Up to 5-year retention of abatacept in Belgian patients with moderate-to-severe rheumatoid arthritis: a sub-analysis of the international, observational ACTION study.
比利时中重度类风湿关节炎患者保留 abatacept 长达 5 年: 国际观察性行动研究的子分析。
- 作者列表："Westhovens R","Connolly SE","Margaux J","Vanden Berghe M","Maertens M","Van den Berghe M","Elbez Y","Chartier M","Baeke F","Robert S","Malaise M
:Favorable efficacy and safety profiles have been demonstrated for abatacept in patients with rheumatoid arthritis (RA) in randomized controlled trials, but these data require validation during long-term follow-ups in routine clinical practice. This study explored long-term safety and retention rates in RA patients treated with intravenous abatacept in the Belgian cohort of the international AbataCepT In rOutiNe clinical practice (ACTION) study (NCT02109666). This non-interventional, observational, longitudinal study included Belgian patients aged ≥ 18 years with moderate-to-severe RA who started intravenous abatacept treatment as first- or second/further-line biologic therapy in routine clinical practice. Between October 2010 and December 2012, 141 patients were enrolled in this cohort, of whom 135 evaluable patients (6 biologic-naïve; 129 previously exposed to ≥ 1 prior biologic disease modifying anti-rheumatic drugs) were eligible for the descriptive analysis; 131/135 were included in the effectiveness analysis. Mean disease duration was 10.5 years (standard deviation 9.7) before abatacept initiation. RA patients presented with high disease activity and comorbidity rate, having failed multiple previous treatment options. In this cohort, the 5-year abatacept retention rate was 34% (95% confidence interval, 23-45%) per protocol, and 51% (95% confidence interval, 40-61%) when temporary discontinuations of abatacept > 84 days (n = 24) were not considered as treatment discontinuations. After 5 years of abatacept treatment, clinical outcomes were favorable [good/moderate European League Against Rheumatism (EULAR) responses in 91.7% patients]. No new safety signals were detected for abatacept in routine clinical practice. In this difficult-to-treat Belgian RA population, high retention rates, good clinical outcomes and favorable safety profile were observed with abatacept.
: 在随机对照试验中，abatacept 在类风湿关节炎 (RA) 患者中的疗效和安全性已被证明,但是这些数据需要在常规临床实践中的长期随访期间进行验证。本研究在国际 abatacept 常规临床实践 (ACTION) 研究 (NCT02109666) 的比利时队列中探讨了静脉注射 AbataCepT 治疗的 RA 患者的长期安全性和保留率。这种非干预性的，观察性的,纵向研究纳入年龄 ≥ 18 岁的中重度 RA 比利时患者，在常规临床实践中开始静脉阿巴西普治疗作为一线或二线/二线生物治疗。2010 年 10 月至 2012 年 12 月，141 例患者入选本队列，其中 135 例可评估患者 (6 例生物初治; 129 例既往接触过 ≥ 1 种生物疾病修饰抗风湿药) 有资格进行描述性分析; 131/135 被纳入有效性分析。Abatacept 开始前平均病程为 10.5 年 (标准差 9.7)。RA 患者表现出较高的疾病活动性和合并症率，既往多个治疗方案均失败。在该队列中，每个方案的 5 年 abatacept 保留率为 34% (95% 置信区间，23-45%)，51% (95% 置信区间，40-61%) 当 abatacept 暂时停药> 84 天 (n = 24) 不被视为治疗停药。经过 5 年的阿巴西普治疗，临床结果良好 [91.7% 例患者的良好/中度欧洲抗风湿病联盟 (EULAR) 反应]。在常规临床实践中未检测到 abatacept 的新安全性信号。在这个难以治疗的比利时 RA 人群中，观察到 abatacept 的高保留率、良好的临床结局和有利的安全性。
METHODS:Rheumatoid arthritis (RA) is an autoimmune disease which can lead to progressive and functional disability. Literature data suggest that some inflammatory proteins are dysregulated in RA patients and its genetic polymorphisms may contribute to the aetiology and pathogenesis of disease in different ethnic groups. Polymorphisms in and genes were studied in different populations with RA, but the analysis indicated contradictory results. Thereby, we hypothesised that polymorphisms in these genes could have a combined effect on susceptibility to and severity of disease. We evaluated the +3953 C/T (rs1143634), -137 G/C (rs187238), -94 ins/del ATTG (rs28362491) and +874 T/A (rs2430561) polymorphisms in the northeastern Brazilian population. Peripheral blood samples were collected and DNA extraction was conducted. The polymorphisms were evaluated by RFLP and ARMS-PCR. An association was observed in rs1143634 which showed a protective effect against development of RA in carriers of the T allele (OR = 0.58; 95% CI 0.36-0.92; = .020). In addition, we found an association among genotypes of the rs1143634 with the HAQ index ( = .021) and rs2430561 with DAS28 ( = .029) and CDAI ( = .029). In relation to combined effects of these SNPs (C/C to rs1143634, G/G to rs187238, I/I to rs28362491 and AA to rs2430561) we found a significant association with decreased functional disability (HAQ index < .001) and ESR ( = .034), indicating a lower disease activity in carriers of these genotypes. GLM analysis confirmed these associations (HAQ ( = 5.497; < .001) and ESR ( = 2.727; = .032)). Our analysis indicated that in the studied population +3953 C/T (rs1143634), -137 G/C (rs187238), -94 ins/del ATTG (rs28362491) and +874 T/A (rs2430561) polymorphisms can together contribute to RA severity although they do not individually influence the disease.
