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MTX Discontinuation and Vaccine Response

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ClinicalTrials.gov Identifier: NCT02748785
Recruitment Status : Completed
First Posted : April 22, 2016
Results First Posted : October 4, 2018
Last Update Posted : October 4, 2018
Sponsor:
Information provided by (Responsible Party):
Eun Bong Lee, Seoul National University Hospital

Brief 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.

Condition or disease Intervention/treatment Phase
Arthritis, Rheumatoid Drug: Methotrexate Biological: Seasonal Influenza vaccine Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 277 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Effect of Methotrexate Discontinuation on Efficacy of Seasonal Influenza Vaccination in Patients With Rheumatoid Arthritis: A Randomized Clinical Trial
Study Start Date : September 2015
Actual Primary Completion Date : August 2016
Actual Study Completion Date : August 2016

Resource links provided by the National Library of Medicine


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




Primary Outcome Measures :
  1. Satisfactory Vaccination Responses Against 3 Antigens [ Time Frame: 8 weeks ]
    Seroresponse is defined as serconversion or ≥4-fold increase in antibody titers

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

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


Secondary Outcome Measures :
  1. Proportion of Seroprotection Against H1N1 [ Time Frame: 8 weeks ]
    Seroprotection is defined as antibody titers of ≥40

  2. Proportion of Seroprotection Against H3N2 [ Time Frame: 8 weeks ]
    Seroprotection is defined as antibody titers of ≥40

  3. Proportion of Seroprotection Against B-Yamagata [ Time Frame: 8 weeks ]
    Seroprotection is defined as antibody titers of ≥40

  4. 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

  5. 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

  6. 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

  7. 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).



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02748785


Locations
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Korea, Republic of
Seoul National University Hospital
Seoul, Korea, Republic of, 110-744
Sponsors and Collaborators
Seoul National University Hospital
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Eun Bong Lee, Professor, Seoul National University Hospital
ClinicalTrials.gov Identifier: NCT02748785    
Other Study ID Numbers: SNUH-IMJ-001
First Posted: April 22, 2016    Key Record Dates
Results First Posted: October 4, 2018
Last Update Posted: October 4, 2018
Last Verified: November 2017
Additional relevant MeSH terms:
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Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Methotrexate
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors