Abuhelwa Ahmad Y, Foster David J R, Manning-Bennett Arkady, Sorich Michael J, Proudman Susanna, Wiese Michael D, Hopkins Ashley M
Discipline of Clinical Pharmacology, College of Medicine and Public Health, Flinders University, Sturt Rd, Bedford Park, SA 5042, Australia.
Health and Biomedical Innovation, UniSA: Clinical and Health Sciences, University of South Australia, Adelaide, SA Australia.
Ther Adv Musculoskelet Dis. 2021 Apr 12;13:1759720X211009020. doi: 10.1177/1759720X211009020. eCollection 2021.
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease associated with increased risk of cardiovascular disease (CVD). Treatment for CVD may involve pharmacological agents that antagonise beta adrenergic receptors. These receptors may play an important role in immunology, and the effects of beta-blockers (BB) in RA is unknown. The aim of this study was to investigate the association between BB use and remission in patients with RA initiating tocilizumab +/- conventional synthetic (cs-) DMARD therapy.
Data was pooled from five randomised trials investigating tocilizumab and/or csDMARD treatment in RA (primarily methotrexate). The association between BB use and remission according to the Simplified Disease Activity Index (SDAI) and Clinical Disease Activity Index (CDAI) was assessed by Cox proportional hazard analysis. Sensitivity analysis in patients with pre-existing CVD and an exploratory analysis of the impact of other CVD drugs were conducted.
Data were available from 5502 participants, 594 (10.8%) of whom were using systemic BB. BB use was associated with less frequent SDAI remission in the total [adjusted hazard ratio (HR) 0.70, 95% confidence interval (CI) 0.57-0.87, = 0.001] and CVD cohort [adjusted HR 0.72 (0.57-0.90, = 0.005)]. The association was consistent between trials (interaction = 0.44) and treatment arms (interaction = 0.06). No significant association between remission and β1-receptor selectivity was identified ( = 0.16), and the association was independent from other cardiovascular drug use. Similar associations between BB use and CDAI remission were observed.
In a large, pooled cohort of RA patients initiating csDMARDs and/or tocilizumab, BB use was independently associated with less frequent remission.
类风湿关节炎(RA)是一种慢性炎症性自身免疫性疾病,与心血管疾病(CVD)风险增加相关。CVD的治疗可能涉及拮抗β肾上腺素能受体的药物。这些受体可能在免疫学中起重要作用,而β受体阻滞剂(BB)在RA中的作用尚不清楚。本研究的目的是调查开始使用托珠单抗±传统合成(cs-)改善病情抗风湿药(DMARD)治疗的RA患者中使用BB与病情缓解之间的关联。
汇总了五项关于托珠单抗和/或csDMARD治疗RA(主要是甲氨蝶呤)的随机试验数据。根据简化疾病活动指数(SDAI)和临床疾病活动指数(CDAI),通过Cox比例风险分析评估使用BB与病情缓解之间的关联。对已有CVD的患者进行了敏感性分析,并对其他CVD药物的影响进行了探索性分析。
共有5502名参与者的数据,其中594名(10.8%)正在使用全身性BB。在总队列[调整后风险比(HR)0.70,95%置信区间(CI)0.57-0.87,P=0.001]和CVD队列[调整后HR 0.72(0.57-0.90,P=0.005)]中,使用BB与SDAI缓解频率较低相关。试验之间(交互作用P=0.44)和治疗组之间(交互作用P=0.06)的关联是一致的。未发现缓解与β1受体选择性之间存在显著关联(P=0.16),且该关联独立于其他心血管药物的使用。观察到使用BB与CDAI缓解之间存在类似关联。
在一大组开始使用csDMARD和/或托珠单抗的RA患者队列中,使用BB与缓解频率较低独立相关。