2 wk MTX: 2-week dc of MTX and Influenza Vaccination in RA

Sponsor

Seoul National University Hospital (Other)

Overall Status

Unknown status

CT.gov ID

NCT02897011

Collaborator

(none)

318

Enrollment

Locations

Arms

Duration (Months)

106

Patients Per Site

9.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis Influenza Methotrexate	Drug: Methotrexate	N/A

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 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

318 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Sep 1, 2016

Anticipated Primary Completion Date :

Aug 1, 2017

Anticipated Study Completion Date :

Aug 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Sham Comparator: Group 1: MTX continue Group will continue MTX after vaccination	Drug: Methotrexate
Experimental: Group 2: MTX hold will hold MTX for 2 weeks after vaccination	Drug: Methotrexate

Arm

Intervention/Treatment

Sham Comparator: Group 1: MTX continue

Group will continue MTX after vaccination

Drug: Methotrexate

Experimental: Group 2: MTX hold

will hold MTX for 2 weeks after vaccination

Drug: Methotrexate

Outcome Measures

Primary Outcome Measures

Proportion of satisfactory vaccine response [4 weeks]
Proportion of satisfactory vaccine response that is defined as ≥ 4-fold increase in post-vaccination titer in ≥ 2 of 4 influenza strains

Secondary Outcome Measures

Proportion of patients who have ≥ 4-fold increase in post-vaccination titer in ≥ 3 of 4 influenza strains [4 weeks]
Proportion of seroprotection for each strain [4 weeks]
Change from baseline in titer (in GMT) for each strain [4 weeks]
Change from baseline in DAS28-4 (CRP) at 4 weeks after vaccination [4 weeks]
Proportion of patients who experience increase in disease activity [4 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Seoul National Univ. Bundang Hospital	Bundang	Gyeonggi-do	Korea, Republic of	463-870
2	Seoul National University Hospital	Seoul		Korea, Republic of	110-744
3	SMG-SNU Boramae Medical Center	Seoul		Korea, Republic of	156-707

Sponsors and Collaborators

Seoul National University Hospital

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Eun Bong Lee, Professor, Seoul National University Hospital

ClinicalTrials.gov Identifier:

NCT02897011

Other Study ID Numbers:

SNUH-IMJ-003

First Posted:

Sep 12, 2016

Last Update Posted:

Oct 27, 2016

Last Verified:

Oct 1, 2016

Individual Participant Data (IPD) Sharing Statement:

Undecided

Plan to Share IPD:

Undecided

Additional relevant MeSH terms:

Influenza, Human

Arthritis

Arthritis, Rheumatoid

Methotrexate

Study Results

No Results Posted as of Oct 27, 2016