Yellow Fever Vaccination Under Low Dose Methotrexate Therapy

Study Overview
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Brief Summary
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Travelers (n = 30, 15 taking low-dose methotrexate (MTX), 15 healthy controls (HC), seeking travel advice in one of the following Swiss Travel Centers (Aarau, Basel, Bern, Geneva, Lausanne, Zurich) and who have an indication for yellow fever (YF) vaccination according to the Swiss Federal Office of Public Health's vaccination recommendations are invited to participate in this study. After signing the consent form (i) YF viremia and (ii) anti-YF antibody production in patients taking low-dose MTX and HC will be compared after YF vaccination. It will be analyzed whether the percentage of people with protective antibodies differs between the two groups and (iii) vaccine side effects will be compared between the groups.

Detailed Description
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The study will be conducted in the form of a multi-center open-label prospective observational controlled pilot study. 15 patients under low dose methotrexate treatment and 15 healthy controls with an indication for yellow fever vaccination will be included. The study duration will be 28 days for each subject and will consist of 6 clinical visits on days 0, 3, 7, 10, 14 and 28. YF antibodies will be measured on days 0, 7, 10, 14 and 28; viremia will be measured on days 3, 7, 10, 14 and 28.

Official Title
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Yellow Fever Vaccination Under Low Dose Methotrexate Therapy - a Multi-Center Prospective Observational Controlled Pilot Study

Conditions
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Rheumatic, Dermatologic Disorders

Intervention / Treatment
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* Biological: Yellow Fever Vaccination


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed Consent as documented by signature Indication for yellow fever vaccination according to Swiss FOPH recommendations Individuals under low dose MTX (≤20mg/week) therapy or healthy individuals Male and Female travelers ≥18 years to <60 years of age Exclusion Criteria: Contraindications on ethical grounds Women who are pregnant or breast feeding Contraindication against yellow fever vaccination (e.g. hypersensitivity against vaccine ingredient) Current treatment with other immunosuppressive agent apart from low dose methotrexate Alemtuzumab or rituximab in the last year TNF-blocking therapy in past three months Immunocompromising condition in healthy control Other immunocompromising condition than MTX treatment itself and the underlying disease in patients under MTX Previous yellow fever vaccination No indication for yellow fever vaccination according to Swiss travel vaccination recommendations Known or suspected non-compliance, drug or alcohol abuse Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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 |
| --- | --- |
| Patients under low dose methotrexate therapy<br>Patients with various underlying conditions (e.g. rheumatic diseases, dermatologic diseases) who have an indication for yellow fever vaccination | Biological: Yellow Fever Vaccination<br>* The Yellow Fever vaccination is actually not part of the study. Only individuals who have an indication for yellow fever vaccination according to Swiss vaccination recommendations will be enrolled. Study procedures will include blood collection to measure antibody development and viremia as well as data collection on possible side effects.<br>|
| Healthy controls<br>Healthy travelers who have an indication for yellow fever vaccination | Biological: Yellow Fever Vaccination<br>* The Yellow Fever vaccination is actually not part of the study. Only individuals who have an indication for yellow fever vaccination according to Swiss vaccination recommendations will be enrolled. Study procedures will include blood collection to measure antibody development and viremia as well as data collection on possible side effects.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quantitative viremia in blood in travelers under low dose methotrexate (≤20mg/week) and healthy travelers | Serum samples will be collected for PCR | days 3, 7, 10 and 14 and 28 | 
| Quantitative yellow fever specific neutralizing antibodies in blood of travelers under low dose methotrexate therapy (≤20mg/week) and healthy travelers | Serum samples will be collected for measurement of neutralizing antibodies | days 0, 7, 10, 14 and 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determination of the percentage of travelers with an antibody level of >0.7 LNI (>0.5 IU/ml) in both groups |  | days 0, 7, 10, 14, 28 | 
| Assessment of safety by determining the severity and quantity of adverse vaccine reactions such as local and systemic reactions in both study groups | Local and systemic vaccine reactions will be collected in a diray card filled out by the participant | Throughout day 28 after vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Methotrexate therapy