Comparative Efficacy and Safety of Peficitinib 25, 50, 100, and 150 mg in Patients with Active Rheumatoid Arthritis: A Bayesian Network Meta-Analysis of Randomized Controlled Trials.
比较培菲替尼 25 、 50 、 100 和 150 mg治疗活动性类风湿关节炎患者的疗效和安全性: 随机对照试验的贝叶斯网络荟萃分析。
- 作者列表："Lee YH","Song GG
BACKGROUND AND OBJECTIVE:Peficitinib, a JAK3-selective inhibitor that blocks the signal transduction and then suppresses immune responses, has been developed for the treatment of patients with moderate to severe active rheumatoid arthritis (RA). We assessed the relative efficacy and safety of once-daily administration of peficitinib (a JAK3-selective inhibitor) 25 mg, 50 mg, 100 mg, and 150 mg in patients with active RA. METHODS:A Bayesian network meta-analysis was conducted to combine direct and indirect evidence from eligible randomized controlled trials (RCTs). The literature search was performed up to May 2019 using MEDLINE, Embase, and the Cochrane Controlled Trials Register. RESULTS:Three RCTs involving 948 patients met the inclusion criteria. There were ten pairwise comparisons, including five direct comparisons and five interventions. The American College of Rheumatology 20% (ACR20) response rate was significantly higher in the peficitinib 150-mg group than in the placebo group (odds ratio (OR): 3.61; 95% credible interval (CrI): 2.35-5.57). Similarly, the ACR20 response rate was significantly higher in the peficitinib 100-mg group than in the placebo group (OR: 2.33, 95% CrI: 1.51-3.56). The peficitinib 50-mg group had a significantly higher ACR20 response rate than the placebo group. However, the ACR20 response rate was not significantly higher in the peficitinib 25-mg group than in the placebo group. The ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that peficitinib 150 mg was likely to achieve the best ACR20 response rate (SUCRA = 0.995), followed by peficitinib 100 mg (SUCRA = 0.696), peficitinib 50 mg (SUCRA = 0.558), peficitinib 25 mg (SUCRA = 0.153), and placebo (SUCRA = 0.098). The ACR50 and ACR70 response rates showed a similar distribution pattern to the ACR20 response rate. The difference in the number of patients with adverse events (AEs) among the intervention groups was not statistically significant. CONCLUSIONS:Peficitinib 50, 100, and 150 mg once daily was effective in treating active RA, without causing a significant risk for AEs.
背景和目的: Peficitinib是一种JAK3-selective抑制剂，可阻断信号转导，进而抑制免疫反应，已被用于治疗中重度活动性类风湿关节炎 (RA) 患者。我们评估了在活动期RA患者中每日一次服用培菲尼替尼 (一种JAK3-selective抑制剂) 25 mg、 50 mg、 100 mg和 150 mg的相对疗效和安全性。 方法: 对符合条件的随机对照试验 (rct) 的直接和间接证据进行贝叶斯网络荟萃分析。使用MEDLINE、Embase和Cochrane对照试验注册进行了截至 2019 年 5 月的文献检索。 结果: 3 个rct共 948 例患者符合纳入标准。进行了 10 次成对比较，包括 5 次直接比较和 5 次干预。美国风湿病学会 20% (ACR20) 反应率在 150-mg培菲尼组显著高于安慰剂组 (比值比 (OR): 3.61; 95% 可信区间 (CrI): 2.35-5.57)。同样，peficitinib 100-mg组的ACR20 反应率显著高于安慰剂组 (OR: 2.33，95% CrI: 1.51-3.56)。Peficitinib 50-mg组的ACR20 应答率显著高于安慰剂组。然而，与安慰剂组相比，peficitinib 25-mg组的ACR20 应答率并没有显著升高。基于累积排序曲线下表面的排序概率 (SUCRA) 表明，peficitinib 150 mg可能达到最佳ACR20 应答率 (SUCRA = 0.995)，其次为培菲替尼 100 mg (SUCRA = 0.696)，培菲替尼 50 mg (SUCRA = 0.558)，培菲替尼 25 mg (SUCRA = 0.153)，和安慰剂 (SUCRA = 0.098)。ACR50 和ACR70 应答率表现出与ACR20 应答率相似的分布模式。干预组中发生不良事件 (AEs) 的患者数量差异无统计学意义。 结论: Peficitinib 50 、 100 和 150 mg，每日 1 次，可有效治疗活动性RA，而不会导致ae的显著风险。
METHODS:OBJECTIVE:Patients with immune-mediated inflammatory diseases such as rheumatoid arthritis or systemic lupus erythematosus are at increased risk of cardiovascular disease. However, the cardiovascular risk of patients with primary Sjögren's syndrome (SS) remains poorly studied. We aimed to investigate the association between primary SS and cardiovascular morbidity and mortality. METHODS:We performed a systematic review of articles in Medline and the Cochrane Library and recent abstracts from US and European meetings, searching for reports of randomized controlled studies of cardiovascular morbidity and cardiovascular mortality in primary SS. The relative risk (RR) values for cardiovascular morbidity and mortality associated with primary SS were collected and pooled in a meta-analysis with a random-effects model by using Review Manager (Cochrane collaboration). RESULTS:The literature search revealed 484 articles and abstracts of interest; 14 studies (67,124 patients with