Overtreatment of COPD with Inhaled Corticosteroids - Implications for Safety and Costs: Cross-Sectional Observational Study

Introduction
Combined inhaled long-acting beta-agonists and corticosteroids (LABA+ICS) are costly. They are recommended in severe or very severe chronic obstructive pulmonary disease (COPD). They should not be prescribed in mild or moderate disease. In COPD ICS are associated with side-effects including risk of pneumonia. We quantified appropriateness of prescribing and examined the risks and costs associated with overuse.
Methods
Data were extracted from the electronic and paper records of 41 London general practices (population 310,775) including spirometry, medications and exacerbations. We classified severity, assessed appropriateness of prescribing using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines for 2009, and performed a sensitivity analysis using the broader recommendations of the 2011 revision.
Results
3537 patients had a diagnosis of COPD. Spirometry was recorded for 2458(69%). 709(29%) did not meet GOLD criteria. 1749(49%) with confirmed COPD were analysed: 8.6% under-treated, 38% over-treated. Over-prescription of ICS in GOLD stage I or II (n=403, 38%) and in GOLD III or IV without exacerbations (n=231, 33.6%) was common. An estimated 12 cases (95%CI 7-19) annually of serious pneumonia were likely among 897 inappropriately treated. 535 cases of overtreatment involved LABA+ICS with a mean per patient cost of £553.56/year (€650.03). Using the broader indications for ICS in the 2011 revised GOLD guideline 25% were still classified as over-treated. The estimated risk of 15 cases of pneumonia (95%CI 8-22) in 1074 patients currently receiving ICS would rise by 20% to 18 (95%CI 9.8-26.7) in 1305 patients prescribed ICS if all with GOLD grade 3 and 4 received LABA+ICS.
Conclusion
Over-prescription of ICS in confirmed COPD was widespread with considerable potential for harm. In COPD where treatment is often escalated in the hope of easing the burden of disease clinicians should consider both the risks and benefits of treatment and the costs where the benefits are unproven.

引言

吸入用长效β₂受体激动剂联合糖皮质激素（long-acting beta-agonists and corticosteroids, LABA+ICS）治疗成本高昂。该联合疗法仅被推荐用于重度或极重度慢性阻塞性肺疾病（chronic obstructive pulmonary disease, COPD）患者，禁用于轻中度慢阻肺患者。慢阻肺患者使用吸入性糖皮质激素（inhaled corticosteroids, ICS）会伴随包括肺炎风险在内的多种不良反应。本研究量化了处方合理性，并分析了过度使用该疗法带来的风险与经济成本。

方法

研究数据提取自伦敦41家全科诊所的电子与纸质病历，覆盖人口310775人，包含肺功能检查、用药记录及急性加重事件信息。本研究对患者病情严重程度进行分级，依据2009版慢性阻塞性肺疾病全球倡议（Global Initiative for Chronic Obstructive Lung Disease, GOLD）指南评估处方合理性，并采用2011版修订指南的宽泛推荐标准进行敏感性分析。

结果

共计3537名患者被确诊为慢阻肺，其中2458例（69%）留存肺功能检查记录，709例（29%）不符合GOLD诊断标准。最终纳入1749例（49%）确诊慢阻肺患者进行分析：8.6%治疗不足，38%治疗过度。GOLD 1级或2级患者（n=403，38%）以及无急性加重的GOLD 3级或4级患者（n=231，33.6%）中，糖皮质激素过度处方现象普遍。在897例接受不当治疗的患者中，每年预计会发生12例（95%置信区间7-19）重症肺炎。535例过度治疗患者使用了LABA+ICS疗法，人均年治疗成本为553.56英镑（折合650.03欧元）。即便采用2011版GOLD修订指南中糖皮质激素的宽泛适应症标准，仍有25%的患者被判定为过度治疗。若所有GOLD 3级和4级患者均使用LABA+ICS疗法，当前接受ICS治疗的1074例患者中预计发生15例肺炎（95%置信区间8-22），而在1305例处方ICS的患者中，肺炎病例数将增加20%至18例（95%置信区间9.8-26.7）。

结论

确诊慢阻肺患者中糖皮质激素过度处方现象普遍，存在显著健康损害风险。慢阻肺治疗常为缓解疾病负担而逐步升级，临床医生在治疗获益尚未明确的情况下，应综合权衡治疗的风险、获益与经济成本。