Evaluation of the Short-, Mid-, and Long-Term Effects of Tofacitinib on Lymphocytes in Patients With Rheumatoid Arthritis
Evaluation of the Short-, Mid-, and Long-Term Effects of Tofacitinib on Lymphocytes in Patients With Rheumatoid Arthritis
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DOI：
10.1002/art.40780
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发表时间：
2019-05-01
影响因子：
13.3
通讯作者：
Choy, Ernest
中科院分区：
文献类型：
--
作者：
van Vollenhoven, Ronald;Lee, Eun Bong;Choy, Ernest
目的托法替尼是一种口服JAK抑制剂，用于治疗类风湿关节炎(RA)。据报道，在接受JAK抑制剂治疗的RA患者中，淋巴细胞计数的改变以及与感染率增加的潜在关联。这项分析是为了评估托法替尼对RA患者淋巴细胞和感染率的短期、中期和长期影响。方法在这项后组分析中，绝对淋巴细胞计数(ALCS)来自托法替尼的III期研究(12-24个月；n=717-958)和I/II/III/长期推广研究(117个月)(所有RA人群；n=7,061)；淋巴细胞亚群(LSC)来自II期研究(1.5-6个月暴露；n=236-486)，口服续发疫苗亚研究(类似于22个月；N=198)，以及托法替尼的口服后续淋巴细胞亚研究(类似于50个月；n=55-1,035)。评价ALC/LSC变化的可逆性。分析ALC和LSC与RA感染的关系。通过检验ALC和LSC之间的相关性来评估单独监测ALC的价值。结果托法替尼治疗后ALC最初较治疗前升高，在大约48个月后逐渐下降至稳定状态。在长期治疗期间，CD4+和CD8+T细胞计数下降，ALC和LSC的变化在治疗停止后是可逆的。肌萎缩侧索硬化患者
ObjectiveTofacitinib is an oral JAK inhibitor for the treatment of rheumatoid arthritis (RA). Altered lymphocyte cell counts and a potential association with increased infection rates have been reported in RA patients treated with JAK inhibitors. This analysis was undertaken to evaluate the short-, mid-, and long-term effects of tofacitinib on lymphocytes and infection rates in patients with RA.MethodsIn this post hoc analysis, absolute lymphocyte counts (ALCs) were obtained from phase III studies (12-24 months; n = 717-958) and phase I/II/III/long-term extension studies of tofacitinib (117 months) (All RA population; n = 7,061); lymphocyte subset counts (LSCs) were from phase II studies (1.5-6 months' exposure; n = 236-486), an ORAL Sequel vaccine substudy (similar to 22 months; n = 198), and an ORAL Sequel lymphocyte substudy (similar to 50 months; n = 55-1,035) of tofacitinib. The reversibility of ALC/LSC changes was evaluated. The relationship of ALC and LSC to infections was analyzed in the All RA population. The value of monitoring ALC alone was assessed by examining correlations between ALCs and LSCs.ResultsTofacitinib treatment resulted in an initial increase in ALC versus pretreatment baseline, which gradually declined to steady state by similar to 48 months. CD4+ and CD8+ T cell counts decreased over long-term treatment, and ALC and LSC changes were reversible upon treatment cessation. Patients with ALCs of