primary SS) were included in the meta-analysis. With primary SS versus control populations, the risk was significantly increased for coronary morbidity (RR 1.34 [95% confidence interval (95% CI) 1.06-1.38]; P = 0.01), cerebrovascular morbidity (RR 1.46 [95% CI 1.43-1.49]; P < 0.00001), heart failure rate (odds ratio 2.54 [95% CI 1.30-4.97]; P < 0.007), and thromboembolic morbidity (RR 1.78 [95% CI 1.41-2.25]; P < 0.00001), with no statistically significant increased risk of cardiovascular mortality (RR 1.48 [95% CI 0.77-2.85]; P = 0.24). CONCLUSION:This meta-analysis demonstrates that primary SS is associated with increased cardiovascular morbidity, which suggests that these patients should be screened for cardiovascular comorbidities and considered for preventive interventions, in a multidisciplinary approach with cardiologists.
METHODS:OBJECTIVE:We aimed to evaluate the comparative risk of hospitalized infection among patients with rheumatoid arthritis (RA) who initiated abatacept versus a tumor necrosis factor inhibitor (TNFi). METHODS:Using claims data from Truven MarketScan database (2006-2015), we identified patients with RA ages ≥18 years with ≥2 RA diagnoses who initiated treatment with abatacept or a TNFi. The primary outcome was a composite end point of any hospitalized infection. Secondary outcomes included bacterial infection, herpes zoster, and infections affecting different organ systems. We performed 1:1 propensity score (PS) matching between the groups in order to control for baseline confounders. We estimated incidence rates (IRs) and hazard ratios (HRs) with 95% confidence intervals (95% CIs) for hospitalized infection. RESULTS:We identified 11,248 PS-matched pairs of patients who initiated treatment with abatacept and TNFi with a median age of 56 years (83% were women). The IR per 1,000 person-years for any hospitalized infection was 37 among patients who initiated treatment with abatacept and 47 in those who initiated treatment with TNFi. The HR for the risk of any hospitalized infection associated with abatacept versus TNFi was 0.78 (95% CI 0.64-0.95) and remained lower when compared to infliximab (HR 0.63 [95% CI 0.47-0.85]), while no significant difference was seen when compared to adalimumab and etanercept. The risk of secondary outcomes was lower for abatacept for pulmonary infections, and similar to TNFi for the remaining outcomes. CONCLUSION:In this large cohort of patients with RA who initiated treatment with abatacept or TNFi as a first- or second-line biologic agent, we found a lower risk of hospitalized infection after initiating abatacept versus TNFi, which was driven mostly by infliximab.
METHODS:OBJECTIVE:Reducing pain is one of the main health priorities for children and young people with juvenile idiopathic arthritis (JIA); however, some studies indicate that pain is not routinely assessed in this patient group. The aim of this study was to explore health care professionals' (HCPs) beliefs about the role of pain and the prioritization of its assessment in children and young people with JIA. METHODS:Semi-structured interviews were conducted with HCPs who manage children and young people with JIA in the UK (including consultant and trainee pediatric rheumatologists, nurses, physical therapists, and occupational therapists). Data were analyzed qualitatively following a framework analysis approach. RESULTS:Twenty-one HCPs participated. Analyses of the data identified 6 themes, including lack of training and low confidence in pain assessment, reluctance to engage in pain discussions, low prioritization of pain assessment, specific beliefs about the nature of pain in JIA, treatment of pain in JIA, and undervaluing pain reports. Assessment of pain symptoms was regarded as a low priority and some HCPs actively avoided conversations about pain. CONCLUSION:These findings indicate that the assessment of pain in children and young people with JIA may be limited by knowledge, skills, and attitudinal factors. HCPs' accounts of their beliefs about pain in JIA and their low prioritization of pain in clinical practice suggest that a shift in perceptions about pain management may be helpful for professionals managing children and young people with this condition.