Immune Response After Human Papillomavirus Vaccination in Patients With Autoimmune Disease
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 135
- 试验地点
- 3
- 主要终点
- the immunogenicity of HPV vaccination in patients with immune system disorders. The immunogenicity of HPV vaccination in patients will be compared to healthy controls, measured by antibody levels against HPV serotype 16 & 18.
研究概览
简要总结
In the Netherlands, the human Papillomavirus (HPV) vaccination will be added to the National Vaccination Program for girls to protect against the development of cervical cancer. The vaccine protects against HPV type 16 & 18, which cause about 75% of cervical cancer. Studies have shown that the vaccine is effective in healthy subjects in preventing infection by HPV 16 & 18. However, no evidence exists on the immunogenicity and safety of HPV vaccination in patients with an immune system disorder, such as primary humoral immunodeficiency (i.e. hypogammaglobulinemia) or autoimmune diseases. Concerns exist that vaccination may cause an aggravation of the underlying disease. In addition, the immune response to vaccination may be diminished due to immunosuppressive therapy or the underlying disease.
Objective: The primary goal of the current study is to study the immunogenicity of HPV vaccination in patients with an autoimmune disease and a primary humoral immunodeficiency.
Based on retrospective analysis with other vaccines we hypothesize that patients with autoimmune diseases who are under immunosuppressive medication and patients with a immune system disorder have a decreased serological response to HPV vaccination, and that the produced HPV antibodies titers decrease more rapidly than in healthy individuals.
The secondary objective is to explore safety of HPV vaccination and immune regulatory mechanisms induced by vaccination in a subset of patients. The investigators hypothesize that HPV vaccination is safe and that HPV-induced regulatory T cells are able to prevent an increase in the activity of an autoimmune disease.
详细描述
Study design: prospective observational cohort study.
Study population: Females aged 12 - 18 years with one of the autoimmune diseases Juvenile Idiopathic Arthritis (JIA), Systemic Lupus Erythematosus (SLE) and Juvenile Dermatomyositis (JDM) are included. Included females are treated at the rheumatology unit from the University Medical Center Utrecht. A small control group of healthy girls aged 13 -17 years will also be included to compare the kinetics of HPV serology with healthy individuals.
Intervention: Starting from September 2009 all girls aged 12 years will be offered a HPV vaccination via the National Vaccination Program. Prior to this, a national campaign will be started in March 2009 to vaccinate all girls aged 13-17 years at once.We will use this national vaccination campaign as an opportunity to analyze the serological response and safety of this vaccine in a large group of with an immune system disorder. The vaccines are administered by our national health organisation. The effects are monitored in our clinics.
Main study parameters/endpoints:
- Primary outcome immunogenicity is measured by antibody levels against HPV serotype 16 & 18 over time. We consider HPV vaccination to be immunogenic at antibody titers above the cutoffs 20 and 24 mMU/ml for HPV 16 and 18, respectively; or at a ≥2 fold increase in antibody levels against both serotypes. The antibody levels will be measured prior to vaccination, and after 3,7 and 12 months.
- The secondary outcome is safety of vaccination, measured as activity of the underlying autoimmune disease. In addition, frequency of common adverse effects, and immunological changes induced by HPV vaccination, such as number and function of cytotoxic T cells and Tregs will be described.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 18 Years（Child, Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Clinical diagnosis of JIA, SLE or JDM
- •And who are in the following age groups:
- •12 years (these girls are vaccinated via the National Vaccination Program from September 2009)
- •13-18 years (these girls are vaccinated during a national vaccination campaign from March-May 2009)
- •Current co-medication: all co-medication prescribed may be continued
- •And in the control group: healthy girls aged 13-17 years (these girls are vaccinated during a national vaccination campaign from March-May 2009)
排除标准
- •No HPV vaccination
- •Refusal to allow venous puncture
- •Proven or suspected cervical carcinoma
研究组 & 干预措施
Patients
patients were girls aged 15 to 18 immunised with the HPV vaccine according to dutch vaccination guidelines
干预措施: Human papilloma virus vaccine (cervarix) (Other)
结局指标
主要结局
the immunogenicity of HPV vaccination in patients with immune system disorders. The immunogenicity of HPV vaccination in patients will be compared to healthy controls, measured by antibody levels against HPV serotype 16 & 18.
时间窗: 0, 3, 7, 12 months
次要结局
- difference in the activity of underlying disease before versus after vaccination. A difference in the activity of underlying autoimmune disease, will be measured according to specific criteria for each autoimmune disease.(0,3,7,12 months)
研究者
N.M. Wulffraat
MD
UMC Utrecht