Schattenkirchner M, Missler B, Mulz D
Scand J Rheumatol Suppl. 1986;63:57-66.
Data about adverse events can be particularly useful when assessing newly marketed drugs. However, spontaneous reporting of adverse events does not generally provide sufficient or highly accurate data on incidence and prevalence. In order to provide the most complete and accurate data, a postmarketing surveillance program (PMSP) for auranofin (AF) oral gold therapy for rheumatoid arthritis (RA) was conducted in the Federal Republic of Germany (FRG) from December 1982 through December 1985. The objectives of the program were to observe a large population treated with AF for more than a year; to compare the safety profile of AF with experience from clinical trials; and to register rare or previously unknown adverse events. The program included 2,777 patients with RA from 928 test centers. Disease duration was less than 2 years in 29%. 2-5 in 23.2%, 5-10 in 32.5%, and more than 10 in 13.3% (no data for 2%); disease was mild or moderate in 67.4% and severe in 29.9% (no data for 2.7%). Auranofin was given 6 mg/day as either two 3-mg tablets at breakfast or 1 tablet at breakfast and 1 at the evening meal. Laboratory studies and efficacy, as indicated by increase in grip strength and decrease in number of tender and swollen joints, were monitored regularly. A total of 1,595 patients completed 1 year of treatment with AF. Withdrawals included 12.9% for adverse events, 4.2% for insufficient therapeutic effect, and 33.1% for a variety of administrative or technical reasons. The most common adverse event was alteration in stool pattern, which occurred in 22.5% of patients, compared with 46.6% in worldwide AF clinical trials. Other gastrointestinal symptoms occurred in 17.4%, compared with 22.4% worldwide. The occurrence of most adverse events in the PMSP was much less than in worldwide studies, for example: skin rash 7.3% vs. 24.2% worldwide, pruritus 4.2% vs. 16.6%, proteinuria 1.0% vs. 5.0%, and leukopenia 0.7% vs. 1.9%. These discrepancies may be explained by the method of monitoring employed in the postmarketing study, which favored the reporting of only clinically relevant adverse events. The pattern of occurrence of adverse events was similar to that seen during other AF trials, indicating that any intolerance to AF occurs primarily within the first 6 months of treatment. However, hematologic or nephrologic adverse events appear to be independent of time on therapy, with a constant monthly prevalence of about 0.1-0.2%.(ABSTRACT TRUNCATED AT 400 WORDS)
在评估新上市药物时，不良事件的数据可能特别有用。然而，不良事件的自发报告通常无法提供关于发病率和患病率的充分或高度准确的数据。为了提供最完整和准确的数据，1982年12月至1985年12月在德意志联邦共和国（FRG）开展了一项针对用于类风湿性关节炎（RA）的金诺芬（AF）口服金疗法的上市后监测计划（PMSP）。该计划的目标是观察大量接受AF治疗超过一年的人群；将AF的安全性概况与临床试验经验进行比较；并记录罕见或以前未知的不良事件。该计划纳入了来自928个测试中心的2777例RA患者。病程小于2年的占29%，2 - 5年的占23.2%，5 - 10年的占32.5%，超过10年的占13.3%（2%无数据）；疾病为轻度或中度的占67.4%，重度的占29.9%（2.7%无数据）。金诺芬的给药剂量为每日6毫克，早餐时服用两片3毫克片剂，或早餐时服用1片，晚餐时服用1片。定期监测实验室检查以及疗效，疗效通过握力增加和压痛及肿胀关节数量减少来体现。共有1595例患者完成了1年的AF治疗。因不良事件停药的占12.9%，因治疗效果不佳停药的占4.2%，因各种管理或技术原因停药的占33.1%。最常见的不良事件是大便习惯改变，22.5%的患者出现该情况，而在全球AF临床试验中这一比例为46.6%。其他胃肠道症状的发生率为17.4%，全球范围内为22.4%。PMSP中大多数不良事件的发生率远低于全球研究，例如：皮疹7.3%对全球24.2%，瘙痒4.2%对16.6%，蛋白尿1.0%对5.0%，白细胞减少0.7%对1.9%。这些差异可能是由于上市后研究中采用的监测方法造成的，该方法更倾向于仅报告临床相关的不良事件。不良事件的发生模式与其他AF试验中观察到的相似，表明对AF的任何不耐受主要发生在治疗的前6个月内。然而，血液学或肾脏不良事件似乎与治疗时间无关，每月患病率恒定在约0.1 - 0.2%。（摘要截选至40词）
