類別:

高風險藥物與急性住院：病例─時間─對照研究

2021-06-16T02:38:03Z

標題: 高風險藥物與急性住院：病例─時間─對照研究; High-Risk Medications and Emergency Hospitalizations: A Case–Time–Control Study 作者: Chih-Wan Lin; 林芝琬摘要: 研究背景藥物不良事件會惡化病人的健康情況，也會為有限的醫療資源帶來沉重的負擔，若能有效率地找出可能導致嚴重藥物不良事件(如：藥物不良事件引起之住院)的高風險藥物，將有助臨床工作者與政策制定者針對此議題進行改善。過去研究探討不同藥物相關之住院風險此一議題時，多採用分析自動通報紀錄、病歷回顧、以及從病歷資料庫中篩選藥物不良反應相關之診斷碼等方式進行，然而這些方式普遍存在通報不足的問題且各個藥物不良反應之特性會影響通報率；此外，多數研究僅呈現藥物引起之住院事件數而未考慮藥物在整體族群之使用盛行率。研究目的為解決上述的研究限制，本研究使用臺灣全民健康保險研究資料庫為資料來源，以病例─時間─對照設計 (case–time–control design) 探討高風險藥物和急性住院事件之間的相關性。研究方法由2000年承保抽樣歸人檔中選取年滿20歲且2000年1月1日至2011年12月31日至少有一筆門診處方紀錄者為研究族群。於研究族群中篩選出急性住院事件為index visits而門診就醫事件為reference visits，並將index visits與reference visits以性別、年齡、index date (定義為index 及reference visits 的首日)、Charlson Comorbidity Index、門診次數進行1:1配對。Index visits與reference visits之病例期定為index date 前1-14天，對照期則定為index date 前366-379天，再比較高風險藥物分別在病例期與對照期之暴露情形，本研究選定的高風險藥物為diabetic agents、diuretics、nonsteroidal anti-inflammatory drugs (NSAIDs)、anticoagulants、antiplatelets、antihypertensives、 antiarrhythmics、anticonvulsants、antipsychotics、antidepressants、benzodiazepine (BZD)/Z-hypnotics以及narcotics。統計分析使用條件式邏輯迴歸模型進行odds ratio (OR)的預測，並校正隨時間改變之干擾因子 (包含病例期和對照期之Charlson Comorbidity Index、門診就診次數、急診就診次數、慢性用藥總數)，另計算急性住院事件中與高風險藥物相關之可歸因風險 (attributable fraction (AF))。研究結果於12種本研究選定的高風險藥物中，急性住院風險顯著增加者有7種，風險高至低依序為antipsychotics (adjusted OR: 1.54, 95% confidence interval [1.37-1.73], AF: 35.0%)、NSAIDs (1.50, [1.44-1.56], 33.3%)、anticonvulsants (1.34, [1.10-1.64], 25.6%)、diuretics (1.24, [1.15-1.33], 19.1%)、BZD/Z-hypnotics (1.23, [1.16-1.31], 18.8%)、antidepressants (1.17, [1.05-1.31], 14.7%)及antiplatelets (1.16, [1.07-1.26], 14.0%)。anticoagulants、antiarrhythmics、antihypertensives、narcotics與急性住院無顯著之相關性；diabetic agents則顯示保護作用 (0.86, [0.77-0.97])。以全部急性住院事件進行分析時，使用narcotics之風險增加未達統計顯著，但僅分析住院天數≥10天之急性住院事件時，風險顯著增加。將各個高風險藥物細分為不同子類別進行分析時急性住院風險不同，急性住院風險最高之antipsychotics及NSAIDs中，又以typical antipsychotics及non-selective NSAIDs之風險較高。依年齡分層分析時，antipsychotics、NSAIDs、diuretics、BZD/Z-hypnotics及antiplatelets在<65歲者和≥65歲者之急性住院風險皆顯著增加，anticonvulsants和antidepressants則只在≥65歲者和急性住院有顯著相關性。研究結論本研究提供一種全新的「主動監測藥物不良事件」之方式，與現有之被動監測機制互補可提供更完整的資訊，本研究中急性住院風險顯著增加之藥物antipsychotics、NSAIDs、anticonvulsants、diuretics、BZD/Z-hypnotics、antidepressants及antiplatelets等，可作為未來臨床研究與政策執行之目標。; Background: Adverse drug events (ADEs) could threaten the health of the patients and imposed a substantial economic burden on the healthcare system. Therefore, efficient identification of severe ADEs, such as ADE-related hospitalizations, can help highlight area in which improvement of treatment practices clinicians and policy-makers can put efforts in. Previous studies have adopted several approaches to identify ADE-related hospitalizations, such as analysis of spontaneous reporting data, medical chart review, and screening diagnostic codes from electronic medical charts databases. However, these methods were limited by under-reporting and reporting bias. Furthermore, most of the studies only examined the number of ADE-related hospitalizations, and did not consider the prevalence of medication exposure within the population. Objectives: To address the limitations of current approaches, we used a case–time–control design to evaluate the association between high-risk medications and emergency hospitalizations from the National Health Insurance Research Database (NHIRD) in Taiwan. Methods: