病毒活疫苗的安全性和有效性,比如水痘-带状疱疹疫苗,在接受免疫调节治疗如肿瘤坏死因子抑制剂(TNF-α)的炎症性疾病患者中未知。
评价在接受TNF-α治疗的患者中,减毒带状疱疹活疫苗(ZVL)的安全性和免疫原性。
随机化,失明,安慰剂对照试验。(ClinicalTrials.gov:NCT02538341)。
学术和社区风湿病学,胃肠病学,和皮肤病学实践。
50岁或以上的成年人接受TNFis的任何适应症。
随机分配给ZVL与安慰剂。
在基线和接种后6周测量血清和外周血单核细胞的糖蛋白酶联免疫吸附测定(gpELISA)和酶联免疫吸附斑点(ELISpot)。使用数码照片和囊状液的聚合酶链反应对疑似水痘感染或带状疱疹进行临床评估。在2015年3月至2018年12月之间,617名参与者以1:1的比例随机分配,在33个中心接受ZVL(n=310)或安慰剂(n=307)。平均年龄为62.7岁(SD,7.5);66.1%的参与者是女性,90%是白人,8.2%是黑人,5.9%是西班牙裔。最常见的TNFi适应症是类风湿性关节炎(57.6%)和银屑病关节炎(24.1%);TNFi药物是阿达木单抗(32.7%),英夫利昔单抗(31.3%),依那西普(21.2%),戈利木单抗(9.1%),和赛托珠单抗(5.7%)。合并治疗包括甲氨蝶呤(48.0%)和口服糖皮质激素(10.5%)。至第6周,未发现水痘感染的确诊病例;水痘感染或带状疱疹的累积发生率为0.0%(95%CI,0.0%至1.2%)。在6周,与基线相比,通过gpELISA和ELISpot测量的几何平均倍数上升的平均增加为1.33个百分点(CI,1.17至1.51个百分点)和1.39个百分点(CI,1.07至1.82个百分点),分别。
对接受其他类型免疫调节剂的患者的普适性可能有限。
本试验告知在接受生物制剂的患者中使用活病毒疫苗相关的安全问题。
国家关节炎和肌肉骨骼和皮肤病研究所和美国风湿病学会。
The safety and effectiveness of live virus vaccines, such as the varicella-zoster vaccine, are unknown in patients with inflammatory diseases receiving immunomodulatory therapy such as tumor necrosis factor inhibitors (TNFis).
To evaluate the safety and immunogenicity of the live attenuated zoster vaccine (ZVL) in patients receiving TNFis.
Randomized, blinded, placebo-controlled
trial. (ClinicalTrials.gov: NCT02538341).
Academic and community-based rheumatology, gastroenterology, and dermatology practices.
Adults aged 50 years or older receiving TNFis for any indication.
Random assignment to ZVL versus placebo.
Glycoprotein enzyme-linked immunosorbent assay (gpELISA) and enzyme-linked immunosorbent spot (ELISpot) from serum and peripheral blood mononuclear cells measured at baseline and 6 weeks after vaccination. Suspected varicella infection or herpes zoster was clinically assessed using digital photographs and polymerase chain reaction on vesicular fluid.
Between March 2015 and December 2018, 617 participants were randomly assigned in a 1:1 ratio to receive ZVL (n = 310) or placebo (n = 307) at 33 centers. Mean age was 62.7 years (SD, 7.5); 66.1% of participants were female, 90% were White, 8.2% were Black, and 5.9% were Hispanic. The most common TNFi indications were rheumatoid arthritis (57.6%) and psoriatic arthritis (24.1%); TNFi medications were adalimumab (32.7%), infliximab (31.3%), etanercept (21.2%), golimumab (9.1%), and certolizumab (5.7%). Concomitant therapies included methotrexate (48.0%) and oral glucocorticoids (10.5%). Through week 6, no cases of confirmed varicella infection were found; cumulative incidence of varicella infection or shingles was 0.0% (95% CI, 0.0% to 1.2%). At 6 weeks, compared with baseline, the mean increases in geometric mean fold rise as measured by gpELISA and ELISpot were 1.33 percentage points (CI, 1.17 to 1.51 percentage points) and 1.39 percentage points (CI, 1.07 to 1.82 percentage points), respectively.
Potentially limited generalizability to patients receiving other types of immunomodulators.
This
trial informs safety concerns related to use of live virus vaccines in patients receiving biologics.
The National Institute of Arthritis and Musculoskeletal and Skin Diseases and the American College of Rheumatology.