老年类风湿关节炎患者中七种生物制剂的药物耐受性和停药原因 - ANSWER 队列研究。
Drug tolerability and reasons for discontinuation of seven biologics in elderly patients with rheumatoid arthritis -The ANSWER cohort study.
机构信息
Department of Orthopaedic Surgery, Osaka University, Graduate School of Medicine, Osaka, Japan.
Department of Advanced Medicine for Rheumatic Diseases, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
出版信息
PLoS One. 2019 May 8;14(5):e0216624. doi: 10.1371/journal.pone.0216624. eCollection 2019.
BACKGROUND
The aim of this study is to evaluate the retention rates and reasons for discontinuation for seven biological disease-modifying antirheumatic drugs (bDMARDs) in a real-world setting of elderly patients (65 years of age or older) with rheumatoid arthritis (RA).
METHODS
This multi-center, retrospective study assessed 1,098 treatment courses of 661 patients with bDMARDs from 2009 to 2018 (females, 80.7%; baseline age, 71.7 years; disease duration 10.5 years; rheumatoid factor positivity 81.3%; Disease Activity Score in 28 joints using erythrocyte sedimentation rate, 4.6; concomitant prednisolone dose 2.8 mg/day (45.6%) and methotrexate dose 4.4 mg/week (56.4%); and 60.2% patients were bio-naïve). Treatment courses included abatacept (ABT; n = 272), tocilizumab (TCZ; n = 234), etanercept (ETN; n = 184), golimumab (GLM; n = 159), infliximab (IFX; n = 101), adalimumab (ADA; n = 97), and certolizumab pegol (CZP; n = 51). Drug retention rates and discontinuation reasons were estimated at 36 months using the Kaplan-Meier method and adjusted for potential clinical confounders (age, sex, disease duration, concomitant PSL and MTX, starting date and switched number of bDMARDs) by Cox proportional hazards modeling.
RESULTS
A total of 51.2% of treatment courses were stopped, with 25.1% stopping due to lack of effectiveness, 11.8% due to toxic adverse events, 9.7% due to non-toxic reasons, and 4.6% due to remission. Drug retention rates for each discontinuation reason were as follows; lack of effectiveness [from 55.4% (ETN) to 81.6% (ABT); with significant differences between groups (Cox P<0.001)], toxic adverse events [from 79.3% (IFX) to 95.4% (ABT), Cox P = 0.043], and remission [from 94.2% (TCZ) to 100.0% (CZP), Cox P = 0.58]. Finally, overall retention rates excluding non-toxic reasons and remission for discontinuation ranged from 50.0% (ETN) to 78.1% (ABT) (Cox P<0.001).
CONCLUSIONS
ABT showed lowest discontinuation rate by lack of effectiveness and by toxic adverse events, which lead to highest overall retention rates (excluding non-toxic reasons and remission) among seven bDMARDs in adjusted model of elderly RA patients.
背景
本研究旨在评估七种生物改善病情抗风湿药物（bDMARDs）在老年类风湿关节炎（RA）患者（65 岁及以上）真实世界环境中的保留率和停药原因。
方法
这项多中心、回顾性研究评估了 2009 年至 2018 年期间 661 例患者的 1098 个 bDMARD 治疗疗程（女性，80.7%；基线年龄，71.7 岁；疾病持续时间 10.5 年；类风湿因子阳性率 81.3%；红细胞沉降率 28 关节疾病活动评分，4.6；同时使用泼尼松龙剂量 2.8mg/天（45.6%）和甲氨蝶呤剂量 4.4mg/周（56.4%）；60.2%的患者为生物初治）。治疗疗程包括阿巴西普（ABT；n=272）、托珠单抗（TCZ；n=234）、依那西普（ETN；n=184）、戈利木单抗（GLM；n=159）、英夫利昔单抗（IFX；n=101）、阿达木单抗（ADA；n=97）和培塞利珠单抗（CZP；n=51）。使用 Kaplan-Meier 方法在 36 个月时估计药物保留率和停药原因，并通过 Cox 比例风险建模调整潜在的临床混杂因素（年龄、性别、疾病持续时间、同时使用泼尼松龙和甲氨蝶呤、起始日期和 bDMARDs 的转换数量）进行调整。
结果
共有 51.2%的治疗疗程停止，其中 25.1%因缺乏疗效而停止，11.8%因毒性不良反应而停止，9.7%因非毒性原因而停止，4.6%因缓解而停止。每种停药原因的药物保留率如下：缺乏疗效[从 55.4%（ETN）到 81.6%（ABT）；组间差异有统计学意义（Cox P<0.001）]、毒性不良反应[从 79.3%（IFX）到 95.4%（ABT），Cox P=0.043]和缓解[从 94.2%（TCZ）到 100.0%（CZP），Cox P=0.58]。最后，排除非毒性原因和缓解的总停药率在 50.0%（ETN）到 78.1%（ABT）之间（Cox P<0.001）。
结论
在调整后的老年 RA 患者模型中，ABT 因缺乏疗效和毒性不良反应导致的停药率最低，因此总体保留率（排除非毒性原因和缓解）最高（Cox P<0.001）。
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