目的:银屑病关节炎(PsA),是一种复杂的炎症性关节病,具有异质性的疾病表现。尽管有庞大的治疗设备,相当比例的患者的疾病控制是次优的。这项研究的目的是评估Janus激酶抑制剂(JAKI)的安全性和有效性。在治疗PsA的关键临床领域,包括外周关节炎,牛皮癣,附着点炎和指炎.
方法:通过使用EMBASE进行系统的文献检索,确定了JAKi在PsA中的随机安慰剂对照试验(RCT)。PubMed和CENTRAL。所有纳入的研究都进行了荟萃分析。
结果:共纳入5个随机对照试验。患者被随机分配到托法替尼(n=474),filgotinib(n=65),upadacitinib(n=1281)或安慰剂(n=937)。与安慰剂相比,JAKi治疗在所有主要结局指标中均具有优异的疗效:美国风湿病学会(ACR)20(风险比[RR]2.10,[95%CI1.86-2.37],P<.00001,I2=19%);ACR50(RR3.43,[95%CI2.37-4.96],P<.00001,I2=66%);ACR70(RR4.57,[95%CI1.83-11.44],P=.001,I2=82%);银屑病面积和严重程度指数75(RR2.96,[95%CI2.44-3.58],P<.00001,I2=0%);附着点炎消退(RR1.82,[95%CI1.56-2.12],P<.00001,I2=0%);指炎消退(RR1.85,[95%CI1.57-2.16],P<.00001,I2=0%)。JAKI与不良事件总体风险增加相关(RR1.14,[95%CI1.07-1.21],P=0.0001,I2=0%),感染风险增加(RR1.23,[95%CI1.08-1.39],P=.001,I2=0%)与安慰剂。
结论:该汇总分析证明了JAKi在治疗PsA的关键临床领域中的功效。然而,它们与不良事件的风险增加有关,包括感染。需要进一步的研究来证实这些发现并进一步阐明安全性。
OBJECTIVE: Psoriatic arthritis (PsA), is a complex inflammatory arthropathy with a heterogenous spectrum of disease presentation. Despite the vast therapeutic armamentarium, disease control in a considerable proportion of patients is suboptimal. The aim of this study was to assess the safety and efficacy of Janus kinase inhibitors (JAKi), in the management of key clinical domains of PsA including peripheral arthritis, psoriasis, enthesitis and dactylitis.
METHODS: Randomized placebo-controlled trials (RCTs) of JAKi in PsA were identified by a systematic literature search using EMBASE, PubMed and CENTRAL. All included studies underwent meta-analysis.
RESULTS: A total of 5 RCTs were included. Patients were randomized to tofacitinib (n = 474),
filgotinib (n = 65), upadacitinib (n = 1281) or placebo (n = 937). JAKi treatment was associated with superior efficacy across all primary outcome measures vs placebo: American College of Rheumatology (ACR) 20 (risk ratio [RR] 2.10, [95% CI 1.86-2.37], P < .00001, I2 = 19%); ACR 50 (RR 3.43, [95% CI 2.37-4.96], P < .00001, I2 = 66%); ACR 70 (RR 4.57, [95% CI 1.83-11.44], P = .001, I2 = 82%); Psoriasis Area and Severity Index 75 (RR 2.96, [95% CI 2.44-3.58], P < .00001, I2 = 0%); enthesitis resolution (RR 1.82, [95% CI 1.56-2.12], P < .00001, I2 = 0%); and dactylitis resolution (RR 1.85, [95% CI 1.57-2.16], P < .00001, I2 = 0%). JAKi were associated with an overall increased risk of adverse events (RR 1.14, [95% CI 1.07-1.21], P = .0001, I2 = 0%) with increased risk of infection (RR1.23, [95% CI 1.08-1.39], P = .001, I2 = 0%) vs placebo.
CONCLUSIONS: This pooled analysis demonstrates the efficacy of JAKi in treating key clinical domains of PsA. However, they are associated with an increased risk of adverse events, including infection. Further studies are required to corroborate these findings and further elucidate the safety profile.