Three Doses of Hepatitis A Vaccine in Patients With Immunomodulating Drugs

Study Overview
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Brief Summary
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Hepatitis A vaccine is the most frequently used traveler's vaccine, yet data on its ability to induce protective immunity in immunosuppressed travelers are scarce. The investigators assess the hepatitis A virus (HAV) antibody response in patients with rheumatoid arthritis (RA) treated with Tumor Necrosis Factor (TNF) - inhibitors and/or methotrexate (Mtx). In a previous study, 2 doses were not considered effective and there is therefore need for a study with an additional dose

Detailed Description
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Methods: Parameters registered at baseline were: age, sex, duration of disease, medications, activity of disease (Visual Analogue Scale), Health Assessment Questionnaire Disability Index, Disease Activity Score, Acute phase reactant and total immunoglobulin G in plasma). Hepatitis A vaccine (Epaxal or Havrix) were given at 0 and 6 months. Hepatitis A virus (HAV) antibodies is measured before vaccination and at month 1, 6 (before dose 2), 7 and 12 with quantitative HAV IgG, using the HAVAb-IgG Architect System, and by the HAVAB 2.0 assay on the AxSYM machine from Abbott. The level of protective immunity to HAV is defined as HAV IgG > 10mIU/mL.

Official Title
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Hepatitis A Vaccination in Patients With Rheumatoid Arthritis Treated With TNF-inhibitors and/or Methotrexate

Conditions
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Vaccine Response Impaired

Intervention / Treatment
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* Biological: hepatitis A vaccine
* Biological: hepatitis A vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of rheumatoid arthritis TNF-alfa blocker and / or methotrexate in use as a medication against RA A desire to get protected against hepatitis A Men and women age 18-65 years Written informed consent Women of childbearing potential must use effective contraception - Exclusion Criteria: Treatment with rituximab within 9 months before study start Known previous hepatitis A infection Previous vaccination against hepatitis A Allergy to eggs or formaldehyde Pregnancy or lactation Excessive use of alcohol Mental retardation Acute disease at the time of examination (fever > 38 degrees) Volunteer works as an employee of the researchers Previous vaccination against hepatitis A Egg-, hen-protein- or formaldehyde allergy Pregnancy or lactation Excessive use of alcohol Another vaccine given within a month Acute disease at the time of examination (fever > 38 degrees) Not suitable for other reason in the investigator's opinion (other serious disease, i.e. AIDS/HIV-positive, cancer with ongoing cytostatic treatment)

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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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: initial single dose of hep A vaccine<br>The participants will receive a single dose of hepatitis A vaccine at 0+1+6 months | Biological: hepatitis A vaccine<br>* 3 doses of hepatitis A vaccine, given at 0+1+6 months<br>|
| Active Comparator: initial double dose<br>Participants will receive one dose of hepatitis A vaccine in each M. deltoids and an additional dose at 6 months later | Biological: hepatitis A vaccine<br>* Two doses of hepatitis A vaccine given at day 0, one in each M deltoids. An additional dose will be given at 6 months later<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| seroconversion after the first dose/doses of hepatitis A vaccine | ELISA-titers are determined before the first dose/doses and at 1 month later | one month after the first dose/doses | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| seroconversion rates after three doses of hepatitis A vaccine | We determine seroconversion rates before the third vaccine dose (6 months after the first) and at 1 and 6 months after the second dose | 12 months after the first doses | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hepatitis A vaccine, TNF-alfa inhibitory drugs, Rheumatoid arthritis, methotrexate