新型抗癲癇藥單藥治療新診斷癲癇患者保留率的對比研究
發(fā)布時(shí)間：2018-08-13 12:39
【摘要】：背景:癲癇是神經(jīng)系統(tǒng)的常見病和多發(fā)病,長期藥物治療是目前公認(rèn)的主要措施,新型抗癲癇藥因其廣泛的抗癇譜、良好的發(fā)作控制率及較少的不良反應(yīng)發(fā)生率優(yōu)勢在臨床得到廣泛應(yīng)用,已有多項(xiàng)研究證實(shí)了其有效性及耐受性。保留率是近年來臨床上評(píng)價(jià)癲癇患者長期治療效果的新指標(biāo),綜合反應(yīng)了藥物療效、耐受性及適用性,同時(shí)包含了患者的個(gè)人意愿等,對抗癲癇治療藥物的選擇具有實(shí)際的臨床指導(dǎo)意義,已得到ILAE專家們的認(rèn)可。目的:比較4種常用新型抗癲癇藥(Antiepileptic drugs,AEDs)單藥治療新診斷癲癇患者的2年保留率,綜合評(píng)估藥物長期治療性能,為癲癇患者的臨床選藥提供參考依據(jù)。方法:采用回顧性分析的方法,收集2007年1月-2016年10月在大連醫(yī)科大學(xué)附屬第一醫(yī)院癲癇門診就診的癲癇患者臨床資料,從中篩選出分別接受了托吡酯(topiramate,TPM)、拉莫三嗪(lamotrigine,LTG)、奧卡西平(oxcarbazepine,OXC)、左乙拉西坦(levetiracetam,LEV)正規(guī)單藥治療的新診斷癲癇患者共計(jì)376例,隨訪觀察2年,記錄治療過程中的發(fā)作頻率變化、不良反應(yīng)、停藥原因。分別在6個(gè)月、12個(gè)月和2年時(shí)計(jì)算4種新型AEDs單藥治療的保留率,保留率=隨訪時(shí)堅(jiān)持初始單藥治療人數(shù)/起始該藥治療的總?cè)藬?shù)×100%;通過Kaplan-Meier生存分析法計(jì)算累計(jì)保留率。對保留達(dá)2年的患者,分別以有效率、年無發(fā)作率為指標(biāo)評(píng)價(jià)臨床療效;分析比較各自停藥原因。使用SPSS 17.0軟件進(jìn)行統(tǒng)計(jì)學(xué)處理。結(jié)果:1、符合納入和排除標(biāo)準(zhǔn)的患者376例,TPM組134例,LTG組80例,OXC 組 79 例,LEV 組 83 例。女性 174 例(46.3%),男性 202 例(53.7%)。年齡1.5-86歲,平均年齡31.8±19.2歲。用藥前病程4天-55年。原發(fā)性癲癇167例(44.4%),繼發(fā)性癲癇209例(55.6%)。部分性發(fā)作248例(66.0%),全面性發(fā)作128例(34.0%)。Cox回歸模型示性別、年齡、用藥前病程、病因、發(fā)作類型不是影響保留率的潛在危險(xiǎn)因素(P0.05)。2、保留率:6個(gè)月時(shí),保留率為LTG組91.3%、TPM組82.1%、LEV組79.5%、OXC組78.5%,4組間比較差異無統(tǒng)計(jì)學(xué)意義(P0.05)。12個(gè)月時(shí),保留率為LTG 組 81.3%、TPM 組 74.6%、LEV 組 66.3%、OXC 組 65.8%,4 組間比較差異無統(tǒng)計(jì)學(xué)意義(P0.05)。2年時(shí),保留率依次為LTG組70.0%、LEV組63.9%、OXC組59.5%、TPM組58.2%,4組間比較無顯著差異(P0.05)。觀察結(jié)束時(shí)(2年),采用Kaplan-Meier生存分析法計(jì)算的累積保留率顯示上述類似結(jié)果。3、臨床療效:2年時(shí)有效率依次為LTG組91.1%、LEV組90.6%、TPM組87.2%、OXC組85.1%,4組間比較無顯著差異(P0.05)。2年時(shí)年無發(fā)作率依次為TPM組 61.5%、LEV 組 60.4%、LTG 組 57.1%、OXC 組38.3%,差異無統(tǒng)計(jì)學(xué)意義(p0.05)。4、導(dǎo)致停藥的不良反應(yīng):TPM組最常見的為中樞神經(jīng)系統(tǒng)問題,表現(xiàn)為記憶減退、反應(yīng)遲鈍,其次為泌尿系結(jié)石,其他少見為體重下降、皮疹。LTG組主要為肝功異常、皮疹。OXC組主要為皮疹,其次為中樞神經(jīng)系統(tǒng)問題(困倦)。LEV組主要為精神行為異常,表現(xiàn)為易激惹、行為紊亂,其次為中樞神經(jīng)系統(tǒng)問題,表現(xiàn)為困倦。5、停藥原因:導(dǎo)致4組新型AEDs停藥的首要原因均為無效,分別占停藥原因的LTG組75.0%、LEV組70.0%、OXC組46.9%、TPM組44.6%,其中,LTG組與OXC組、TPM組比較差異有統(tǒng)計(jì)學(xué)意義(P0.05),LEV組與TPM組比較差異有統(tǒng)計(jì)學(xué)意義(P0.05),其他藥物之間比較,差異無統(tǒng)計(jì)學(xué)意義(P0.05)。其次,停藥原因?yàn)椴涣挤磻?yīng),分別占停藥原因的TPM組32.1%、OXC組31.2%、LTG組20.8%、LEV組13.3%,4組間比較差異無統(tǒng)計(jì)學(xué)意義(P0.05)。其他停藥原因包括依從性差、經(jīng)濟(jì)原因、聯(lián)合應(yīng)用其他抗癲癇藥。6、2年時(shí)每種AEDs平均日劑量停藥組高于保留組,差異均有統(tǒng)計(jì)學(xué)意義(P0.05)。結(jié)論:1、4種新型AEDs單藥治療的保留率在2年內(nèi)均逐漸下降;LTG組在各階段保留率最高,OXC組在6個(gè)月、12個(gè)月時(shí)保留率最低,TPM組在2年時(shí)保留率最低。2、4種新型AEDs單藥治療的臨床療效相當(dāng)。3、導(dǎo)致4種新型AEDs停藥的首要原因均為無效,其次為不良反應(yīng)。
[Abstract]:BACKGROUND: Epilepsy is a common and frequently-occurring disease of the nervous system. Long-term drug therapy is currently recognized as the main measure. New antiepileptic drugs have been widely used in clinic because of their broad antiepileptic spectrum, good seizure control rate and less adverse reaction rate. Many studies have confirmed their effectiveness and tolerance. It is a new index for evaluating the long-term therapeutic effect of epilepsy patients in recent years. It comprehensively reflects the efficacy, tolerance and applicability of drugs, and also includes the individual wishes of patients. It has practical clinical significance for the selection of antiepileptic drugs and has been approved by ILAE experts. Objective: To compare four new antiepileptic drugs. The two-year retention rate of antiepileptic drugs (AEDs) in newly diagnosed epilepsy patients was evaluated