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Janus 激酶抑制剂治疗应答不足的类风湿关节炎患者中加用甲氨蝶呤或依那西普的疗效:ANSWER 队列研究。

Add-on effectiveness of methotrexate or iguratimod in patients with rheumatoid arthritis exhibiting an inadequate response to Janus kinase inhibitors: The ANSWER cohort study.

机构信息

Department of Musculoskeletal Regenerative Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.

Department of Rheumatology, Nishinomiya Municipal Hospital, Hyogo, Japan.

出版信息

Mod Rheumatol. 2023 Jul 4;33(4):690-699. doi: 10.1093/mr/roac092.

Abstract

OBJECTIVES

This multicenter, retrospective study evaluated the effectiveness of add-on methotrexate (MTX) or iguratimod (IGU) in patients with rheumatoid arthritis exhibiting an inadequate response to Janus kinase inhibitors (JAKis).

METHODS

Forty-five patients were treated with new additional MTX (n = 22) or IGU (n = 23) and followed for 6 months. Patients' background is as follows: age, 59.2 years; disease activity score of 28 joints with C-reactive protein (DAS28-CRP), 3.4; clinical disease activity index, 15.7; biological disease-modifying antirheumatic drug (DMARD)-switched cases, 77.8%; first JAKi cases, 95.6%; and JAKi treatment: tofacitinib (n = 25), baricitinib (n = 17), upadacitinib (n = 2), and peficitinib (n = 1) for 9.6 months.

RESULTS

Thirty-five patients continued the combination therapy for 6 months without a significant change in concomitant glucocorticoid or other conventional synthetic DMARDs. DAS28-CRP (MTX, 3.6 to 2.6, p < 0.05; IGU, 3.3 to 2.1, p < 0.001) and clinical disease activity index (MTX, 16.7 to 8.8, p < 0.05; IGU, 14.6 to 6.5, p < 0.01) improved significantly from baseline. Using the 2019 European League Against Rheumatism criteria, 45.4% (MTX) and 39.1% (IGU) achieved moderate or good response and 40.9% (MTX) and 39.1% (IGU) achieved American College of Rheumatology 20% improvement criteria.

CONCLUSIONS

Adding MTX or IGU to inadequate responders of JAKi can be considered as a complementary treatment.

摘要

目的

这项多中心回顾性研究评估了在对 Janus 激酶抑制剂(JAKi)反应不足的类风湿关节炎患者中,加用甲氨蝶呤(MTX)或依那西普(IGU)的疗效。

方法

45 例患者接受新的附加 MTX(n=22)或 IGU(n=23)治疗,并随访 6 个月。患者背景如下:年龄 59.2 岁;C 反应蛋白 28 关节疾病活动度评分(DAS28-CRP)3.4;临床疾病活动指数(CDAI)15.7;生物改善病情抗风湿药(DMARD)转换病例 77.8%;首次使用 JAKi 病例 95.6%;JAKi 治疗:托法替布(n=25)、巴瑞替尼(n=17)、乌帕替尼(n=2)和培非替尼(n=1),治疗时间 9.6 个月。

结果

35 例患者继续联合治疗 6 个月,同时糖皮质激素或其他常规合成 DMARD 无显著变化。DAS28-CRP(MTX,从 3.6 降至 2.6,p<0.05;IGU,从 3.3 降至 2.1,p<0.001)和 CDAI(MTX,从 16.7 降至 8.8,p<0.05;IGU,从 14.6 降至 6.5,p<0.01)自基线显著改善。根据 2019 年欧洲抗风湿病联盟标准,45.4%(MTX)和 39.1%(IGU)达到中或高度缓解,40.9%(MTX)和 39.1%(IGU)达到美国风湿病学会 20%改善标准。

结论

在 JAKi 反应不足的患者中加用 MTX 或 IGU 可作为一种补充治疗。

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