Using data from the Longitudinal Health Insurance Database (LHID) 2000, patients aged 20 years and over and had received at least one outpatient prescription during 2000 to 2011 were included as our study cohort. Among them, emergency hospitalizations and outpatient visits were identified as index visits and reference visits, respectively. The first date of index and reference visit was defined as the index date. Each index visit was then matched to a randomly selected reference visits by age, gender, index date, Charlson Comorbidity Index and number of outpatient visits. For both index and reference visits, the period of 1-14 days and 366-379 days prior to the index date were defined as case period and control period, respectively. The exposure of high-risk medications during the case period and the control period were then compared. High-risk medications included in our study were diabetic agents, diuretics, nonsteroidal anti-inflammatory drugs (NSAIDs), anticoagulants, antiplatelets, antihypertensives, antiarrhythmics, anticonvulsants, antipsychotics, antidepressants, benzodiazepine (BZD)/Z-hypnotics and narcotics. Conditional logistic regression models were used to estimate odds ratios (ORs) with adjustment for time-varying variables, including Charlson Comorbidity Index, number of outpatient visits, number of emergency visits and number of chronic drugs used. Attributable fractions (AFs) were also calculated to determine the proportion of emergency hospitalizations attributable to exposure of high-risk medications. Results: Overall, antipsychotics (adjusted OR: 1.54, 95% confidence interval [1.37-1.73], AF: 35.0%), NSAIDs (1.50, [1.44-1.56], 33.3%), anticonvulsants (1.34, [1.10-1.64], 25.6%), diuretics (1.24, [1.15-1.33], 19.1%), BZD/Z-hypnotics (1.23, [1.16-1.31], 18.8%), antidepressants (1.17, [1.05-1.31], 14.7%) and antiplatelets (1.16, [1.07-1.26], 14.0%) were significantly associated with increased risks of emergency hospitalizations. Such associations were not found in anticoagulants, narcotics, antiarrhythmics and antihypertensives. Diabetic agents showed protective effect (0.86, [0.77-0.97]). However, when we limited our analyses in emergency hospitalizations with a length of stay ≥10 days, the narcotics significantly associated with an increased risk of emergency hospitalizations. In subgroup analysis by pharmacological properties, typical antipsychotics were associated with higher risks of emergency hospitalizations than atypical antipsychotics. Non-selective NSAIDs was linked with higher risk of emergency hospitalizations than COX-2 selective NSAIDs. Age-stratified analyses showed that antipsychotics, NSAIDs, diuretics, BZD/Z-hypnotics, and antiplatelets were significantly associated with emergency hospitalizations in aged<65 years and aged ≥65 years, but anticonvulsants and antidepressants were associated with increased risk of emergency hospitalizations in the elderly (age ≥65 years) only. Conclusion: This study provides an alternative approach for active pharmacovigilance, which may complement the present passive pharmacovigilance system in Taiwan. Future research can focus on medications significantly associated with increased risks of emergency hospitalizations, including antipsychotics, NSAIDs, anticonvulsants, diuretics, BZD/Z-hypnotics, antidepressants and antiplatelets.