METHODS:ZNF804a and CDK1 genes code for proteins involved in inflammatory pathways. This study aimed to investigate the correlation of ZNF804a and CDK1 expression profiles in RA with the activity and the severity of the disease and to assess their association with inflammatory reactions in the Egyptian RA patients. ZNF804a and CDK1 expression profiles were assessed using quantitative PCR (qRT-PCR). Clinical and laboratory parameters were evaluated. ZNF804a expression was down-regulated by 0.177-fold while CDK1 expression was up-regulated to 3.29-fold in RA patients compared with healthy controls ( < .001). ZNF804a down-regulation was negatively correlated with CRP, RF, disease activity score of 28 joints (DAS) using CRP (DAS-CRP) and TNF-α. CDK1 overexpression was correlated with IFN-1 and ACPA in RA patients. ZNF804a and CDK1 genes are implicated in RA pathogenesis due to their influences on TNF-α and IFN-1 which contribute to inflammation in RA patients.
METHODS:OBJECTIVES:We sought to confirm in very early rheumatoid arthritis (ERA) a much greater superiority (30%) of first-line etanercept+methotrexate (ETN+MTX) over treat-to-target MTX (MTX-TT) than previously reported in ERA (14%); and explore whether ETN following initial MTX secures a comparable response to first-line ETN+MTX. METHODS:Pragmatic, open-label, randomised controlled trial of treatment-naïve ERA (≤12 months symptom), Disease Activity Score 28 joint (DAS28)-erythrocyte sedimentation rate (ESR) ≥3.2, rheumatoid factor (RF)+/-anticitrullinated peptide antibody (ACPA) positive or ultrasound power Doppler (PD) if RF and ACPA negative. Subjects were randomised 1:1 to ETN+MTX; or MTX-TT, escalated to ETN if week 24 DAS28-ESR ≥2.6 and intramuscular corticosteroid at protocolised time points. Primary endpoint of week 48 DAS28ESR remission with clinical and imaging secondary endpoints. RESULTS:We randomised 120 patients, 60 to each arm (71% female, 73% RF/84% ACPA positive, median (IQR) symptom duration 20.3 (13.1, 30.8) weeks; mean (SD) DAS28 5.1 (1.1)). Remission rates with ETN+MTX and MTX-TT, respectively, were 38% vs 33% at week 24; 52% vs 38% at week 48 (ORs 1.6, 95% CI 0.8 to 3.5, p=0.211). Greater, sustained DAS28-ESR remission observed with ETN+MTX versus MTX-TT (42% and 27%, respectively; p=0.035). PD was fully suppressed by week 48 in over 90% in each arm. Planned exploratory analysis revealed OR 2.84, 95% CI 0.8 to 9.6) of achieving remission after 24 weeks of ETN administered first line compared with administered post-MTX. CONCLUSIONS:Compared with remission rates typically reported with first-line tumour necrosis factor inhabitor+MTX versus MTX-TT, we did not demonstrate a larger effect in very ERA. Neither strategy conferred remission in the majority of patients although ultrasound confirmed local inflammation suppression. Poorer ETN response following failure of MTX-TT is also suggested.Trial registration numberNCT02433184.