2-week dc of MTX and Influenza Vaccination in RA

Rheumatoid Arthritis Clinical Trial

— 2 wk MTX  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02897011
• Other study ID #: SNUH-IMJ-003
• Status: Recruiting
• Phase: N/A
• First received: September 7, 2016
• Last updated: October 26, 2016
• Start date: September 2016
• Est. completion date: August 2017

Study information

• Verified date: October 2016
• Source: Seoul National University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Seoul National University Hospital: IRB
• Study type: Interventional

Clinical Trial Summary

To investigate whether a transient discontinuation of methotrexate MTX for 2 weeks improves the vaccination response to a seasonal influenza.

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 antirheumatic 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 of the preventive diseases is crucial and recommended in all patients unless contraindicated.

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 MTX at the time of when vaccinations. To improve the vaccine response, a short term discontinuation of MTX could be considered. In a prior study, we discovered that a temporary discontinuation of MTX for 4 weeks during peri-vaccination period tended to be associated with an improved response to vaccination with trivalent influenza vaccination (Figure 1). It remains to be defined whether MTX discontinuation for shorter period increases the vaccination efficacy while minimizing the RA flare rate.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 318
• Est. completion date: August 2017
• Est. primary completion date: August 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Males or females = 19 years and < 65 years of age 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

• Any condition including laboratory abnormality which places the subject at unacceptable risk

• Subjects who decline to participate

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Influenza
• Influenza, Human
• Methotrexate
• Rheumatoid Arthritis

Intervention

Drug:
• Methotrexate

Locations

Country	Name	City	State
Korea, Republic of	Seoul National Univ. Bundang Hospital	Bundang	Gyeonggi-do
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	SMG-SNU Boramae Medical Center	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Seoul National University Hospital

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of satisfactory vaccine response	Proportion of satisfactory vaccine response that is defined as = 4-fold increase in post-vaccination titer in = 2 of 4 influenza strains	4 weeks	No
Secondary	Proportion of patients who have = 4-fold increase in post-vaccination titer in = 3 of 4 influenza strains		4 weeks	No
Secondary	Proportion of seroprotection for each strain		4 weeks	No
Secondary	Change from baseline in titer (in GMT) for each strain		4 weeks	No
Secondary	Change from baseline in DAS28-4 (CRP) at 4 weeks after vaccination		4 weeks	No
Secondary	Proportion of patients who experience increase in disease activity		4 weeks	No