MTX Discontinuation and Vaccine Response

November 29, 2017 updated by: Eun Bong Lee, Seoul National University Hospital

Effect of Methotrexate Discontinuation on Efficacy of Seasonal Influenza Vaccination in Patients With Rheumatoid Arthritis: A Randomized Clinical Trial

To investigate whether a short term discontinuation of methotrexate (MTX) will improve the vaccination efficacy to seasonal influenza vaccination without deteriorating RA disease activity in a randomized clinical trial.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 anti-rheumatic 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 against preventable diseases including influenza, pneumococcal pneumonia and hepatitis B is recommended for all RA patients who are subject to treatment with immunesupprssive drugs, unless there is a contraindication to the use of vaccination. 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 DMARDs at the time of when vaccinations, especially vaccine against seasonal influenza that needs annual administration, are considered. Alternatively, temporarily discontinuation of DMARDs might restore normal immune response to and so improve the efficacy of vaccination.

Although a short term discontinuation of DMARDs during perioperative period has not been associated with increased disease activity the longer discontinuation of DMARDs might lead to a significant aggravation of RA disease activity. To optimize the vaccine response, a short term discontinuation of DMARDs could be considered if this approach proves to be safe and effective.

Study Type

Interventional

Enrollment (Actual)

277

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Korea, Republic of
      • Seoul, Korea, Republic of, 110-744
        • Seoul National University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Males or females > 18 years 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Group 1 (No MTX Hold before Vaccination)
Group 1 will continue MTX
Drug: Methotrexate
Methotrexate will be continued
Biological: Seasonal Influenza vaccine
all subjects will be vaccinated with a seasonal influenza vaccine
Experimental: Group 2 (MTX hold 4 Weeks before vaccination)
Group 2 will hold MTX 4 weeks before vaccination and resume MTX on the day of vaccination
Drug: Methotrexate
Methotrexate will be continued
Biological: Seasonal Influenza vaccine
all subjects will be vaccinated with a seasonal influenza vaccine
Experimental: Group 3 (MTX hold 2 Weeks before Vaccination)
Group 3 will hold MTX 2 weeks before vaccination and resume MTX 2 weeks after vaccination
Drug: Methotrexate
Methotrexate will be continued
Biological: Seasonal Influenza vaccine
all subjects will be vaccinated with a seasonal influenza vaccine
Experimental: Group 4 (MTX hold on Day of Vaccination)
Group 4 will hold MTX on day of vaccination and resume MTX 4 weeks after vaccination.
Drug: Methotrexate
Methotrexate will be continued
Biological: Seasonal Influenza vaccine
all subjects will be vaccinated with a seasonal influenza vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Satisfactory Vaccination Responses Against 3 Antigens
Time Frame: 8 weeks
Seroresponse is defined as serconversion or ≥4-fold increase in antibody titers
8 weeks
Satisfactory Vaccination Responses Against > 2/3 Antigens
Time Frame: 8 weeks
Seroresponse is defined as serconversion or ≥4-fold increase in antibody titers
8 weeks
Satisfactory Vaccination Responses Against > 1/3 Antigens
Time Frame: 8 weeks
Seroresponse is defined as serconversion or ≥4-fold increase in antibody titers
8 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of Seroprotection Against H1N1
Time Frame: 8 weeks
Seroprotection is defined as antibody titers of ≥40
8 weeks
Proportion of Seroprotection Against H3N2
Time Frame: 8 weeks
Seroprotection is defined as antibody titers of ≥40
8 weeks
Proportion of Seroprotection Against B-Yamagata
Time Frame: 8 weeks
Seroprotection is defined as antibody titers of ≥40
8 weeks
Change From Baseline in Antibody Titer Against H1N1
Time Frame: Day of and 4 weeks after vaccination
Fold change = post-vaccination titer/pre-vaccination titer
Day of and 4 weeks after vaccination
Change From Baseline in Antibody Titer Against H3N2
Time Frame: Day of and 4 weeks after vaccination
Fold change = post-vaccination titer/pre-vaccination titer
Day of and 4 weeks after vaccination
Change From Baseline in Antibody Titer Against B-Yamagata
Time Frame: Day of and 4 weeks after vaccination
Fold change = post-vaccination titer/pre-vaccination titer
Day of and 4 weeks after vaccination
DAS28 Flare Rate at Visit 4
Time Frame: 20 weeks from enrollment.
DAS28 flare rate at visit 4 as compared to visit 1. RA flare was defined as an increase in DAS28 of >1.2 (or >0.6 if the baseline DAS28 was ≥3.2).
20 weeks from enrollment.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Seoul National University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2015

Primary Completion (Actual)

August 1, 2016

Study Completion (Actual)

August 1, 2016

Study Registration Dates

First Submitted

September 8, 2015

First Submitted That Met QC Criteria

April 19, 2016

First Posted (Estimate)

April 22, 2016

Study Record Updates

Last Update Posted (Actual)

October 4, 2018

Last Update Submitted That Met QC Criteria

November 29, 2017

Last Verified

November 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SNUH-IMJ-001

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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