Immune Response After Human Papillomavirus Vaccination in Patients With Autoimmune Disease
Condition: Juvenile Idiopathic Arthritis; Systemic Lupus Erythematosus; Juvenile Dermatomyositis
MeSH terms: Arthritis, Juvenile; Dermatomyositis; Lupus Erythematosus, Systemic; Autoimmune Diseases
Study type: Interventional
Phase: Phase 4

Summary: 
      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.
    

Detailed description: 
      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.

      Nature and extent of the burden and risks associated with participation, benefit and group
      relatedness:

      Burden: included patients will be asked to visit the hospital 4 times in a period of 12
      months. During these visits, physical examination will be performed and blood will be
      obtained for serological and immunological analysis. Most of these visits are combined with
      routine follow-up and venous punctures of the patients. However, one extra visit to the
      hospital and vena puncture is expected. 5 ml (extra) blood is obtained four times from all
      patients for serological analysis. Included healthy controls will be asked to visit one
      plenary information meeting in the evening. Controls will have a venous punctures four times
      during the study, during which 5 ml of blood is obtained. These samples will be obtained at
      the hospital during evening clinics or at school. In a subset of patients (n=50) and healthy
      controls (n=10), an additional 15 ml is obtained for immunological analysis.

      Risks: participants may experience adverse events of the HPV vaccination. Benefits:
      Protection against human Papillomavirus infection and therefore reduced risk of cervix
      carcinoma, certainty about protection against HPV 16 & 18 and about safety of HPV
      vaccination.

      Group relatedness: This study can only be done in patients who need this vaccination (i.e.
      females in the age group 12-24 years) and have an immune system disorder, such as JIA, SLE or
      JDM. Appropriate comparison with healthy controls must be performed in age-matched healthy
      females who are also recruited for the National HPV vaccination campaign, in this case girls
      in the age group 13-17 years.
    

Intervention name(s): Human papilloma virus vaccine (cervarix)
Intervention type(s): Other
Intervention description(s): vaccination at 0, 1 and 6 months
Other intervention name(s): Cervarix vaccine (GlaxoSmithKLine)
Intervention MeSH terms: Vaccines
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic