takayuki, Hanai Hiroyuki
Abbi R Saniabadi, Department of Pharmacology, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan.
World J Gastroenterol. 2014 Aug 7;20(29):9699-715. doi: 10.3748/wjg.v20.i29.9699.
Ulcerative colitis and Crohn's disease are the major phenotypes of the idiopathic inflammatory bowel disease (IBD), which afflicts millions of individuals throughout the world with debilitating symptoms, impairing function and quality of life. Current medications are aimed at reducing the symptoms or suppressing exacerbations. However, patients require life-long medications, and this can lead to drug dependency, loss of response together with adverse side effects. Indeed, drug side effects become additional morbidity factor in many patients on long-term medications. Nonetheless, the efficacy of anti-tumour necrosis factors (TNF)-α biologics has validated the role of inflammatory cytokines notably TNF-α in the exacerbation of IBD. However, inflammatory cytokines are released by patients' own cellular elements including myeloid lineage leucocytes, which in patients with IBD are elevated with activation behaviour and prolonged survival. Accordingly, these leucocytes appear logical targets of therapy and can be depleted by adsorptive granulocyte/monocyte apheresis (GMA) with an Adacolumn. Based on this background, recently GMA has been applied to treat patients with IBD in Japan and in the European Union countries. Efficacy rates have been impressive as well as disappointing. In fact the clinical response to GMA seems to define the patients' disease course, response to medications, duration of active disease, and severity at entry. The best responders have been first episode cases (up to 100%) followed by steroid naïve and patients with a short duration of active disease prior to GMA. Patients with deep ulcers together with extensive loss of the mucosal tissue and cases with a long duration of IBD refractory to existing medications are not likely to benefit from GMA. It is clinically interesting that patients who respond to GMA have a good long-term disease course by avoiding drugs including corticosteroids in the early stage of their IBD. Additionally, GMA is very much favoured by patients for its good safety profile. GMA in 21st century reminds us of phlebotomy as a major medical practice at the time of Hippocrates. However, in patients with IBD, there is a scope for removing from the body the sources of pro-inflammatory cytokines and achieve disease remission. The bottom line is that by introducing GMA at an early stage following the onset of IBD or before patients develop extensive mucosal damage and become refractory to medications, many patients should respond to GMA and avoid pharmacologics. This should fulfill the desire to treat without drugs.
溃疡性结肠炎和克罗恩病是特发性炎症性肠病(IBD)的主要表型,全球数百万患者深受其害,症状令人虚弱,功能和生活质量受损。目前的药物旨在减轻症状或抑制病情加重。然而,患者需要终身服药,这可能导致药物依赖、疗效丧失以及不良反应。事实上,药物副作用在许多长期服药的患者中成为额外的发病因素。尽管如此,抗肿瘤坏死因子(TNF)-α生物制剂的疗效证实了炎性细胞因子尤其是TNF-α在IBD病情加重中的作用。然而,炎性细胞因子由患者自身的细胞成分释放,包括髓系白细胞,在IBD患者中,这些细胞因激活行为和生存期延长而增多。因此,这些白细胞似乎是合理的治疗靶点,可通过使用吸附柱进行吸附性粒细胞/单核细胞分离术(GMA)将其清除。基于这一背景,最近GMA已被应用于日本和欧盟国家的IBD患者治疗。有效率令人印象深刻,但也令人失望。事实上,对GMA的临床反应似乎决定了患者的病程、对药物的反应、活动期疾病的持续时间以及入院时的严重程度。最佳反应者是初发病例(高达100%),其次是未使用过类固醇的患者以及在GMA治疗前活动期疾病持续时间较短的患者。伴有深部溃疡以及广泛黏膜组织丧失的患者,以及对现有药物难治的病程较长的IBD病例不太可能从GMA中获益。临床上有趣的是,对GMA有反应的患者通过在IBD早期避免使用包括皮质类固醇在内的药物,有良好的长期病程。此外,GMA因其良好的安全性而深受患者青睐。21世纪的GMA让我们想起了希波克拉底时代作为主要医疗手段的放血疗法。然而,对于IBD患者,有机会从体内清除促炎细胞因子的来源并实现疾病缓解。关键在于,在IBD发病后早期或在患者出现广泛黏膜损伤并对药物难治之前引入GMA,许多患者应该会对GMA有反应并避免使用药物。这应该能够满足无药治疗的愿望。