高劑量amoxicillin/PPI二合一療法用於一線與救援治療幽門螺旋桿菌感染之評估

2021-06-08T00:01:43Z

標題: 高劑量amoxicillin/PPI二合一療法用於一線與救援治療幽門螺旋桿菌感染之評估; Evaluation of high dose amoxicillin/PPI dual therapy as the first-line and rescue treatments of Helicobacter pylori infection 作者: Chien-Wei Lu; 呂建緯摘要: 研究背景　　幽門螺旋桿菌（Helicobacter pylori）感染為常見的腸胃科感染性疾病，全世界約有一半的人感染幽門螺旋桿菌。幽門螺旋桿菌感染與慢性胃炎、消化性潰瘍、十二指腸潰瘍及胃黏膜淋巴瘤有關，甚至可能發展成胃癌。因此世界衛生組織早於1994年將幽門螺旋桿菌列為第一級的胃癌致癌因子。根據美國、歐洲、亞太地區治療指引，由質子幫浦抑制劑（proton pump inhibitor）、clarithromycin與amoxicillin（或metronidazole）所組成的三合一療法目前仍為根除幽門螺旋桿菌的第一線治療；然而目前許多國家，此療法失敗率已高於兩成，最新2012年歐洲治療指引已建議高抗藥性地區以四合一療法取代現有一線治療。相繼式療法（sequential therapy）是近年來新發展的一種四合一療法，而三合一療法中以levofloxacin取代clarithromycin現階段也被廣泛用於一線治療失敗後之救援治療。此外僅使用質子幫浦抑制劑與amoxicillin的二合一療法，其治癒率隨著不同給藥頻次、劑量與不同品項之質子幫浦抑制劑有很大的變異。研究目的　　本研究主要欲探討高劑量二合一療法分別用於一線或救援治療幽門螺旋桿菌感染的療效與安全性。一線治療將與現行治療指引建議以clarithromycin為基礎的三合一療法和四合一相繼式療法比較，救援治療則與現行建議以levofloxacin為基礎的三合一療法和四合一相繼式療法比較，評估影響各種療程療效的因子，同時針對目前幽門螺旋桿菌對於各種抗生素抗藥性之盛行率與趨勢進行分析與探討。研究材料與方法　　本研究將納入經內視鏡確診患有幽門螺旋桿菌感染引發胃炎、消化性潰瘍與十二指腸潰瘍之成年病人，分為一線治療與救援治療兩部分進行隨機分派試驗。病患若尚未接受過根除治療將納入一線治療組，此部份試驗將評估高劑量二合一療法（rabeprazole 20 毫克與amoxicillin 750 毫克，每日口服四次，共十四天）、相繼式療法（前五天使用rabeprazole 20 毫克與amoxicillin 1000 毫克，每日口服兩次，後五天使用rabeprazole 20 毫克、clarithromycin 500毫克與metronidazole 500毫克，每日口服兩次，共十天）與clarithromycin為基礎的三合一療法（rabeprazole 20 毫克、clarithromycin 500毫克與amoxicillin 1000 毫克，每日口服兩次，共七天）之根除率、副作用及服藥順從性差異；病患若曾接受過根除治療且失敗將納入救援治療組，此部份試驗將評估高劑量二合一療法（同上）、相繼式療法（同上）與levofloxacin為基礎的三合一療法（rabeprazole 20 毫克、levofloxacin 250毫克與amoxicillin 1000 毫克，每日口服兩次，共七天）之根除率、副作用及服藥順從性差異。另外，利用病患經內視鏡切片細菌培養之抗生素敏感性試驗結果，分析尚未接受治療與曾經治療失敗的病患感染各種抗生素抗藥性菌株之盛行率與趨勢。研究結果　　療且失敗的幽門螺旋桿菌感染陽性病人，所有病人以平均比例隨機分配至各組療法。一線治療部分，高劑量二合一療法之根除率為95.0％（95％信賴區間：91.4─98.6）、相繼式療法之根除率為87.1％（95％信賴區間：81.6─92.7）和clarithromycin為基礎的三合一療法之根除率為81.4％（95 %信賴區間：75─87.9）；療效上，高劑量二合一療法顯著地優於相繼式療法與三合一療法（p-value= 0.021與0.0004），而副作用發生率與服藥順從性三組之間皆無顯著性差異。救援治療部分，高劑量二合一療法之根除率為88％（95％信賴區間：79.0─97.0）、相繼式療法之根除率為52％（95％信賴區間：38.2─65.8）和levofloxacin為基礎的三合一療法之根除率為78％（95 %信賴區間：66.5─89.5）。療效上，高劑量二合一療法與levofloxacin為基礎的三合一療法未達統計上顯著差異，但相繼式療法則不適合用於救援治療；副作用發生率與服藥順從性三組之間皆無顯著性差異。研究分析顯示主要影響療效之因子為感染抗藥性菌株。在前後兩部分病人感染amoxicillin、clarithromycin、metronidazole與levofloxacin抗藥性菌株比例，一線治療分別佔1.7％、16.4％、33.8％與16％；而救援治療分別佔5.4％、81.9％、54.4％與22.1％。結論　　高劑量二合一療法可有效用於一線與救援治療幽門螺旋桿菌感染。在一線治療上，高劑量二合一療法不僅療效上顯著地優於clarithromycin為基礎三合一療法，副作用發生率上也與各療法無顯著差異。在救援治療上，高劑量二合一療法也與levofloxacin為基礎的三合一療法一樣有效與安全，且高劑量二合一療法更可有效根除clarithromycin、metronidazole或levofloxacin抗藥性菌株。; Background Helicobacter pylori infection is a common infectious disease and is highly associated with a variety of gastrointestinal disorders. Standard triple therapy consisted of a proton pump inhibitor, clarithromycin and amoxicillin (or metronidazole) has been recommended as first-line treatment for H. pylori infection for many years. However, with the increasing resistance rates to clarithromycin and metronidazole, the eradication rate of standard triple therapy is less than 80% in many countries. Therefore, alternative treatments, such as sequential therapy, are recently