Conditions: Arthritis, Rheumatoid
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 277
Healthy volunteers: no

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.

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.

Arms:
arm 1: Group 1 will continue MTX arm 2: Group 2 will hold MTX 4 weeks before vaccination and resume MTX on the day of vaccination arm 3: Group 3 will hold MTX 2 weeks before vaccination and resume MTX 2 weeks after vaccination arm 4: Group 4 will hold MTX on day of vaccination and resume MTX 4 weeks after vaccination.

Interventions: intervention 1: Methotrexate intervention 2: Seasonal Influenza vaccine
Intervention descriptions: intervention 1: Methotrexate will be continued intervention 2: all subjects will be vaccinated with a seasonal influenza vaccine

Protocol document: