Apremilast不同用药方案治疗银屑病关节炎的疗效和安全性的系统评价
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篇名: Apremilast不同用药方案治疗银屑病关节炎的疗效和安全性的系统评价
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摘要: 目的:系统评价Apremilast不同用药方案治疗银屑病关节炎的疗效和安全性,以探讨临床最佳用药方案(剂量、给药频率、疗程)。方法:计算机检索万方数据、维普网、中国期刊全文数据库、中国生物医学文献数据库、PubMed、Embase、Ebsco和Cochrane图书馆、“www.clinictrials.gov”等,检索时限均为建库起至2018年3月27日,收集不同用药方案的Apremilast(试验组)对比安慰剂(对照组)治疗银屑病关节炎疗效[达到美国风湿病学会(ACR)评分标准改善程度≥20%(ACR20)的患者比例(ACR20应答率)、健康评估问卷残疾指数(HAQ-DI)评分]和安全性(不良反应发生率)的随机对照试验(RCT),对符合纳入标准的临床研究进行质量评价和资料提取后,采用RevMan 5.3统计软件进行Meta分析。结果:共纳入6项研究,合计2 443例患者。Meta分析结果显示,从日剂量看,无论疗程为16周或24周,日剂量40 、60 mg患者的ACR20应答率、HAQ-DI评分比较,差异均无统计学意义(P>0.05);日剂量40 mg的患者腹泻[OR=0.69,95%CI(0.50,0.95),P=0.02]、头痛 [OR=0.65,95%CI(0.44,0.95),P=0.03]、恶心[OR=0.56,95%CI(0.40,0.77),P=0.000 5]的发生率显著低于日剂量60 mg的患者。从用药频率看,相同日剂量(40 mg)下,qd或bid患者的ACR20应答率、HAQ-DI评分、不良反应发生率比较,差异均无统计学意义(P>0.05)。从疗程看,当日剂量为40 mg时,给药16周和24周患者的ACR20应答率、HAQ-DI评分比较,差异均无统计学意义(P>0.05);当日剂量为60 mg 时,给药16周患者的ACR20应答率显著高于给药24周[OR=1.35,95%CI(1.08,1.71),P=0.01],但HAQ-DI评分比较,差异无统计学意义(P=0.78)。但敏感性分析发现,剔除某异质性较大的研究后,疗程为16周时,日剂量40 mg患者的ACR20应答率显著低于日剂量60 mg的患者[OR=0.71,95%CI(0.55,0.92),P=0.02];其余结果无明显改变。结论:Apremilast治疗银屑病关节炎,日剂量60 mg疗效较日剂量40 mg有优势,但随着用药时间延长,该优势逐渐减弱;16周的疗程可能已经足够,用药时间延长并未显著增加疗效;但具体用药方案仍应综合考虑患者的个体差异、依从性及经济负担。上述结果尚需更多高质量的临床研究加以验证。
ABSTRACT: OBJECTIVE: To systematically evaluate therapeutic efficacy and safety of different dosage regimens of apremilast in the treatment of psoriatic arthritis, and to investigate the optimal dosage regimens (dose, frequency of dosing, treatment course). METHODS: Retrieved from Wanfang database, VIP, CJFD, CBM, PubMed, Embase, Ebsco and Cochrane library, “www.clinictrials.gov”, randomized controlled trial (RCTs) about therapeutic efficacy [the proportion of patients with ACR scoring criteria improvement degree≥20% (ACR20 response rate); HAQ-DI score] and safety [the incidence of adverse drug event] of different regimens of apremilast (trial group) versus placebo (control group) in treatment of psoriatic arthritis were collected from database establishment to March 27, 2018. After quality evaluation and data extraction for clinical studies meeting inclusion criteria, Meta-analysis was performed by using RevMan 5.3 statistical software. RESULTS: Totally 6 studies were included, involving 2 443 patients. The results of Meta- analysis showed that for daily dose, there was no statistical significance in ACR20 response rate or HAQ-DI score among patients with daily dose of 40, 60 mg whether treatment course was 16 weeks or 24 weeks (all P>0.05). The incidence of diarrhea [OR=0.69, 95%CI(0.50,0.95), P=0.02], headache [OR=0.65, 95%CI(0.44,0.95), P=0.03] and nausea in patients with daily dose 40 mg were significantly lower than patients with daily dose 60 mg. For dosing frequency, there was no statistical significance in ACR20 response rate, HAQ-DI score or the incidence of ADR among patients receiving same daily dose (40 mg) once a day or twice a day. For treatment course, when the daily dose was 40 mg, there was no statistical significance in ACR20 response rate and HAQ-DI score between 16 weeks and 24 weeks (all P>0.05). When the daily dose was 60 mg, ACR20 response rate of patients receiving 16 weeks of treatment was significantly higher than that of patients receiving 24 weeks of treatment [OR=1.35, 95% CI(1.08,1.71), P=0.01]; there was no statistical significance in HAQ-DI score (P=0.78). Sensitivity analysis showed that after excluding the studies with great heterogeneity, when treatment course was 16 weeks, the response rate of ACR20 in patients receiving daily dose of 40 mg was significantly lower than those receiving daily dose of 60 mg [OR=0.71, 95%CI(0.55,0.92), P=0.02]. There was no significant change from the original results. CONCLUSIONS: For apremilast in the treatment of psoriatic arthritis, therapeutic efficacy of patients receiving daily dose of 60 mg was better than those of patients receiving daily dose of 40 mg; as the extension of medication time, the advantage gradually weakened. 16 weeks of treatment course may be enough. Prolonged medication duration did not significantly increase therapeutic efficacy. For specific dosage regimens, individual differences, compliance and financial burden should be taken into account. The above results need to be verified by more high-quality clinical studies.
期刊: 2018年第29卷第21期
作者: 龚小芳,杨婷,何成松,冯碧敏,叶云,邹榆红,王国俊
AUTHORS: GONG Xiaofang,YANG Ting,HE Chengsong,FENG Bimin,YE Yun,ZOU Yuhong,WANG Guojun
关键字: 银屑病关节炎;Apremilast;随机对照试验;Meta分析;疗效;用药方案
KEYWORDS: Psoriatic arthritis; Apremilast; Randomized controlled trial; Meta-analysis; Therapetic efficacy; Dosage regimens
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