Nüßlein Hubert G, Alten Rieke, Galeazzi Mauro, Lorenz Hanns-Martin, Nurmohamed Michael T, Bensen William G, Burmester Gerd R, Peter Hans-Hartmut, Pavelka Karel, Chartier Melanie, Poncet Coralie, Rauch Christiane, Le Bars Manuela
University of Erlangen-Nuremberg, Rheumatologische Schwerpunkpraxis, Kontumazgarten 4, 90429, Nuremberg, Germany.
Schlosspark-Klinik University Medicine, Berlin, Germany.
BMC Musculoskelet Disord. 2015 Jul 30;16:176. doi: 10.1186/s12891-015-0636-9.
The emergence of new therapies for the treatment of rheumatoid arthritis (RA), the paucity of head-to-head studies, and the heterogeneous nature of responses to current biologics highlight the need for the identification of prognostic factors for treatment response and retention in clinical practice. Prognostic factors for patient retention have not been explored thoroughly despite data for abatacept and other biologics being available from national registries. Real-world data from the ACTION study may supplement the findings of randomized controlled trials and show how abatacept is used in clinical practice. The aim of this interim analysis was to identify prognostic factors for abatacept retention in patients with RA who received at least one prior biologic agent.
A large, international, non-interventional cohort of patients with moderate-to-severe RA who initiated intravenous abatacept in Canada and Europe (May 2008-January 2011) enrolled in the ACTION study. Potential prognostic factors for retention in this interim analysis (data cut-off February 2012; including patients from Canada, Germany, Greece, and Italy) were baseline demographics and disease characteristics, medical history, and previous and concomitant medication. Clinically relevant variables with p ≤ 0.20 in univariate analysis and no collinearity were entered into a Cox proportional hazards regression model, adjusted for clustered data. Variables with p ≤ 0.10 were retained in the final model (backward selection).
The multivariate model included 834 patients. Anti-cyclic citrullinated peptide (CCP) antibody positivity (hazard ratio [95% confidence interval]: 0.55 [0.40, 0.75], p < 0.001), failure of <2 prior anti-tumor necrosis factors (TNFs) (0.71 [0.56, 0.90], p = 0.005 versus ≥2 prior anti-TNFs), and cardiovascular comorbidity at abatacept initiation (0.48 [0.28, 0.83], p = 0.009) were associated with lower risk of abatacept discontinuation. Patients in Greece and Italy were less likely to discontinue abatacept than patients in Germany and Canada (Greece: 0.30 [0.16, 0.58]; Italy: 0.50 [0.33, 0.76]; Canada: 1.04 [0.78, 1.40], p < 0.001 versus Germany).
Real-world prognostic factors for abatacept retention include anti-CCP positivity and fewer prior anti-TNF failures. Differences in retention rates between countries may reflect differences in healthcare systems. The finding that abatacept has potential advantages in patients with cardiovascular comorbidities needs to be confirmed in further research.
类风湿关节炎（RA）新疗法的出现、头对头研究的匮乏以及当前生物制剂反应的异质性，凸显了在临床实践中识别治疗反应和持续治疗的预后因素的必要性。尽管国家登记处有阿巴西普和其他生物制剂的数据，但尚未对患者持续治疗的预后因素进行深入研究。ACTION研究的真实世界数据可能会补充随机对照试验的结果，并展示阿巴西普在临床实践中的使用情况。这项中期分析的目的是确定接受过至少一种先前生物制剂治疗的RA患者中阿巴西普持续治疗的预后因素。
一项大型、国际、非干预性队列研究，纳入了在加拿大和欧洲（2008年5月至2011年1月）开始静脉注射阿巴西普的中重度RA患者，这些患者参与了ACTION研究。在这项中期分析（数据截止于2012年2月；包括来自加拿大、德国、希腊和意大利的患者）中，持续治疗的潜在预后因素包括基线人口统计学和疾病特征、病史以及既往和同时使用的药物。单因素分析中p≤0.20且无共线性的临床相关变量被纳入Cox比例风险回归模型，并对聚类数据进行了调整。p≤0.10的变量被保留在最终模型中（向后选择）。
多变量模型纳入了834例患者。抗环瓜氨酸肽（CCP）抗体阳性（风险比[95%置信区间]：0.55[0.40, 0.75]，p<0.001）、既往使用<2种抗肿瘤坏死因子（TNF）失败（0.71[0.56, 0.90]，与≥2种既往抗TNF相比，p = 0.005）以及开始使用阿巴西普时存在心血管合并症（0.48[0.28, 0.83]，p = 0.009）与阿巴西普停药风险较低相关。希腊和意大利的患者比德国和加拿大的患者更不容易停用阿巴西普（希腊：0.30[0.16, 0.58]；意大利：0.50[0.33, 0.76]；加拿大：1.04[0.78, 1.40]，与德国相比，p<0.001）。
阿巴西普持续治疗的真实世界预后因素包括抗CCP阳性和既往抗TNF失败次数较少。各国持续治疗率的差异可能反映了医疗保健系统的差异。阿巴西普在有心血管合并症的患者中具有潜在优势这一发现需要在进一步研究中得到证实。
