Layton D, Heeley E, Hughes K, Shakir S A W
Drug Safety Research Unit, Bursledon Hall, Blundell Lane, Southampton, UK.
Rheumatology (Oxford). 2003 May;42(5):622-31. doi: 10.1093/rheumatology/keg141.
and objectives. Non-steroidal anti-inflammatory drugs (NSAIDs) are associated with gastrointestinal (GI) toxicity. Rofecoxib and meloxicam are classified as cyclooxygenase (COX)-2 selective inhibitors. The Drug Safety Research Unit monitored the safety of these drugs immediately after their launch in England using the non-interventional observational cohort technique of prescription-event monitoring (PEM). Our objective was to investigate whether there is a clinically relevant difference in the incidence of reported symptomatic (acid/peptic) and complicated upper GI conditions (perforations/bleeding) between rofecoxib and meloxicam during use in general practice.
Patients were identified from dispensed prescriptions written by general practitioners (GPs) for meloxicam (between December 1996 and March 1997) and rofecoxib (between July and November 1999). Simple questionnaires requesting details of events occurring during/after treatment and potential risk factors (including age, sex, history of upper GI problems, and NSAIDS prescribed within 3 months of treatment) were posted to prescribing GPs approximately 9 months after the first prescription for each patient. Incidence rates of the first event were calculated, and crude and adjusted rate ratios were obtained using regression modelling.
For rofecoxib and meloxicam respectively, 1127 (7.4%) and 1376 (7.2%) patients had symptomatic (acid/peptic) upper GI events, whereas 57 (0.4%) and 67 (0.4%) had complicated upper GI conditions (perforations/bleeding). A past medical history of upper GI problems was an important risk factor only for symptomatic (acid/peptic) upper GI events for both drugs, despite a two-fold difference in the proportion reporting previous GI problems (48.4 and 25.1% for rofecoxib and meloxicam respectively). The adjusted rate ratio of symptomatic (acid/peptic) upper GI events or complicated upper GI conditions (perforations/bleeding) for rofecoxib compared with meloxicam was 0.71 (95% confidence interval 0.65, 0.79) and 0.91 (95% confidence interval 0.59, 1.42) respectively.
This study reports a relative reduction (29%) in the incidence rate of symptomatic (acid/peptic) GI events, and no difference in the incidence rate of complicated upper GI conditions (perforations/bleeding) for rofecoxib compared with meloxicam.
背景与目的。非甾体抗炎药（NSAIDs）与胃肠道（GI）毒性相关。罗非昔布和美洛昔康被归类为环氧化酶（COX）-2选择性抑制剂。药物安全研究单位在罗非昔布和美洛昔康于英国上市后，立即采用处方事件监测（PEM）这种非干预性观察队列技术对这些药物的安全性进行监测。我们的目的是调查在全科医疗使用过程中，罗非昔布和美洛昔康在报告的有症状（酸/消化性）和复杂性上消化道疾病（穿孔/出血）的发生率方面是否存在临床相关差异。
方法。从全科医生（GPs）开出的美洛昔康（1996年12月至1997年3月）和罗非昔布（1999年7月至11月）的配药处方中识别患者。在为每位患者开出第一张处方约9个月后，向开处方的全科医生发送简单问卷，询问治疗期间/之后发生的事件细节以及潜在风险因素（包括年龄、性别、上消化道问题病史以及治疗前3个月内开具的非甾体抗炎药）。计算首次事件的发生率，并使用回归模型获得粗率比和调整率比。
结果。罗非昔布和美洛昔康分别有1127名（7.4%）和1376名（7.2%）患者发生有症状（酸/消化性）上消化道事件，而有57名（0.4%）和67名（0.4%）患者发生复杂性上消化道疾病（穿孔/出血）。上消化道问题的既往病史仅是两种药物有症状（酸/消化性）上消化道事件的重要风险因素，尽管报告既往胃肠道问题的比例存在两倍差异（罗非昔布和美洛昔康分别为48.4%和25.1%）。与美洛昔康相比，罗非昔布有症状（酸/消化性）上消化道事件或复杂性上消化道疾病（穿孔/出血）的调整率比分别为0.71（95%置信区间0.65，0.79）和0.91（95%置信区间0.59，1.42）。
结论。本研究报告，与美洛昔康相比，罗非昔布有症状（酸/消化性）胃肠道事件的发生率相对降低（29%），而复杂性上消化道疾病（穿孔/出血）的发生率无差异。
