Cleveland Clinic Foundation, Cleveland, Ohio.
Hospital Central, San Luis Potosí, Mexico.
Arthritis Care Res (Hoboken). 2020 Mar;72(3):353-359. doi: 10.1002/acr.24010.
To explore herpes zoster (HZ) rates and live zoster vaccine (LZV) safety in a subset of patients with rheumatoid arthritis who received LZV before tofacitinib ± methotrexate (MTX), or adalimumab (ADA) plus MTX in the ORAL Strategy.
ORAL Strategy was a 1-year, phase IIIb/IV, randomized, triple-dummy, active-comparator-controlled study. MTX-inadequate responder patients received tofacitinib 5 mg twice daily (BID), tofacitinib 5 mg BID plus MTX, or ADA 40 mg every other week plus MTX (1:1:1 randomization). Eligible patients age ≥50 years could opt to receive LZV 28 days before initiating study treatment. HZ incidence rates (IRs; patients with events per 100 patient-years) were calculated. Opportunistic HZ infections (multidermatomal/disseminated), serious HZ events, and LZV-related adverse events were monitored.
In ORAL Strategy, 216 of 1,146 patients (18.8%) received LZV. Overall, 18 patients (1.6%) developed HZ (vaccinated: n = 3; nonvaccinated: n = 15). HZ IRs were 1.1 (95% confidence interval [95% CI] 0.3-2.9), 2.3 (95% CI 1.0-4.6), and 1.7 (95% CI 0.6-3.7) for tofacitinib monotherapy, tofacitinib plus MTX, and ADA plus MTX, respectively, and were generally similar between vaccinated and nonvaccinated patients. Three multidermatomal, 1 disseminated, and 2 serious HZ events occurred. No vaccinated patients had zoster-like lesions within 42 days of vaccination; 1 patient had vaccination-site erythema.
LZV was well tolerated, and HZ IRs were generally similar between treatment groups and vaccinated versus nonvaccinated patients. However, ORAL Strategy was not powered for comparisons between vaccinated and nonvaccinated patients because <20% of all patients were vaccinated. Furthermore, LZV has been shown to be effective only in ~50% of individuals.
在接受托法替布±甲氨蝶呤（MTX）或阿达木单抗（ADA）+ MTX 的类风湿关节炎患者亚组中，探索带状疱疹（HZ）发生率和带状疱疹活疫苗（LZV）安全性。
ORAL 策略是一项为期 1 年、IIIb/IV 期、随机、三盲、活性对照研究。MTX 应答不足的患者接受托法替布 5mg 每日 2 次（BID）、托法替布 5mg BID+MTX 或 ADA 40mg 每 2 周 1 次+MTX（1:1:1 随机分组）。年龄≥50 岁且符合条件的患者可选择在开始研究治疗前 28 天内接种 LZV。HZ 发生率（IR；每 100 患者-年出现事件的患者数）进行计算。监测偶发性 HZ 感染（多节段/播散性）、严重 HZ 事件和与 LZV 相关的不良事件。
在 ORAL 策略中，1146 例患者中有 216 例（18.8%）接种了 LZV。总体而言，18 例（1.6%）发生 HZ（接种组：n=3；未接种组：n=15）。HZ IR 分别为托法替布单药治疗、托法替布+MTX 和 ADA+MTX 的 1.1（95%置信区间[95%CI]0.3-2.9）、2.3（95%CI 1.0-4.6）和 1.7（95%CI 0.6-3.7），接种组和未接种组患者之间的差异无统计学意义。发生 3 例多节段、1 例播散性和 2 例严重 HZ 事件。无接种患者在接种后 42 天内出现带状疱疹样病变；1 例患者接种部位出现红斑。
LZV 耐受性良好，且治疗组和接种组与未接种组之间的 HZ IR 差异无统计学意义。然而，由于接种患者不到所有患者的 20%，因此 ORAL 策略没有对接种组和未接种组患者进行比较的效力。此外，LZV 的有效性仅在约 50%的个体中得到证实。
