A head-to-head comparison of the efficacy and safety of ixekizumab and adalimumab in biological-naïve patients with active psoriatic arthritis: 24-week results of a randomised, open-label, blinded-assessor trial.
Ixekizumab和adalimumab在生物初治的活动性银屑病关节炎患者中的疗效和安全性的头对头比较: 随机、开放标签的 24 周结果，盲-评估员试验。
- 作者列表："Mease PJ","Smolen JS","Behrens F","Nash P","Liu Leage S","Li L","Tahir H","Gooderham M","Krishnan E","Liu-Seifert H","Emery P","Pillai SG","Helliwell PS","SPIRIT H2H study group.
OBJECTIVES:To compare efficacy and safety of ixekizumab (IXE) to adalimumab (ADA) in biological disease-modifying antirheumatic drug-naïve patients with both active psoriatic arthritis (PsA) and skin disease and inadequate response to conventional synthetic disease-modifying antirheumatic drug (csDMARDs). METHODS:Patients with active PsA were randomised (1:1) to approved dosing of IXE or ADA in an open-label, head-to-head, blinded assessor clinical trial. The primary objective was to evaluate whether IXE was superior to ADA at week 24 for simultaneous achievement of a ≥50% improvement from baseline in the American College of Rheumatology criteria (ACR50) and a 100% improvement from baseline in the Psoriasis Area and Severity Index (PASI100). Major secondary objectives, also at week 24, were to evaluate whether IXE was: (1) non-inferior to ADA for achievement of ACR50 and (2) superior to ADA for PASI100 response. Additional PsA, skin, treat-to-target and quality-of-life outcome measures were assessed at week 24. RESULTS:The primary efficacy endpoint was met (IXE: 36%, ADA: 28%; p=0.036). IXE was non-inferior for ACR50 response (IXE: 51%, ADA: 47%; treatment difference: 3.9%) and superior for PASI100 response (IXE: 60%, ADA: 47%; p=0.001). IXE had greater response versus ADA in additional PsA, skin, nail, treat-to-target and quality-of-life outcomes. Serious adverse events were reported in 8.5% (ADA) and 3.5% (IXE) of patients. CONCLUSIONS:IXE was superior to ADA in achievement of simultaneous improvement of joint and skin disease (ACR50 and PASI100) in patients with PsA and inadequate response to csDMARDs. Safety and tolerability for both biologicals were aligned with established safety profiles.
目的: 比较ixekizumab (IXE) 与adalimumab (ADA) 在两种活动性银屑病关节炎 (PsA) 的生物修饰疾病抗风湿药物初治患者中的疗效和安全性。和皮肤病和对常规合成疾病修饰抗风湿药 (csDMARDs) 的反应不足。 方法: 在一项开放标签、头对头、盲法评估或临床试验中，将活性PsA患者随机 (1:1) 给予批准剂量的IXE或ADA。主要目的是评估在 24 周时，在美国风湿病学会标准 (ACR50) 中，IXE是否优于ADA同时实现基线 ≥ 50% 的改善银屑病面积和严重程度指数 (PASI100) 较基线改善 100%。同样在第 24 周，主要次要目标是评估IXE是否 :( 1) ACR50 的成就不劣于ADA，(2) PASI100 的反应优于ADA。在第 24 周评估额外的PsA、皮肤、治疗对目标和生活质量结局指标。 结果: 主要疗效终点得到满足 (IXE: 36%，ADA: 28%; p = 0.036)。IXE对ACR50 反应非劣效 (IXE: 51%，ADA: 47%; 治疗差异: 3.9%)，对PASI100 反应优越 (IXE: 60%，ADA: 47%; p = 0.001)。IXE在额外的PsA、皮肤、指甲、治疗目标和生活质量结果方面的反应高于ADA。8.5% (ADA) 和 3.5% (IXE) 的患者报告了严重不良事件。 结论: 在PsA和对csDMARDs反应不足的患者中，IXE在同时改善关节和皮肤病 (ACR50 和PASI100) 方面优于ADA。两种生物制品的安全性和耐受性均与既定的安全性特征一致。
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.