MTX Discontinuation and Vaccine Response

Seoul National University

Status and phase: Completed; Phase 4

Conditions: Arthritis, Rheumatoid

Treatments: Drug: Methotrexate; Biological: Seasonal Influenza vaccine

Study type: Interventional

Funder types: Other

Identifiers

NCT02748785

SNUH-IMJ-001

Details and patient eligibility

About

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.

Full 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.

Enrollment: 277 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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277 participants in 4 patient groups

Group 1 (No MTX Hold before Vaccination)

Experimental group

Description:

Group 1 will continue MTX

Treatment:

Biological: Seasonal Influenza vaccine

Drug: Methotrexate

Group 2 (MTX hold 4 Weeks before vaccination)

Experimental group

Description:

Group 2 will hold MTX 4 weeks before vaccination and resume MTX on the day of vaccination

Treatment:

Biological: Seasonal Influenza vaccine

Drug: Methotrexate

Group 3 (MTX hold 2 Weeks before Vaccination)

Experimental group

Description:

Group 3 will hold MTX 2 weeks before vaccination and resume MTX 2 weeks after vaccination

Treatment:

Biological: Seasonal Influenza vaccine

Drug: Methotrexate

Group 4 (MTX hold on Day of Vaccination)

Experimental group

Description:

Group 4 will hold MTX on day of vaccination and resume MTX 4 weeks after vaccination.

Treatment:

Biological: Seasonal Influenza vaccine

Drug: Methotrexate