Immune Response After Human Papillomavirus Vaccination in Patients With Autoimmune Disease
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
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
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.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Diagnostic
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.
0, 3, 7, 12 months
Nico M Wulffraat, MD, PhD
Netherlands: Ministry of Health, Welfare and Sport