comprehensively to provide reference for the clinical selection of epileptic patients. Clinical data of 376 newly diagnosed epilepsy patients who received topiramate (TPM), lamotrigine (LTG), oxcarbazepine (OXC) and levetiracetam (LEV) were selected. The frequency of seizures and adverse reactions during the treatment were recorded. Reasons for discontinuation were calculated at 6 months, 12 months, and 2 years, respectively. The retention rate = the number of patients who had adhered to the initial single-drug treatment at follow-up * 100%; the cumulative retention rate was calculated by Kaplan-Meier survival analysis. Results: 1. 376 patients, 134 patients in TPM group, 80 patients in LTG group, 79 patients in OXC group, 83 patients in LEV group, 174 women (46.3%) and 202 men (53.7%) met the inclusion and exclusion criteria. Cox regression model showed that sex, age, course of treatment, etiology, seizure type were not the potential risk factors affecting the retention rate (P 0.05). The retention rate was 91.3% in LTG group at 6 months. At 12 months, the retention rate was 81.3% in LTG group, 74.6% in TPM group, 66.3% in LEV group, 65.8% in OXC group. There was no significant difference among the four groups (P 0.05). At 2 years, the retention rate was 70.0% in LTG group, 63.9% in LEV group, 59.5% in OXC group, 58.2% in TPM group and 58.2% in OXC group. At the end of the observation (2 years), the cumulative retention rate calculated by Kaplan-Meier survival analysis showed the similar results. 3. Clinical efficacy: at 2 years, the effective rate was 91.1% in LTG group, 90.6% in LEV group, 87.2% in TPM group, 85.1% in OXC group, and there was no significant difference among the four groups (P 0.05). At 2 years, the annual no attack rate was 61.5% in TPM group and 61.5% in LEV group. 60.4%, LTG group 57.1%, OXC group 38.3%, the difference was not statistically significant (p0.05). 4, resulting in withdrawal of adverse reactions: TPM group the most common central nervous system problems, for memory loss, slow response, followed by urinary calculi, other rare for weight loss, rash. LTG group mainly for liver dysfunction, rash. OXC group mainly for rash, its most common rash. Secondly, the central nervous system problems (drowsiness). LEV group mainly for mental behavior disorders, irritability, behavior disorders, followed by the central nervous system problems, performance drowsiness. 5. Drug withdrawal reasons: leading to the four groups of new AEDs withdrawal of the primary causes were ineffective, accounting for 75.0% of the LTG group, 70.0% of LEV group, 46.9% of OXC group, 44.6% of TPM group, respectively. There was significant difference between LTG group and OXC group, TPM group (P 0.05), LEV group and TPM group (P 0.05), and there was no significant difference between other drugs (P 0.05). Secondly, the reasons for drug withdrawal were adverse reactions, which accounted for 32.1% of TPM group, 31.2% of OXC group, 20.8% of LTG group, 13.3% of LEV group. There was no significant difference between the two groups (P 0.05). Other reasons for withdrawal included poor compliance, economic reasons, combined use of other antiepileptic drugs. Retention rate was the highest in OXC group at 6 months and the lowest at 12 months. Retention rate was the lowest in TPM group at 2 years. The clinical efficacy of four new AEDs monotherapy was similar. 3. The primary cause of discontinuation of four new AEDs was ineffective, followed by adverse reactions.