recommended as alternative treatment in the areas with high clarithromycin resistance rate according to Maastricht IV guideline. Compared to clarithromycin and metronidazole resistance, primary resistance rate to amoxicillin is usually less than 1%. Yet, the eradication rate of high dose amoxicillin/PPI dual therapy varies among different studies. Objectives The objectives of this study was to compare the efficacy, adverse events and patient adherence of high dose dual therapy (HD), sequential therapy (ST) and clarithromycin-based (CLA-T) triple therapy as the first-line treatment for H. pylori infection and those of HD, ST and levofloxacin-based triple therapy (LEV-T) as the rescue treatment. Also, factors affecting the studied regimens and the prevalence of antimicrobial resistance were investigated. Materials and Methods This prospective randomized study recruited H. pylori-positive patients (≧18 years of age). Treatment naïve patients were randomly assigned to one of the following regimens: (1) HD group-rabeprazole 20 mg + amoxicillin 750 mg four times daily for 14 days, (2) ST group- rabeprazole 20 mg + amoxicillin 1 g twice daily for first 5 days and following by rabeprazole 20 mg, clarithromycin 500 mg and metronidazole 500 mg twice daily for next 5 days, or (3) CLA-T group- rabeprazole 20 mg, clarithromycin 500 mg and amoxicillin 1 g twice daily for 7 days. Patients who had a history of treatment failure were randomly assigned to one of the following regimens: (1) HD group, (2) ST group or (3) LEV-T group- rabeprazole 20 mg, levofloxacin 250 mg and amoxicillin 1 g twice daily for 7 days. Primary end point is the eradication rates of studied regimens, and secondary end point are adverse event rates and patient adherence. Results Between Oct, 2010 and April, 2013, 420 treatment naïve patients and 150 patients who had a history of treatment failure were included. In the first-line treatment, the eradication rates were 95.0% (95% CI=91.4-98.6) in HD group, 87.1% (95% CI=81.6-92.7) in ST group, and 81.4% (95% CI=75-87.9) in CLA-T group. The efficacy of HD group is significantly superior to that of ST group and CLA-T group (p=0.021 and 0.0004). In the rescue treatment, the eradication rates were 88% (95% CI=79-97) in HD group, 52% (95% CI=38.2-65.8) in ST group, and 78% (95% CI=66.5-89.5) in LEV-T group. The efficacy of ST group is significantly worse than that of HD and LEV-T group (p<0.0001). There were no significant difference in the total adverse event rates and in patient adherence between three groups in the first-line and the rescue treatment. Conclusions High dose dual therapy is a well-tolerated and highly effective regimen as the first-line and the rescue treatment for H. pylori infection. In first-line treatment, high dose dual therapy is superior to clarithromycin-based triple therapy. In rescue treatment, high dose dual therapy is also as effective as levofloxacin-based triple therapy, of which both are better than sequential therapy.

