Temmoku Jumpei, Miyata Masayuki, Suzuki Eiji, Sumichika Yuya, Saito Kenji, Yoshida Shuhei, Matsumoto Haruki, Fujita Yuya, Matsuoka Naoki, Asano Tomoyuki, Sato Shuzo, Watanabe Hiroshi, Migita Kiyoshi
Department of Rheumatology, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima 960-1295, Fukushima, Japan.
Department of Rheumatology, Japanese Red Cross Fukushima Hospital, Yashima 7-7, Fukushima 963-8558, Fukushima, Japan.
J Clin Med. 2023 Jul 21;12(14):4827. doi: 10.3390/jcm12144827.
To determine whether drug-induced lymphocytopenia is associated with drug retention rates of JAKi (tofacitinib or baricitinib) in rheumatoid arthritis (RA) patients.
Patients with RA who were initiated with tofacitinib ( = 38) or baricitinib ( = 74) between July 2015 and July 2022 and continued for at least 4 months were enrolled in this study. Absolute lymphocyte count (ALC) value was obtained pre-treatment and monthly after initiation of JAKi (up to 4 months). Associations between ALC nadir at an early phase (up to 4 months) from JAKi initiation and drug retention rates were analysed.
112 patients (87 females; age, 71.2 ± 14.0 years; disease duration, 9.2 ± 10.5 months; DAS28-CRP, 3.60 ± 1.12; DAS28-ESR, 4.43 ± 1.29; CDAI, 17.9 ± 12.9; C-reactive protein, 3.07 ± 3.43 mg/dL; and lymphocyte count, 1361.9 ± 538.7 per μL) treated with tofacitinib or baricitinib were retrospectively analysed. Lymphocytopenia (>10% decline in lymphocyte count to pre-treatment basal levels) was observed in a quarter of RA patients treated with JAKi (tofacitinib; 16 baricitinib; 14). RA patients with lymphopenia were associated with the lower drug retention rates of tofacitinib compared to those without lymphocytopenia. The reduced drug retention rates in patients with lymphocytopenia were attributed to the discontinuation of tofacitinib due to AEs. Whereas lymphocytopenia was not associated with lower drug retention rates of baricitinib. Pre-treatment absolute lymphocyte counts did not affect the drug retention rates of JAKi in patients with RA.
These findings suggest that lymphopenia during the first 4 months from the initiation of JAKi is associated with reduced drug retention rates in patients with RA due to AEs, which is exclusively associated with the use of tofacitinib.
确定药物性淋巴细胞减少症是否与类风湿关节炎(RA)患者中JAK抑制剂(托法替布或巴瑞替尼)的药物留存率相关。
本研究纳入了2015年7月至2022年7月期间开始使用托法替布(n = 38)或巴瑞替尼(n = 74)且持续用药至少4个月的RA患者。在开始使用JAK抑制剂前及开始用药后每月(最长4个月)获取绝对淋巴细胞计数(ALC)值。分析了JAK抑制剂开始使用后早期(最长4个月)的ALC最低点与药物留存率之间的关联。
对112例接受托法替布或巴瑞替尼治疗的患者(87例女性;年龄71.2±14.0岁;病程9.2±10.5个月;DAS28-CRP 3.60±1.12;DAS28-ESR 4.43±1.29;CDAI 17.9±12.9;C反应蛋白3.07±3.43mg/dL;淋巴细胞计数1361.9±538.7/μL)进行了回顾性分析。在接受JAK抑制剂治疗的RA患者中,四分之一出现了淋巴细胞减少症(淋巴细胞计数较治疗前基础水平下降>10%)(托法替布组16例;巴瑞替尼组14例)。与无淋巴细胞减少症的患者相比,淋巴细胞减少的RA患者中托法替布的药物留存率较低。淋巴细胞减少症患者药物留存率降低归因于因不良事件停用托法替布。而淋巴细胞减少症与巴瑞替尼较低的药物留存率无关。治疗前绝对淋巴细胞计数不影响RA患者中JAK抑制剂的药物留存率。
这些发现表明,JAK抑制剂开始使用后的前4个月内出现的淋巴细胞减少症与RA患者因不良事件导致的药物留存率降低相关,这仅与托法替布的使用有关。