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2-week dc of MTX and Influenza Vaccination in RA

Not Applicable
Conditions
Rheumatoid Arthritis
Influenza
Methotrexate
Interventions
Registration Number
NCT02897011
Lead Sponsor
Seoul National University Hospital
Brief Summary

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

Detailed Description

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.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
318
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Group 1: MTX continueMethotrexateGroup will continue MTX after vaccination
Group 2: MTX holdMethotrexatewill hold MTX for 2 weeks after vaccination
Primary Outcome Measures
NameTimeMethod
Proportion of satisfactory vaccine response4 weeks

Proportion of satisfactory vaccine response that is defined as ≥ 4-fold increase in post-vaccination titer in ≥ 2 of 4 influenza strains

Secondary Outcome Measures
NameTimeMethod
Proportion of patients who have ≥ 4-fold increase in post-vaccination titer in ≥ 3 of 4 influenza strains4 weeks
Proportion of seroprotection for each strain4 weeks
Change from baseline in titer (in GMT) for each strain4 weeks
Change from baseline in DAS28-4 (CRP) at 4 weeks after vaccination4 weeks
Proportion of patients who experience increase in disease activity4 weeks

Trial Locations

Locations (3)

SMG-SNU Boramae Medical Center

🇰🇷

Seoul, Korea, Republic of

Seoul National Univ. Bundang Hospital

🇰🇷

Bundang, Gyeonggi-do, Korea, Republic of

Seoul National University Hospital

🇰🇷

Seoul, Korea, Republic of

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