Risk for Herpes Zoster in Tofacitinib-Treated Rheumatoid Arthritis Patients With and Without Concomitant Methotrexate and Glucocorticoids
Risk for Herpes Zoster in Tofacitinib-Treated Rheumatoid Arthritis Patients With and Without Concomitant Methotrexate and Glucocorticoids
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DOI：
10.1002/acr.23769
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发表时间：
2019-07-29
影响因子：
4.7
通讯作者：
Winthrop, Kevin
中科院分区：
文献类型：
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作者：
Curtis, Jeffrey R.;Xie, Fenglong;Winthrop, Kevin
目的 观察到托法替布等 JAK 抑制剂会增加带状疱疹 (HZ) 的发病率。然而，同时使用甲氨蝶呤（MTX）和/或糖皮质激素是否会带来额外（加性或乘性）风险尚不清楚。我们评估了使用或不使用 MTX 和糖皮质激素的托法替布使用者的带状疱疹风险。方法 在 MarketScan 和 Medicare 数据（2011-2016）中，我们确定了所有经风湿病学家诊断为类风湿性关节炎且开始接受托法替布治疗的患者（索引日期）；人口统计数据和基线协变量在指数日期之前的一年进行了评估。使用国际疾病分类第九版或第十版代码并使用抗病毒药物（+/- 7 天）来确定带状疱疹。多变量 Cox 回归用于评估托法替布使用者在使用或不使用 MTX 和糖皮质激素的情况下 HZ 的风险比 (HR)，并控制基线协变量。结果 我们研究了 8,030 名托法替尼新使用者（83.3% 为女性）。平均 +/- SD 年龄为 60.3 +/- 12.6 岁。在不使用糖皮质激素的情况下，托法替布使用者的带状疱疹发生率最低（使用 MTX 时每 100 患者年 3.4 例；不使用 MTX 时每 100 患者年 3.7 例）。对于单独接受糖皮质激素（每 100 名患者年 6.0 例）或接受 MTX 加糖皮质激素（每 100 名患者年 6.5 例）的托法替布使用者，观察到带状疱疹的发生率增加了约 2 倍。当仅与 MTX 联合用药时，托法替布使用者 HZ 的调整后 HR 没有变化（HR 0.99 [95% 置信区间 (95% CI) 0.64-1.54]），但托法替布联合糖皮质激素则增加（HR 1.96 [95% CI 1.33-2.88]）。年龄较大和女性也是危险因素，而先前接种疫苗与风险较低的强烈趋势相关。结论 在托法替布使用者中，带状疱疹的发生率约为每年 4%，并且随着糖皮质激素的暴露而进一步加倍。联合使用 MTX 不会带来额外的风险。带状疱疹疫苗接种可能会降低风险。
Objective Increased incidence of herpes zoster (HZ) has been observed with JAK inhibitors such as tofacitinib. However, whether concomitant methotrexate (MTX) and/or glucocorticoids confer additional (additive or multiplicative) risk is unclear. We evaluated HZ risk in tofacitinib users with and without MTX and glucocorticoids. Methods Within MarketScan and Medicare data (2011-2016), we identified all patients with rheumatologist-diagnosed rheumatoid arthritis initiating treatment with tofacitinib (index date); demographics and baseline covariates were evaluated in the year prior to the index date. HZ was ascertained using International Classification of Diseases, Ninth Revision or Tenth Revision codes with antiviral drug use (+/- 7 days). Multivariable Cox regression was used to evaluate hazard ratios (HRs) for HZ in tofacitinib users with and without current concomitant MTX and glucocorticoids, controlling for baseline covariates. Results We studied 8,030 new tofacitinib users (83.3% women). The mean +/- SD age was 60.3 +/- 12.6 years. HZ incidence in tofacitinib users was numerically lowest in the absence of glucocorticoids (3.4 per 100 patient-years with MTX; 3.7 per 100 patient-years without MTX). An approximately 2-fold increased incidence of HZ was observed for tofacitinib users receiving either glucocorticoids alone (6.0 per 100 patient-years) or both MTX plus glucocorticoids (6.5 per 100 patient-years). The adjusted HR for HZ in tofacitinib users was unchanged (HR 0.99 [95% confidence interval (95% CI) 0.64-1.54]) when given only with MTX, but was increased (HR 1.96 [95% CI 1.33-2.88]) for tofacitinib plus glucocorticoids. Older age and female sex were also risk factors, while prior vaccination was associated with a strong trend for lower risk. Conclusion In tofacitinib users, HZ occurred at a rate of approximately 4% per year and was further doubled with glucocorticoid exposure. Concomitant MTX did not confer additional risk. Zoster vaccination may decrease risk.