類風濕性關節炎患者使用抗腫瘤壞死因子α製劑減量及暫緩使用之研究

2021-07-10T21:43:39Z

標題: 類風濕性關節炎患者使用抗腫瘤壞死因子α製劑減量及暫緩使用之研究; Tapering and Discontinuing TNF-α Inhibitors in Rheumatoid Arthritis Patients 作者: Xuet-Yit Chen; 曾雪玉摘要: 研究背景:類風濕性關節炎（rheumatoid arthritis）的治療過去的二十年有了突破性的發展。在標靶疾病修飾抗風濕病出現後，達標治療(treat-to-target, T2T)的醫療策略變成醫師心中的普遍追求且是容易達到的。但因為標靶疾病修飾抗風濕病藥物藥價昂貴，對國家健康保險支出或個人經濟都是不小的負擔，長期使用也有相關的副作用等疑慮。在患者能長期達到無症狀疾病狀態(remission)後，各治療指引也提出標靶疾病修飾抗風濕病藥物減量的建議。台灣「全民健康保險藥物給付項目及支付標準」也有規定相關的減量及暫緩續用之相關規定。目前低劑量的生物製劑的療效、效果將持續多久尚不明確。因為許多隨機分派試驗納入條件相對嚴格，得出的結論是生物製劑減量是可行的，但暫緩使用會顯著增加疾病復發的風險。因為隨機分配試驗的納入條件和規定與現實世界中病人疾病情形不盡相同，較難反應出到底在常規治療下有多少病人能成功減量或暫緩使用生物製劑。對於最佳的減量時機等研究結果也不一致。台灣也缺乏針對在健保給付限制下生物製劑減量對於病人的疾病的影響。研究目的:本研究分析類風濕性關節炎患者在抗腫瘤壞死因子α抑製劑減量後能夠維持疾病穩定的時間、探討類風濕性關節炎患者能成功減量抗腫瘤壞死因子α抑製劑及維持較久疾病穩定的預測因子 (predictive factors)，並探討因為減量後疾病復發對於病人恢復疾病穩定的影響。研究方法以回溯性世代研究以單一醫學中心病歷資料進行分析，篩選2003/5/2-2017/4/30接受過抗腫瘤壞死因子α抑製劑治療的類風濕性關節炎病人，所有病人以其第一次抗腫瘤壞死因子α抑製劑開方的日期為「進入研究世代日期 (index date)」，並以病人發生死亡、失去後續追蹤或研究結束時間(2020/4/30)為研究終點 (end of study)，且將這些定義為設限 (censor)。在進入研究世代後至病人開始減量為收集病人基本疾病資料的期間則稱為減量前期間 (pre-tapering period)。從病人開始減量至病人有疾病復發為減量期間 (tapering period)。如病人有減量成功並進入停用至復發稱為停用期間 (discontinuation period)。以存活分析抗腫瘤壞死因子α抑製劑減量後疾病可維持穩定的期間中位數。利用比例風險回歸模式分析不同共變項對於類風濕性關節炎維持疾病穩定以及疾病復發的影響。研究結果:共有89位病人有進行減量，，減量後疾病可維持穩定的期間中位數為40.0 (95% CI=28.6-51.3) 個月。有58位病人在未達停藥前有疾病復發，疾病復發率為65.2 %。有9位病人在減量後可暫緩使用抗腫瘤壞死因子α抑製劑，有1位病人直接暫緩使用抗腫瘤壞死因子α抑製劑，另外有22位病人減量後無疾病復發仍持續用低劑量的抗腫瘤壞死因子α抑製劑。進行單變項比例風險迴歸模式分析發現，沒有併用hydroxychloroquine的組別其在抗腫瘤壞死因子α抑製劑減量後的疾病復發的風險較高，且達統計顯著的差異（HR=1.85，95% CI=1.08-3.18，p-value=0.03）。針對病人在抗腫瘤壞死因子α抑製劑減量前疾病狀態，相對可以維持血清性緩解維持≥ 2年，沒有維持血清性緩解(serological remission)達≥ 2年會增加疾病復發的風險，且達統計顯著差異（HR=2.42，95% CI=1.40-4.29，p-value<0.01）。在抗腫瘤壞死因子α抑製劑減量前一年，疾病維持穩定且無復發的病人疾病復發的風險也較減量一年前有疾病復發的病人低（HR=0.40，95% CI= 0.23-0.70，p-value<0.01)。在減量前的平均ESR和CRP越高會顯著增加抗腫瘤壞死因子α抑製劑減量後的疾病復發。減量前的平均ESR每增加1 mm/hr時，風險比增加了0.04倍，且達顯著差異（p-value<0.01）。減量前的平均CRP每增加0.1 mg/dL時，風險比增加了1.28倍，且達顯著差異（p-value=0.02）。若進行多變項分析，只有減量前的平均ESR會顯著增加抗腫瘤壞死因子α抑製劑減量後疾病復發的風險。平均ESR每增加1 mm/hr時，風險比增加了0.03倍，且達顯著差異（p-value<0.01）。研究結論:本論文從真實世界資料分析，發現類風濕性關節炎患者常規使用抗腫瘤壞死因子α抑製劑時，疾病控制狀況和後續是否能成功減量或暫緩使用有相關。給予低劑量抗腫瘤壞死因子α抑製劑維持疾病穩定，將能減少不必要的醫療浪費且能降低副作用。; Background:With the emergence of biologic disease-modifying antirheumatic drugs (bDMARDs), the treatment options of rheumatoid arthritis (RA) have improved tremendously since these 20 years. Treat-to-target strategy, treating the patient aggressively to achieve measured goals, such as remission or low disease activity is now realistic. However, the costs of bDMARDs are high and healthcare resources are under growing economic pressure. Drug reimbursement and pricing policy in Taiwan regulates the use of bDMARDs in RA. Besides, RA patients with symptom-free disease states continuous use of life-long, full dose bDMARD may provide more harms than benefits. Therefore, many