【學(xué)位授予單位】：大連醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R742.1
，
本文編號(hào)：2181019
[Abstract]:BACKGROUND: Epilepsy is a common and frequently-occurring disease of the nervous system. Long-term drug therapy is currently recognized as the main measure. New antiepileptic drugs have been widely used in clinic because of their broad antiepileptic spectrum, good seizure control rate and less adverse reaction rate. Many studies have confirmed their effectiveness and tolerance. It is a new index for evaluating the long-term therapeutic effect of epilepsy patients in recent years. It comprehensively reflects the efficacy, tolerance and applicability of drugs, and also includes the individual wishes of patients. It has practical clinical significance for the selection of antiepileptic drugs and has been approved by ILAE experts. Objective: To compare four new antiepileptic drugs. The two-year retention rate of antiepileptic drugs (AEDs) in newly diagnosed epilepsy patients was evaluated comprehensively to provide reference for the clinical selection of epileptic patients. Clinical data of 376 newly diagnosed epilepsy patients who received topiramate (TPM), lamotrigine (LTG), oxcarbazepine (OXC) and levetiracetam (LEV) were selected. The frequency of seizures and adverse reactions during the treatment were recorded. Reasons for discontinuation were calculated at 6 months, 12 months, and 2 years, respectively. The retention rate = the number of patients who had adhered to the initial single-drug treatment at follow-up * 100%; the cumulative retention rate was calculated by Kaplan-Meier survival analysis. Results: 1. 376 patients, 134 patients in TPM group, 80 patients in LTG group, 79 patients in OXC group, 83 patients in LEV group, 174 women (46.3%) and 202 men (53.7%) met the inclusion and exclusion criteria. Cox regression model showed that sex, age, course of treatment, etiology, seizure type were not the potential risk factors affecting the retention rate (P 0.05). The retention rate was 91.3% in LTG group at 6 months. At 12 months, the retention rate was 81.3% in LTG group, 74.6% in TPM group, 66.3% in LEV group, 65.8% in OXC group. There was no significant difference among the four groups (P 0.05). At 2 years, the retention rate was 70.0% in LTG group, 63.9% in LEV group, 59.5% in OXC group, 58.2% in TPM group and 58.2% in OXC group. At the end of the observation (2 years), the cumulative retention rate calculated by Kaplan-Meier survival analysis showed the similar results. 3. Clinical efficacy: at 2 years, the effective rate was 91.1% in LTG group, 90.6% in LEV group, 87.2% in TPM group, 85.1% in OXC group, and there was no significant difference among the four groups (P 0.05). At 2 years, the annual no attack rate was 61.5% in TPM group and 61.5% in LEV group. 60.4%, LTG group 57.1%, OXC group 38.3%, the difference was not statistically significant (p0.05). 4, resulting in withdrawal of adverse reactions: TPM group the most common central nervous system problems, for memory loss, slow response, followed by urinary calculi, other rare for weight loss, rash. LTG group mainly for liver dysfunction, rash. OXC group mainly for rash, its most common rash. Secondly, the central nervous system problems (drowsiness). LEV group mainly for mental behavior disorders, irritability, behavior disorders, followed by the central nervous system problems, performance drowsiness. 5. Drug withdrawal reasons: leading to the four groups of new AEDs withdrawal of the primary causes were ineffective, accounting for 75.0% of the LTG group, 70.0% of LEV group, 46.9% of OXC group, 44.6% of TPM group, respectively. There was significant difference between LTG group and OXC group, TPM group (P 0.05), LEV group and TPM group (P 0.05), and there was no significant difference between other drugs (P 0.05). Secondly, the reasons for drug withdrawal were adverse reactions, which accounted for 32.1% of TPM group, 31.2% of OXC group, 20.8% of LTG group, 13.3% of LEV group. There was no significant difference between the two groups (P 0.05). Other reasons for withdrawal included poor compliance, economic reasons, combined use of other antiepileptic drugs. Retention rate was the highest in OXC group at 6 months and the lowest at 12 months. Retention rate was the lowest in TPM group at 2 years. The clinical efficacy of four new AEDs monotherapy was similar. 3. The primary cause of discontinuation of four new AEDs was ineffective, followed by adverse reactions.
【學(xué)位授予單位】：大連醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R742.1
，
本文編號(hào)：2181019
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