Leclerc Jacinthe, Blais Claudia, Rochette Louis, Hamel Denis, Guénette Line, Poirier Paul
From the Bureau d'Information en Santé des Populations, Institut national de santé publique du Québec (J.L., C.B., L.R., D.H.), Faculté de Pharmacie, Université Laval (J.L., C.B., L.G., P.P.), Department of Nursing, Université du Québec à Trois-Rivières (J.L.), Centre de recherche du CHU de Québec, Axe Santé des populations et pratiques optimales en santé (L.G.), and Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec (P.P.), Canada.
Circ Cardiovasc Qual Outcomes. 2017 Oct;10(10). doi: 10.1161/CIRCOUTCOMES.117.003891.
Once the patent of a brand-name drug expires, generic drugs are commercialized, and substitution from brand-name to generics may occur. Generic drug equivalence is evaluated through comparative bioavailability studies. Few studies have assessed outcomes after generic drug commercialization at a population level. We evaluated the impact of 3 generic angiotensin II receptor blockers commercialization on adverse events: hospitalizations or emergency room consultations.
This is an interrupted time series analysis using the Quebec Integrated Chronic Disease Surveillance System. Rates of adverse events for losartan, valsartan, and candesartan users (N=136 177) aged ≥66 years were calculated monthly, 24 months before and 12 months after generics commercialization. Periods before and after generics commercialization were compared by negative binomial segmented regression models. Sensitivity analyses were also conducted. For all users, there was a monthly mean rate of 100 adverse events for 1000 angiotensin II receptor blocker users before and after generic commercialization. Among generic users of losartan, valsartan, and candesartan, there was an increase in rates of adverse events of 8.0% (difference of proportions versus brand-name, 7.5% [95% confidence interval, -0.9% to 15.9%]; =0.0643), 11.7% (difference of proportions, 17.1% [95% confidence interval, 9.9%-24.3%]; <0.0001), and 14.0% (difference of proportions, 16.6% [95% confidence interval, 7.9%-25.3%]; <0.0001), respectively, the month of generic commercialization. The monthly trend of adverse events was affected for generic versus brand-name losartan users only (difference of proportions, 2.0% [0.7%-3.4%]; =0.0033) ≤1 year after generics commercialization. Similar results were found in sensitivity analyses.
Among generic users, immediate or delayed differences in adverse events rates were observed right after generic commercialization for 3 antihypertensive drugs. Rates of adverse events remained higher for generic users. Increases were more pronounced for generic candesartan, which is the studied product with the largest difference in comparative bioavailability. Risk and survival analysis studies controlling for several potential confounding factors are required to better characterize generic substitution.
一旦品牌药专利到期，仿制药就会商业化，可能会出现从品牌药向仿制药的替换。仿制药等效性通过比较生物利用度研究来评估。很少有研究在人群水平上评估仿制药商业化后的结果。我们评估了3种血管紧张素II受体阻滞剂仿制药商业化对不良事件（住院或急诊室就诊）的影响。
这是一项使用魁北克综合慢性病监测系统的中断时间序列分析。计算了年龄≥66岁的氯沙坦、缬沙坦和坎地沙坦使用者（N = 136177）在仿制药商业化前24个月和商业化后12个月每月的不良事件发生率。通过负二项式分段回归模型比较仿制药商业化前后的时间段。还进行了敏感性分析。对于所有使用者，仿制药商业化前后，每1000名血管紧张素II受体阻滞剂使用者每月的不良事件平均发生率为100次。在氯沙坦、缬沙坦和坎地沙坦的仿制药使用者中，仿制药商业化当月不良事件发生率分别增加了8.0%（与品牌药的比例差异为7.5% [95%置信区间，-0.9%至15.9%]；P = 0.0643）、11.7%（比例差异为17.1% [95%置信区间，9.9% - 24.3%]；P < 0.0001）和14.0%（比例差异为16.6% [95%置信区间，7.9% - 25.3%]；P < 报告中此处原文有误，推测为<0.0001）。仅在仿制药商业化后≤1年，氯沙坦仿制药与品牌药使用者的不良事件月度趋势受到影响（比例差异为2.0% [0.7% - 3.4%]；P = 0.0033）。敏感性分析中也发现了类似结果。
在仿制药使用者中，3种抗高血压药物仿制药商业化后立即或延迟出现了不良事件发生率的差异。仿制药使用者的不良事件发生率仍然较高。坎地沙坦仿制药的增加更为明显，它是比较生物利用度差异最大的研究产品。需要进行控制多个潜在混杂因素的风险和生存分析研究，以更好地描述仿制药替换情况。
