Shen Bo, Pardi Darrell S, Bennett Ana E, Queener Elaine, Kammer Patricia, Hammel Jefferey P, LaPlaca Caroline, Harris M Scott
Pouchitis Clinic, Digestive Disease Institute, The Cleveland Clinic Foundation, 9500 Euclid Ave., Cleveland, OH 44195, USA.
Am J Gastroenterol. 2009 Jun;104(6):1468-74. doi: 10.1038/ajg.2009.138.
Although a majority of patients with pouchitis respond favorably to antibiotic therapy, many relapse frequently, and nonabsorbable and non-antibiotic-based agents are desirable for reducing bacterial resistance and the systemic adverse effects associated with long-term antibiotic exposure. AST-120 (a spherical carbon adsorbent) comprises highly adsorptive, porous carbon microspheres with the ability to adsorb small-molecular-weight toxins, inflammatory mediators,and harmful bile acids. The aim of this pilot trial was to evaluate the efficacy and tolerability of AST-120 in the treatment of active pouchitis.
Eligible patients were recruited from two subspecialty pouchitis clinics. Inclusion criteria were(i) ileal pouch-anal anastomosis performed for ulcerative colitis; (ii) active pouchitis with Pouchitis Disease Activity Index (PDAI) scores > or =7; and (iii) discontinuation of antibiotic therapy for at least 2 weeks. Exclusion criteria included Crohn's disease of the pouch, isolated cuffitis, pouch strictures, abscess, and sinuses. All eligible patients received AST-120 in 2-g sachets (oral) open label, thrice a day for 4 weeks. The primary efficacy end point was remission as defined by a PDAI score of < 7 points; the main secondary end point was clinical response, defined by a reduction of the PDAI score of > or =3 points.
Nineteen of 20 patients completed the trial. Eleven patients (55.0 % ) had a clinical response to the therapy and 10 patients (50.0 % ) entered remission. Median reduction in the PDAI symptom, endoscopy, and histology subscores, and PDAI total scores after 4 weeks were -2( P = 0.002), -2 ( P = 0.003), 0 ( P = 0.32), and -4 ( P = 0.001) points, respectively. The agent was well tolerated; one patient experienced transient mild elevation of alkaline phosphatase of uncertain significance and one patient experienced an upper respiratory infection after taking one dose of AST-120 and was excluded from the fi nal analysis for the calculation of pre- and post-trial PDAI scores.
AST-120 seems to be effective and well tolerated in treating patients with active pouchitis.A randomized, placebo-controlled trial is warranted for assessing the long-term efficacy and safety of AST-120 in the disease.
虽然大多数袋炎患者对抗生素治疗反应良好，但许多患者频繁复发，因此需要使用不可吸收且非抗生素类药物来降低细菌耐药性以及长期使用抗生素带来的全身不良反应。AST - 120（一种球形碳吸附剂）由具有高吸附性的多孔碳微球组成，能够吸附小分子毒素、炎症介质和有害胆汁酸。这项试点试验的目的是评估AST - 120治疗活动性袋炎的疗效和耐受性。
符合条件的患者从两家袋炎专科诊所招募。纳入标准为：（i）因溃疡性结肠炎行回肠袋肛管吻合术；（ii）活动性袋炎，袋炎疾病活动指数（PDAI）评分≥7；（iii）停用抗生素治疗至少2周。排除标准包括袋的克罗恩病、孤立性袖口炎、袋狭窄、脓肿和窦道。所有符合条件的患者接受2克袋装的AST - 120（口服，开放标签），每日3次，共4周。主要疗效终点为PDAI评分<7分定义的缓解；主要次要终点为临床反应，定义为PDAI评分降低≥3分。
20例患者中有19例完成试验。11例患者（55.0%）对治疗有临床反应，10例患者（50.0%）进入缓解期。4周后，PDAI症状、内镜检查和组织学亚评分以及PDAI总分的中位数降低分别为-2（P = 0.002）、-2（P = 0.003）、0（P = 0.32）和-4（P = 0.001）分。该药物耐受性良好；1例患者碱性磷酸酶出现短暂轻度升高，意义不明，1例患者服用一剂AST - 120后出现上呼吸道感染，在计算试验前后PDAI评分的最终分析中被排除。
AST - 120在治疗活动性袋炎患者中似乎有效且耐受性良好。有必要进行一项随机、安慰剂对照试验来评估AST - 120在该疾病中的长期疗效和安全性。