treatment guidelines have proposed dose reduction if RA patients reached sustained remission. There are a lot of studies that are dedicated to find out relapse rate if bDMARDs are being tapered or discontinued, also predictive factors of successfully tapered bDMARDs. However, there are no consistent findings. Objective This study aims to analyses time to disease relapse of RA patients if TNF-α inhibitors are being tapered, the predictive factors that are associated with successful taper of TNF-α inhibitors. Also, investigate the effects associated with dose tapering of TNF-α inhibitors. Methods This is a retrospective cohort study with patients who were diagnosed with RA and were treated with TNF-α inhibitors between May 2, 2003 and April 30, 2017 at medical center. All patients are followed the first dose of TNF-α inhibitors (index date) loss follow up or study end (2020/4/30). Baseline characteristics are collected during pre-tapering period. I calculate the disease relapse rate and time to disease relapse using survival analysis (Kaplan-Meier survival curve). Cox-proportional hazards regression model is applied to examine any predictive factors associated with successful taper of TNF-α inhibitors. Repeated measured ANOVA and paired t test are used to measure the effect associated with the tapering of TNF-α inhibitors. Results There are 90 patients included in this cohort study, 89 patients underwent tapering of TNF-α inhibitors. The median of tapering maintenance period is 40.0 (95% CI 28.6-51.3) months. Fifty-eight patients had disease relapse before they can discontinue TNF-α inhibitors. Disease relapse rate of tapering of TNF-α inhibitors is 65.2%. There are 9 patients succeeding in tapering and discontinuing TNF-α inhibitors, and 1 patient directly discontinued TNF-α inhibitors. There are 22 patients maintaining low dose TNF-α inhibitors. Using univariate cox proportional regression model, no concomitant hydroxychloroquine (HR=1.85, 95% CI=1.08-3.18, p-value=0.03), and no sustained serological remission for ≥ 2 years (HR=2.42, 95% CI 1.40-4.29, p-value<0.01) are associated with increased risk of disease relapse, while no pre-taper flare within 1 year before TNF-α inhibitors being tapered (HR=0.40, 95% CI 0.23-0.70, p-value<0.01) is associated with decreased risk of disease relapse. Higher ESR and CRP before TNF-α inhibitors being tapered are associated with increased risk of disease relapse. However, the multivariate cox proportional regression model was performed, only increase of ESR before TNF-α inhibitors being tapered was associated with increase risk of disease relapse. The hazard rate increases by 0.03 with the increase of ESR by 1 mm/hr. Fifty-eight patients with disease relapse had significant increase of ESR even