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Arthritis, RheumatoidPhase 4NCT02748785

MTX Discontinuation and Vaccine Response

A Phase 4 study testing Methotrexate and Seasonal Influenza vaccine in people with Arthritis, Rheumatoid, run by Seoul National University Hospital at 1 site in South Korea.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Arthritis, Rheumatoid
What is being tested?
Methotrexate and Seasonal Influenza vaccine
Type of treatment
Vaccines
Could I receive a placebo?
No, everyone receives an active treatment
How many people
277 participants
Where
1 siteSouth Korea
Study dates
Sep 2015to Aug 2016
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

South Korea1 site

  • Seoul National University Hospital

    Seoul, 110-744

Other trials in South Korea

About this study

Official title: 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.

Read the 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.

Being tested
Methotrexate, Seasonal Influenza vaccine
Medical subject headings
Arthritis, Rheumatoid

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MethotrexateDrug

    Methotrexate will be continued

  • Seasonal Influenza vaccineBiological

    all subjects will be vaccinated with a seasonal influenza vaccine

Study groups in NCT02748785
Study groupRoleWhat they receive
Group 1 (No MTX Hold before Vaccination)ExperimentalGroup 1 will continue MTX
Receives: Drug: Methotrexate; Biological: Seasonal Influenza vaccine
Group 2 (MTX hold 4 Weeks before vaccination)ExperimentalGroup 2 will hold MTX 4 weeks before vaccination and resume MTX on the day of vaccination
Receives: Drug: Methotrexate; Biological: Seasonal Influenza vaccine
Group 3 (MTX hold 2 Weeks before Vaccination)ExperimentalGroup 3 will hold MTX 2 weeks before vaccination and resume MTX 2 weeks after vaccination
Receives: Drug: Methotrexate; Biological: Seasonal Influenza vaccine
Group 4 (MTX hold on Day of Vaccination)ExperimentalGroup 4 will hold MTX on day of vaccination and resume MTX 4 weeks after vaccination.
Receives: Drug: Methotrexate; Biological: Seasonal Influenza vaccine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Satisfactory Vaccination Responses Against 3 Antigens

    Seroresponse is defined as serconversion or ≥4-fold increase in antibody titers

    Measured: 8 weeks

  2. Satisfactory Vaccination Responses Against > 2/3 Antigens

    Seroresponse is defined as serconversion or ≥4-fold increase in antibody titers

    Measured: 8 weeks

  3. Satisfactory Vaccination Responses Against > 1/3 Antigens

    Seroresponse is defined as serconversion or ≥4-fold increase in antibody titers

    Measured: 8 weeks

Secondary outcomes (7)

  1. Proportion of Seroprotection Against H1N1

    Seroprotection is defined as antibody titers of ≥40

    Measured: 8 weeks

  2. Proportion of Seroprotection Against H3N2

    Seroprotection is defined as antibody titers of ≥40

    Measured: 8 weeks

  3. Proportion of Seroprotection Against B-Yamagata

    Seroprotection is defined as antibody titers of ≥40

    Measured: 8 weeks

  4. Change From Baseline in Antibody Titer Against H1N1

    Fold change = post-vaccination titer/pre-vaccination titer

    Measured: Day of and 4 weeks after vaccination

  5. Change From Baseline in Antibody Titer Against H3N2

    Fold change = post-vaccination titer/pre-vaccination titer

    Measured: Day of and 4 weeks after vaccination

  6. Change From Baseline in Antibody Titer Against B-Yamagata

    Fold change = post-vaccination titer/pre-vaccination titer

    Measured: Day of and 4 weeks after vaccination

  7. DAS28 Flare Rate at Visit 4

    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).

    Measured: 20 weeks from enrollment.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Apr 2016 (estimated)
  2. Study startSep 2015
  3. Primary completionAug 2016
  4. Study completionAug 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
277 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02748785
Sponsor's protocol ID
SNUH-IMJ-001
Status last verified
Nov 2017
First submitted
8 Sep 2015
Last updated
4 Oct 2018
Data monitoring committee
Yes

Publications

  • Doran MF, Crowson CS, Pond GR, O'Fallon WM, Gabriel SE. Frequency of infection in patients with rheumatoid arthritis compared with controls: a population-based study. Arthritis Rheum. 2002 Sep;46(9):2287-93. doi: 10.1002/art.10524.

    PubMed 12355475

  • McMahan ZH, Bingham CO 3rd. Effects of biological and non-biological immunomodulatory therapies on the immunogenicity of vaccines in patients with rheumatic diseases. Arthritis Res Ther. 2014 Dec 23;16(6):506. doi: 10.1186/s13075-014-0506-0.

    PubMed 25587634

  • Winthrop KL, Silverfield J, Racewicz A, Neal J, Lee EB, Hrycaj P, Gomez-Reino J, Soma K, Mebus C, Wilkinson B, Hodge J, Fan H, Wang T, Bingham CO 3rd. The effect of tofacitinib on pneumococcal and influenza vaccine responses in rheumatoid arthritis. Ann Rheum Dis. 2016 Apr;75(4):687-95. doi: 10.1136/annrheumdis-2014-207191. Epub 2015 Mar 20.

    PubMed 25795907

  • Park JK, Lee MA, Lee EY, Song YW, Choi Y, Winthrop KL, Lee EB. Effect of methotrexate discontinuation on efficacy of seasonal influenza vaccination in patients with rheumatoid arthritis: a randomised clinical trial. Ann Rheum Dis. 2017 Sep;76(9):1559-1565. doi: 10.1136/annrheumdis-2017-211128. Epub 2017 May 3.

    PubMed 28468794

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Methotrexate and Seasonal Influenza vaccine in people with Arthritis, Rheumatoid, run by Seoul National University Hospital at 1 site in South Korea.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 Oct 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Satisfactory Vaccination Responses Against 3 Antigens (time frame: 8 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02748785, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Oct 2018.

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