Effect of Two-week Discontinuation of Methotrexate on Efficacy of Seasonal Influenza Vaccination in Patients With Rheumatoid Arthritis: A Randomized Clinical Trial
试验速览
- 阶段
- 不适用
- 入组人数
- 318
- 试验地点
- 3
- 主要终点
- Proportion of satisfactory vaccine response
研究概览
简要总结
To investigate whether a transient discontinuation of methotrexate MTX for 2 weeks improves the vaccination response to a seasonal influenza.
详细描述
Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease that affects the joints as the main target of the inflammation. Patients with RA require chronic treatment with disease modifying antirheumatic drugs (DMARDs) including methotrexate (MTX), which constitutes the mainstay of treatment. Underlying immune dysfunction and the additional immune suppression associated with treatment render patients with RA more susceptible to infection. Thus, vaccination of the preventive diseases is crucial and recommended in all patients unless contraindicated.
However, low dose of glucocorticoids, conventional DMARDs and biological DMARDs including tumor necrosis factor inhibitors have been reported to substantially decrease vaccine response (4); MTX has been reported to be associated with a decreased response to seasonal influenza vaccination by up to 15%.
To optimize a vaccine response, vaccination should be administrated before the treatment with immunesuppressive medications is initiated. However, most patients with RA are already on stable dose of MTX at the time of when vaccinations. To improve the vaccine response, a short term discontinuation of MTX could be considered. In a prior study, we discovered that a temporary discontinuation of MTX for 4 weeks during peri-vaccination period tended to be associated with an improved response to vaccination with trivalent influenza vaccination (Figure 1). It remains to be defined whether MTX discontinuation for shorter period increases the vaccination efficacy while minimizing the RA flare rate.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males or females ≥ 19 years and < 65 years of age at time of consent
- •Have a diagnosis of RA per ACR criteria
- •Must understand and voluntarily sign an informed consent form including writing consent for data protection
- •Stable doses of methotrexate over the preceding 6 weeks
排除标准
- •Pregnant or lactating females
- •Previous anaphylactic response to vaccine components or to egg.
- •Acute infection with T >38°C at the time of vaccination
- •History of Guillain-Barre syndrome or demyelinating syndromes
- •Previous vaccination with any live vaccine 4 weeks before or any inactivated vaccine 2 weeks before the study
- •Blood transfusion within 6 months
- •Active rheumatoid arthritis necessitating a recent change in the drug regimen
- •Any other rheumatic disease such as systemic lupus erythematosus, mixed connective tissue disease, dermatomyositis/polymyositis, and vasculitis except for secondary Sjogren's disease
- •Any condition including laboratory abnormality which places the subject at unacceptable risk
- •Subjects who decline to participate
研究组 & 干预措施
Group 1: MTX continue
Group will continue MTX after vaccination
干预措施: Methotrexate (Drug)
Group 2: MTX hold
will hold MTX for 2 weeks after vaccination
干预措施: Methotrexate (Drug)
结局指标
主要结局
Proportion of satisfactory vaccine response
时间窗: 4 weeks
Proportion of satisfactory vaccine response that is defined as ≥ 4-fold increase in post-vaccination titer in ≥ 2 of 4 influenza strains
次要结局
- Proportion of patients who have ≥ 4-fold increase in post-vaccination titer in ≥ 3 of 4 influenza strains(4 weeks)
- Proportion of seroprotection for each strain(4 weeks)
- Change from baseline in titer (in GMT) for each strain(4 weeks)
- Change from baseline in DAS28-4 (CRP) at 4 weeks after vaccination(4 weeks)
- Proportion of patients who experience increase in disease activity(4 weeks)
研究者
Eun Bong Lee
Professor
Seoul National University Hospital