after TNF-α inhibitors dose was escalated for rescue. Conclusion This is the first time to show mandatoy dose reduction from real-world evidence that the disease control status under standard use of TNF-α inhibitors is associated with successfully tapering or discontinuing TNF-α inhibitors in the RA patients. Low dose TNF-α inhibitors which can sustain disease stable would have the benefit of decreasing unwanted adverse effects and reducing unnecessary health resources.

顆粒性白血球生長激素於化學治療引發嗜中性白血球低下之成本效果分析

2021-06-16T13:32:55Z

標題: 顆粒性白血球生長激素於化學治療引發嗜中性白血球低下之成本效果分析; Cost-Effectiveness Analysis of G-CSF Prophylaxis in Chemotherapy Induced Neutropenic Events 作者: Tsun-Jen Wen; 溫存真摘要: 研究背景：顆粒性白血球生長激素 (granulocyte colony-stimulating factor, G-CSF)在預防對癌症患者的嗜中性白血球減少症併發燒 (febrile neutropenia, FN)上之功效已被證實。因此目前臨床治療指引皆建議於FN的高危險群，可預防性使用G-CSF。然而關於預防性使用G-CSF其經濟效益上的影響的研究結果卻多有衝突。而與臨床指引相左，台灣於G-CSF的健保給付規定僅針對血液腫瘤病人給予初級預防性G-CSF之給付。研究目的：本研究之目的為藉由使用醫院資料庫與全民健保資料庫，分析於健保體制下，於非何杰金氏淋巴癌 (non-Hodgkin’s lymphoma, NHL) 與乳癌病人預防性使用G-CSF之成本效益 (cost-effectiveness)。研究方法：本研究納入於2001至2010於健保資料庫中新診斷為乳癌或NHL，並於觀察期間開始使用新的化學治療處方者。於醫院資料庫則納入診斷為乳癌或NHL之病人，乳癌病人於2010年，NHL病人則於2010至2011年開始新化學治療處方者。所有病人皆以開始化學治療之第一天當成「進入研究世代日期 (index date)」，而後追蹤至化學治療完成，或「進入研究世代日期」後一年為止。根據使用G-CSF的方式，病人進一步被分為「初級預防」、「次級預防」、「無預防」三組。使用G-CSF的方式、病人有無發生FN和其相關費用皆以化療週期為單位進行資料收集。以廣益估計方程式 (generalized estimating equations, GEE)分析 G-CSF使用方式對FN發生之影響；成本效益分析方面，計算「初級預防」與「次級預防」之增量成本效益，並進行敏感度分析。研究結果：由健保資料庫之乳癌病患中可看出預防性使用G-CSF於下降嗜中性白血球低下之風險有顯著效果 (初級預防：OR=0.18，95%CI=0.13-0.25；次級預防：OR=0.54，95%CI=0.36-0.81)。於降低FN的風險上則未觀察出這樣的效果。對於NHL的病人而言，在健保資料庫中G-CSF的初級預防顯著的下降發生嗜中性白血球低下與FN的風險 (OR=0.17，95%CI=0.11-0.27)，然而使用G-CSF進行次級預防則沒有相同的效果 (OR=0.79，95%CI=0.56-1.12)。針對醫院病人進行分析時，預防性使用G-CSF亦未顯示出減少嗜中性白血球與FN風險的效果。使用健保資料庫的數據進行分析時，相較於無預防，初級預防為下降一次FN的發生所需增加的花費在乳癌病人與NHL病人分別為NT$30,732與NT$1,704。相反的，當使用醫院資料庫進行分析時，相較於無預防，初級預防為下降一次FN所需增加的花費於乳癌病人為NT$87,115；而於NHL病人間，初級預防並不合乎成本效益。次級預防在兩種癌症與兩個資料庫裡皆不合乎成本效益。研究結論：研究中顯示無論是初級抑或次級預防，兩者皆有利於降低嗜中性白球下降之風險；相較於次級預防，初級預防更具成本效益。此外，在台灣健保制度下，初級預防性使用G-CSF在NHL病人上，相較於乳癌病人更具成本效益。; Background: The beneficial effect of granulocyte colony-stimulating factor (G-CSF) prophylaxis on reducing neutropenia and febrile neutropenia (FN) in cancer patients is well-established. Therefore, prophylactic G-CSF is recommended by recent clinical guidelines to manage patients with high risk of FN. However, the economic impact of G-CSF prophylaxis is conflicting between studies. Most studies were based on claim database. The validity of database in detecting neutropenic events still remained uncertain. Furthermore, against to recommendation of guidelines, regulations in Taiwan’s national health insurance (NHI) limited the reimbursement of primary prophylactic G-CSF among patients with hematologic malignancy. Objectives: The objectives of this study