Sint Maartenskliniek, Nijmegen, The Netherlands.
Sint Maartenskliniek and Radboud University Medical Center, Nijmegen, The Netherlands, and Maastricht University Medical Center, Maastricht, The Netherlands.
Arthritis Rheumatol. 2018 Sep;70(9):1408-1418. doi: 10.1002/art.40516. Epub 2018 Aug 6.
To evaluate the effects of non-mandatory transitioning from the originator biologic drug etanercept (ETN) to its biosimilar, SB4, on drug survival and effectiveness in a controlled cohort study of patients with an inflammatory rheumatic disease.
In 2016, 642 patients were asked to transition their treatment from originator ETN to biosimilar SB4 by a structured communication strategy with opt-out option. Patients who consented to switch to SB4 were considered eligible for inclusion in the transition cohort, while patients being treated with originator ETN in 2014 were recruited as the historical cohort. Drug survival was compared between the 2 cohorts using Cox regression analyses, which were adjusted for age, sex, diagnosis, ETN treatment duration, ETN dose interval, conventional synthetic disease-modifying antirheumatic drug usage, and C-reactive protein (CRP) level, with a robust variance estimator applied to account for repeated subjects (i.e., patients who were included in both the transition cohort and the historical cohort). Adjusted differences in the 6-month change in CRP level, Disease Activity Score in 28 joints using CRP level (DAS28-CRP), and Bath Ankylosing Spondylitis Disease Activity Index were also assessed.
Of the 642 ETN-treated patients, 635 (99%) agreed to transition from originator ETN to biosimilar SB4, of whom 625 patients (433 with rheumatoid arthritis, 128 with psoriatic arthritis, and 64 with ankylosing spondylitis) were included in the transition cohort, and 600 ETN-treated patients from 2014 were included in the historical cohort. The crude treatment persistence rate for biosimilar SB4 over 6 months was 90% (95% confidence interval [95% CI] 88-93%), compared to a 6-month treatment persistence rate of 92% (95% CI 90-94%) for originator ETN. Patients in the transition cohort, compared to the historical cohort, had a statistically significantly higher relative risk of treatment discontinuation (adjusted hazard ratio 1.57, 95% CI 1.05-2.36) and showed smaller decreases in the CRP level (adjusted difference 1.8, 95% CI 0.3-3.2) and DAS28-CRP (adjusted difference 0.15, 95% CI 0.05-0.25) over 6 months.
Non-mandatory transitioning from originator ETN to biosimilar SB4 using a specifically designed communication strategy resulted in a slightly lower 6-month treatment persistence rate and smaller decreases in disease activity in the transition cohort compared to the historical cohort, but these differences were not considered clinically relevant.
在一项对炎性风湿病患者的对照队列研究中，评估将生物仿制药依那西普（ETN）从原始药物过渡到其生物类似药 SB4 对药物存活率和疗效的影响。
2016 年，642 名患者被要求通过结构化的沟通策略（带有选择退出选项）将他们的治疗从原始 ETN 过渡到生物类似药 SB4。同意转换为 SB4 的患者被认为符合纳入转换队列的条件，而在 2014 年接受原始 ETN 治疗的患者被招募为历史队列。使用 Cox 回归分析比较了两个队列之间的药物存活率，该分析调整了年龄、性别、诊断、ETN 治疗持续时间、ETN 剂量间隔、常规合成疾病修饰抗风湿药物使用和 C 反应蛋白（CRP）水平，采用稳健方差估计来考虑重复的受试者（即同时被纳入转换队列和历史队列的患者）。还评估了 6 个月时 CRP 水平变化、使用 CRP 水平的 28 个关节疾病活动评分（DAS28-CRP）和 Bath 强直性脊柱炎疾病活动指数的 6 个月变化的调整差异。
在 642 名接受 ETN 治疗的患者中，有 635 名（99%）同意从原始 ETN 过渡到生物类似药 SB4，其中 625 名患者（433 名患有类风湿关节炎、128 名患有银屑病关节炎和 64 名患有强直性脊柱炎）被纳入转换队列，而 600 名 ETN 治疗患者于 2014 年被纳入历史队列。生物类似药 SB4 在 6 个月内的治疗持续率为 90%（95%置信区间[95%CI]88-93%），而原始 ETN 的 6 个月治疗持续率为 92%（95%CI 90-94%）。与历史队列相比，转换队列中的患者停药的相对风险更高（调整后的危险比为 1.57，95%CI 1.05-2.36），并且在 6 个月内 CRP 水平（调整后的差异为 1.8，95%CI 0.3-3.2）和 DAS28-CRP（调整后的差异为 0.15，95%CI 0.05-0.25）的下降幅度较小。
使用专门设计的沟通策略，从原始 ETN 到生物类似药 SB4 的非强制性转换导致转换队列的 6 个月治疗持续率略低，疾病活动度降低幅度小于历史队列，但这些差异被认为无临床意义。
