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真实世界中单中心使用 JAK 抑制剂治疗类风湿关节炎。

Real-world single centre use of JAK inhibitors across the rheumatoid arthritis pathway.

机构信息

Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Chapel Allerton Hospital, Leeds, UK.

NIHR Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Chapel Allerton Hospital, Leeds, UK.

出版信息

Rheumatology (Oxford). 2021 Sep 1;60(9):4048-4054. doi: 10.1093/rheumatology/keaa858.

Abstract

OBJECTIVES

To evaluate real-world efficacy of approved JAK inhibitors (JAKi) tofacitinib and baricitinib in a large, single-centre cohort of RA patients across the treatment pathway, including those refractory to multiple biologic drugs.

METHODS

All RA patients, treated with tofacitinib (from time of compassionate access scheme) or baricitinib since approval in 2017 had DAS28-CRP scores and components recorded at baseline, 3 and 6 months (with retrospective data for compassionate access scheme). Efficacy was evaluated in the total cohort, each treatment group, and subgroups of number of prior biologic classes failed.

RESULTS

One hundred and fifteen patients were treated with a JAKi (tofacitinib 54, baricitinib 69, 8 both); 76.4% female; mean (s.d.) age 57.3 (14.3) years. On average patients had received three previous bDMARDs; 11 (9.6%) were bDMARD naïve. Combined group baseline DAS28-CRP (s.d.) 5.62(1.14) improved by 1.49(1.44) and 1.67(1.61) at 3 and 6 months, respectively, comparable in individual JAKi groups; with 24% in at least low disease activity at 3 months. The biggest improvement was observed in the biologic-naïve group (mean DAS28-CRP improved from 5.16-2.14 after 6 months); while those with prior exposure to minimum three bDMARD classes had DAS28-CRP improvement of >1.2. Five out of 8 patients treated with both JAKi sequentially responded. Twelve patients previously unresponsive to IL-6 blockade responded to JAKi. No unexpected safety events were recorded. Two cases of venous thromboembolism were observed.

CONCLUSION

JAK inhibition is effective in a real-world population of RA patients, including in a subset of patients refractory to multiple previous bDMARDs.

摘要

目的

评估获批的 JAK 抑制剂(JAKi)托法替布和巴瑞替尼在一个大型单中心 RA 患者治疗路径中的真实世界疗效,包括那些对多种生物药物难治的患者。

方法

所有自 2017 年获批以来接受托法替布(从同情准入计划开始)或巴瑞替尼治疗的 RA 患者,均记录了 DAS28-CRP 评分和基线、3 个月和 6 个月时的各项指标(对于同情准入计划,有回顾性数据)。在总队列、每个治疗组和既往生物制剂失败次数亚组中评估疗效。

结果

115 例患者接受了 JAKi 治疗(托法替布 54 例,巴瑞替尼 69 例,8 例两者均用);76.4%为女性;平均(标准差)年龄 57.3(14.3)岁。平均每位患者接受了三种以上的前生物制剂治疗;11 例(9.6%)为生物制剂初治。联合组基线 DAS28-CRP(标准差)5.62(1.14)分别改善了 1.49(1.44)和 1.67(1.61),在单个 JAKi 组中具有可比性;3 个月时有 24%患者达到至少低疾病活动度。在生物制剂初治组观察到最大的改善(平均 DAS28-CRP 在 6 个月后从 5.16 降至 2.14);而那些曾接触过至少三种生物制剂类别的患者,DAS28-CRP 改善>1.2。8 例接受两种 JAKi 序贯治疗的患者中有 5 例有反应。12 例先前对 IL-6 阻断剂无反应的患者对 JAKi 有反应。未记录到意外的安全事件。观察到两例静脉血栓栓塞事件。

结论

JAK 抑制在 RA 患者的真实世界人群中是有效的,包括对多种先前生物制剂难治的患者。

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