2-week dc of MTX and Influenza Vaccination in RA

Study Overview
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Brief Summary
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To investigate whether a transient discontinuation of methotrexate MTX for 2 weeks improves the vaccination response to a seasonal influenza.

Detailed Description
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Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease that affects the joints as the main target of the inflammation. Patients with RA require chronic treatment with disease modifying antirheumatic drugs (DMARDs) including methotrexate (MTX), which constitutes the mainstay of treatment. Underlying immune dysfunction and the additional immune suppression associated with treatment render patients with RA more susceptible to infection. Thus, vaccination of the preventive diseases is crucial and recommended in all patients unless contraindicated. However, low dose of glucocorticoids, conventional DMARDs and biological DMARDs including tumor necrosis factor inhibitors have been reported to substantially decrease vaccine response (4); MTX has been reported to be associated with a decreased response to seasonal influenza vaccination by up to 15%. To optimize a vaccine response, vaccination should be administrated before the treatment with immunesuppressive medications is initiated. However, most patients with RA are already on stable dose of MTX at the time of when vaccinations. To improve the vaccine response, a short term discontinuation of MTX could be considered. In a prior study, we discovered that a temporary discontinuation of MTX for 4 weeks during peri-vaccination period tended to be associated with an improved response to vaccination with trivalent influenza vaccination (Figure 1). It remains to be defined whether MTX discontinuation for shorter period increases the vaccination efficacy while minimizing the RA flare rate.

Official Title
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Effect of Two-week Discontinuation of Methotrexate on Efficacy of Seasonal Influenza Vaccination in Patients With Rheumatoid Arthritis: A Randomized Clinical Trial

Conditions
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Rheumatoid Arthritis, Influenza, Methotrexate

Intervention / Treatment
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* Drug: Methotrexate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females ≥ 19 years and < 65 years of age at time of consent Have a diagnosis of RA per ACR criteria Must understand and voluntarily sign an informed consent form including writing consent for data protection Stable doses of methotrexate over the preceding 6 weeks Exclusion Criteria: Pregnant or lactating females Previous anaphylactic response to vaccine components or to egg. Acute infection with T >38°C at the time of vaccination History of Guillain-Barre syndrome or demyelinating syndromes Previous vaccination with any live vaccine 4 weeks before or any inactivated vaccine 2 weeks before the study Blood transfusion within 6 months Active rheumatoid arthritis necessitating a recent change in the drug regimen Any other rheumatic disease such as systemic lupus erythematosus, mixed connective tissue disease, dermatomyositis/polymyositis, and vasculitis except for secondary Sjogren's disease Any condition including laboratory abnormality which places the subject at unacceptable risk Subjects who decline to participate

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: Group 1: MTX continue<br>Group will continue MTX after vaccination | Drug: Methotrexate<br> <br> |
| Experimental: Group 2: MTX hold<br>will hold MTX for 2 weeks after vaccination | Drug: Methotrexate<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of satisfactory vaccine response | Proportion of satisfactory vaccine response that is defined as ≥ 4-fold increase in post-vaccination titer in ≥ 2 of 4 influenza strains | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients who have ≥ 4-fold increase in post-vaccination titer in ≥ 3 of 4 influenza strains |  | 4 weeks | 
| Proportion of seroprotection for each strain |  | 4 weeks | 
| Change from baseline in titer (in GMT) for each strain |  | 4 weeks | 
| Change from baseline in DAS28-4 (CRP) at 4 weeks after vaccination |  | 4 weeks | 
| Proportion of patients who experience increase in disease activity |  | 4 weeks |