Immunogenicity and Safety of Vaccinations in Immunocompromised Persons

Study Overview
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Brief Summary
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Backgound and relevance of the project: Patients with autoimmune inflammatory rheumatic diseases (AIIRD) are at increased risk of contracting infections. The increased risk can be attributed to the immunological disorder itself, as well as to the immunosuppressive treatment. Vaccination against many infections is recommended in this patient group. However, the immunogenicity of vaccines may be reduced and may also be influenced by the administered treatment. Potential reactivation of the underlying disease triggered by vaccination is another important concern. From the patients' and public health perspectives, an important task of physicians is giving advice on vaccines. Completing this task is often difficult, because data on the immunogenicity and safety of vaccines in these patient groups are scarce, especially with regard to treatment with new immunosuppressive medications, such as biological agents. Lastly and importantly, due to new therapeutic options, health among AIIRD patients has considerably improved and an increasing number of patients undertake overseas travel activities requiring additional vaccinations. In this context, reliable advice with regard to vaccinations is almost impossible, because for most travel vaccinations the immunogenicity and safety profile is unknown. Research addressing the immunogenicity and safety of vaccines in different autoimmune inflammatory diseases treated with different immunosuppressive medications is urgently needed to allow giving evidence based vaccine advice. In this observational study the immunogenicity and safety of tetanus booster and hepatitis A vaccinations will be assessed in AIIRD patients. The immune response will be evaluated as a function of the underlying disease and the possible influence of commonly used immunosuppressive drugs on the immune response will be studied. Rationale for studying tetanus booster and hepatitis A vaccine Tetanus vaccination is one of the most frequently recommended vaccinations, and the effect of a booster vaccination can be addressed. Hepatitis A vaccine is the most widely used travel vaccine. Despite their importance, only very limited data are available for tetanus and hepatitis A vaccine in this patient group. By focusing on these vaccines the study will lead the way to the evaluation of further vaccines. The purpose of this study is to determine whether tetanus and hepatitis A vaccinations are as immunogenic and safe in AIIRD patients as in healthy controls.

Detailed Description
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The study will be placed in 6 rheumatology clinics in Switzerland and in 4 travel medicine clinics. Consecutive subjects with rheumatoid arthritis, spondylarthritis (ankylosing spondylitis), vasculitis (ANCA associated vasculitis and Behçet's disease) and healthy controls will be recruited.

Official Title
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A Prospective Cohort Study in 6 Swiss Rheumatology Centres and 4 Travel Clinics on the Immunogenicity and Safety of Tetanus and Hepatitis A Vaccine in Patients With Rheumatoid Arthritis, Axial Spondyloarthritis and Vasculitis and Healthy Controls

Conditions
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Arthritis, Rheumatoid, Spondylarthritis, Vasculitis

Intervention / Treatment
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* Biological: Hepatitis A vaccine and tetanus vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Indication for hepatitis A and/or tetanus vaccination according to Swiss Federal Office of Public Health recommendations Male and female rheumatic patients with rheumatoid arthritis or axial spondyloarthritis (ankylosing spondylitis, axial psoriatic arthritis, axial undifferentiated spondyloarthritis, enteropahtic arthritis) or peripheral psoriatic arthritis or vasculitis (Behçet's disease or ANCA-associated vasculitis) or male and female healthy participants ≥ 18 years Signed Informed Consent after being informed Exclusion Criteria: Known hypersensitivity to a vaccine ingredient Estimated patient survival below 1 year Active malignant or active infectious disease Drug/alcohol abuse Insufficient understanding of local language

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Healthy controls<br>If a vaccination is indicated according to the recommendations by the Swiss Federal Office of Public Health: 319 healthy controls will be enrolled and will receive hepatitis A and/or tetanus vaccination | Biological: Hepatitis A vaccine and tetanus vaccine<br>* Hepatitis A and/or tetanus vaccination will be given to participants in all group on day 0. All monovalent active hepatitis A vaccinations and all vaccines containing tetanus toxoid available in Switzerland may be used in the study<br>* Other names: Revaxis;|
| Patients with rheumatoid arthritis<br>If a vaccination is indicated according to the recommendations by the Swiss Federal Office of Public Health: 142 patients with rheumatoid arthritis will be enrolled and will receive hepatitis A and/or tetanus vaccination. | Biological: Hepatitis A vaccine and tetanus vaccine<br>* Hepatitis A and/or tetanus vaccination will be given to participants in all group on day 0. All monovalent active hepatitis A vaccinations and all vaccines containing tetanus toxoid available in Switzerland may be used in the study<br>* Other names: Revaxis;|
| Patients with axial spondylarthritis<br>If a vaccination is indicated according to the recommendations by the Swiss Federal Office of Public Health: 142 patients with axial spondylarthritis will be enrolled and will receive hepatitis A and/or tetanus vaccination. | Biological: Hepatitis A vaccine and tetanus vaccine<br>* Hepatitis A and/or tetanus vaccination will be given to participants in all group on day 0. All monovalent active hepatitis A vaccinations and all vaccines containing tetanus toxoid available in Switzerland may be used in the study<br>* Other names: Revaxis;|
| Patients with vasculitis<br>If a vaccination is indicated according to the recommendations by the Swiss Federal Office of Public Health: 142 patients with vasculitis will be enrolled and will receive hepatitis A and/or tetanus vaccination. | Biological: Hepatitis A vaccine and tetanus vaccine<br>* Hepatitis A and/or tetanus vaccination will be given to participants in all group on day 0. All monovalent active hepatitis A vaccinations and all vaccines containing tetanus toxoid available in Switzerland may be used in the study<br>* Other names: Revaxis;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunogenicity of hepatitis A and tetanus vaccination in patients with rheumatoid arthritis, axial spondyloarthritis and vasculitis and in healthy controls | comparison of the geometric mean antibody titre and percentage of seroprotected individuals after tetanus and hepatitis A vaccination between each disease group and healthy controls | Change from Baseline in geometric mean antibody titre and seroprotection at 4 weeks and at 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of tetanus and hepatitis A vaccines in patients with rheumatoid arthritis, axial spondyloarthritis and vasculitis and in healthy controls | Number of patients with any worsening or reactivation of the rheumatic disease after vaccine administration Number of participants with adverse vaccine reactions (local and systemic reactions) in patients with rheumatoid arthritis, axial spondyloarthritis and vasculitis and in healthy controls | Activation of rheumatic disease will be assessed for 1 week after vaccine administration and at 4 and 12 weeks compared to baseline |