were to assess the cost-effectiveness of G-CSF prophylaxis among breast cancer and non-Hodgkin’s lymphoma (NHL) patients under Taiwan’s NHI system by using electronic medical record from one cancer center and national health insurance research database (NHIRD). Methods: Eligible patients were those who newly diagnosed with breast cancer or NHL only, and initiated a new chemotherapy regimen between 2001 and 2010 in NHIRD. For patients in the hospital, those who diagnosed with breast cancer only and initiated a chemotherapy regimen in 2010 were included. Patients diagnosed with NHL only and initiated a new chemotherapy regimen between 2010 and 2011 were also included. All patients were followed until the planned chemotherapy courses were completed or one year after the first date of chemotherapy regimen. Patients were further categorized into three subgroups as “primary prophylaxis”, “secondary prophylaxis” and “no prophylaxis”. The purpose of G-CSF use, occurrence of neutropenia and FN and related costs were evaluated by cycles. Generalized estimating equations (GEEs) were used to examine the impact of G-CSF use on risk of neutropenia and FN. The incremental cost-effectiveness of primary and secondary prophylactic G-CSF were calculated and sensitivity analyses were performed. Results: Significant beneficial effects of prophylactic G-CSF were shown in reducing neutropenia risk among breast cancer patients retrieved from NHIRD (primary prophylaxis: OR=0.18, 95%CI=0.13-0.25; secondary prophylaxis: OR=0.54, 95%CI=0.36-0.81). No such effect were shown in reducing FN risk. For NHL patients, primary prophylactic G-CSF reduced risk of neutropenia and FN significantly in NHIRD (OR=0.17, 95%CI=0.11-0.27) while secondary prophylactic G-CSF did not show the same result (OR=0.79, 95%CI=0.56-1.12). Beneficial effects were not shown when analysis performed in hospital patients. When using data from NHIRD, the incremental cost per FN reduced of primary prophylaxis is NT$30,732 and NT$1,704 among patients with breast cancer and NHL, respectively, compared to no prophylaxis. In contrast, the incremental cost-effectiveness ratio of primary prophylaxis in the hospital is NT$87,115 among patients with breast cancer, and is more costly in NHL patients when compared with no prophylaxis. Secondary prophylaxis is more costly compared with no prophylaxis and primary prophylaxis in both cancer and data sources. Conclusion: We found that both primary prophylactic G-CSF and secondary prophylactic G-CSF have beneficial effect on reducing neutropenia risk, while primary but not secondary prophylactic G-CSF was more cost-effective. In addition, primary prophylactic G-CSF is more cost-effective for NHL patients than for breast cancer patients under Taiwan’s NHI system.