Incidence of ischemic colitis and serious complications of constipation among patients using alosetron: Systematic review of clinical trials and post-marketing surveillance data
Incidence of ischemic colitis and serious complications of constipation among patients using alosetron: Systematic review of clinical trials and post-marketing surveillance data
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DOI：
10.1111/j.1572-0241.2006.00459.x
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发表时间：
2006-05-01
影响因子：
9.8
通讯作者：
Schoenfeld, Philip
中科院分区：
文献类型：
--
作者：
Chang, Lin;Chey, William D.;Schoenfeld, Philip
背景技术背景：据报道，缺血性结肠炎和严重的便秘并发症与使用阿洛司琼有关，阿洛司琼被批准用于常规治疗失败的重度腹泻为主的IBS女性。本系统评价计算了这些不良事件的发生率在阿洛司琼使用患者的临床试验和上市后surveillance.METHODS：专家小组在流行病学和功能性肠病审查临床试验报告表和FDA MedWatch形式的每一个报告的缺血性结肠炎或严重并发症的便秘。专家对患者使用阿洛司琼还是安慰剂不知情。使用预先规定的标准，专家们评估了准确诊断的可能性以及药物使用和不良事件之间的关联。与报告的诊断不一致或与药物使用不可能相关的病例从不良事件发生率的计算中剔除。来自临床试验的汇总数据表明，与使用安慰剂的患者相比，使用阿洛司琼的患者缺血性结肠炎的发生率增加（分别为0.15%和0.0%，p = 0.03），但便秘严重并发症的发生率无显著差异。所有（19/19）使用阿洛司琼的缺血性结肠炎患者均发生可逆性结肠炎，无长期后遗症。基于上市后监测数据，缺血性结肠炎的后裁定率为1.1每1,000患者-年的阿洛司琼使用和便秘的严重并发症的发生率为0.66每1,000患者-年的阿洛司琼use.CONCLUSION：缺血性结肠炎和便秘的严重并发症的发生率是非常低的，很少与长期后遗症或严重的发病率。
BACKGROUND: Ischemic colitis and serious complications of constipation have been reported in association with the use of alosetron, which is approved for women with severe diarrhea-predominant IBS who have failed conventional therapies. This systematic review calculated the incidence of these adverse events in alosetron-using patients in clinical trials and post-marketing surveillance.METHODS: A panel of experts in epidemiology and functional bowel disorders reviewed clinical trial report forms and FDA MedWatch forms of each reported case of ischemic colitis or serious complications of constipation. Experts were blinded about whether patients used alosetron or placebo. Using pre-specified criteria, experts rated the likelihood of an accurate diagnosis and an association between medication use and adverse events. Cases that were not consistent with the reported diagnosis or not possibly associated with medication use were eliminated from calculation of incidence rates of adverse events.RESULTS: Pooled data from clinical trials indicate an increased rate of ischemic colitis among alosetron-using patients compared to placebo-using patients (0.15% vs 0.0%, respectively, p = 0.03), but there was no significant difference in the rate of serious complications of constipation. All (19/19) alosetron-using patients with ischemic colitis had reversible colitis without long-term sequelae. Based on post-marketing surveillance data, the post-adjudication rate of ischemic colitis is 1.1 per 1,000 patient-years of alosetron use and the rate of serious complications of constipation is 0.66 per 1,000 patient-years of alosetron use.CONCLUSION: The incidence of ischemic colitis and serious complications of constipation is very low and is rarely associated with long-term sequelae or serious morbidity.