MTX Discontinuation and Vaccine Response

NCT02748785 | Completed Phase 4 Results DMC

• 1 other identifier: SNUH-IMJ-001
• Study Type: interventional
• Target: 277
• Locations: 1 country
• Sites: 1

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.

Conditions

Arthritis, Rheumatoid

Outcome Measures

Primary Outcomes (3)

• Satisfactory Vaccination Responses Against 3 Antigens

  Seroresponse is defined as serconversion or ≥4-fold increase in antibody titers

  8 weeks

• Satisfactory Vaccination Responses Against > 2/3 Antigens

  Seroresponse is defined as serconversion or ≥4-fold increase in antibody titers

  8 weeks

• Satisfactory Vaccination Responses Against > 1/3 Antigens

  Seroresponse is defined as serconversion or ≥4-fold increase in antibody titers

  8 weeks

Secondary Outcomes (7)

• Proportion of Seroprotection Against H1N1

  8 weeks

• Proportion of Seroprotection Against H3N2

  8 weeks

• Proportion of Seroprotection Against B-Yamagata

  8 weeks

• Change From Baseline in Antibody Titer Against H1N1

  Day of and 4 weeks after vaccination

• Change From Baseline in Antibody Titer Against H3N2

  Day of and 4 weeks after vaccination

Study Arms (4)

Group 1 (No MTX Hold before Vaccination)

EXPERIMENTAL

Group 1 will continue MTX

Drug: Methotrexate; Biological: Seasonal Influenza vaccine

Group 2 (MTX hold 4 Weeks before vaccination)

EXPERIMENTAL

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

Drug: Methotrexate; Biological: Seasonal Influenza vaccine

Group 3 (MTX hold 2 Weeks before Vaccination)

EXPERIMENTAL

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

Drug: Methotrexate; Biological: Seasonal Influenza vaccine

Group 4 (MTX hold on Day of Vaccination)

EXPERIMENTAL

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

Drug: Methotrexate; Biological: Seasonal Influenza vaccine

Interventions

Methotrexate DRUG

Methotrexate will be continued

Group 1 (No MTX Hold before Vaccination); Group 2 (MTX hold 4 Weeks before vaccination); Group 3 (MTX hold 2 Weeks before Vaccination); Group 4 (MTX hold on Day of Vaccination)

Seasonal Influenza vaccine BIOLOGICAL

all subjects will be vaccinated with a seasonal influenza vaccine

Group 1 (No MTX Hold before Vaccination); Group 2 (MTX hold 4 Weeks before vaccination); Group 3 (MTX hold 2 Weeks before Vaccination); Group 4 (MTX hold on Day of Vaccination)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Seoul National University Hospital: lead

Study Sites (1)

Seoul National University Hospital

Seoul, 110-744, South Korea

Location

Related Publications (4)

• Doran MF, Crowson CS, Pond GR, O'Fallon WM, Gabriel SE. Frequency of infection in patients with rheumatoid arthritis compared with controls: a population-based study. Arthritis Rheum. 2002 Sep;46(9):2287-93. doi: 10.1002/art.10524.

  PMID: 12355475 BACKGROUND

• McMahan ZH, Bingham CO 3rd. Effects of biological and non-biological immunomodulatory therapies on the immunogenicity of vaccines in patients with rheumatic diseases. Arthritis Res Ther. 2014 Dec 23;16(6):506. doi: 10.1186/s13075-014-0506-0.

  PMID: 25587634 BACKGROUND

• Winthrop KL, Silverfield J, Racewicz A, Neal J, Lee EB, Hrycaj P, Gomez-Reino J, Soma K, Mebus C, Wilkinson B, Hodge J, Fan H, Wang T, Bingham CO 3rd. The effect of tofacitinib on pneumococcal and influenza vaccine responses in rheumatoid arthritis. Ann Rheum Dis. 2016 Apr;75(4):687-95. doi: 10.1136/annrheumdis-2014-207191. Epub 2015 Mar 20.

  PMID: 25795907 BACKGROUND

• Park JK, Lee MA, Lee EY, Song YW, Choi Y, Winthrop KL, Lee EB. Effect of methotrexate discontinuation on efficacy of seasonal influenza vaccination in patients with rheumatoid arthritis: a randomised clinical trial. Ann Rheum Dis. 2017 Sep;76(9):1559-1565. doi: 10.1136/annrheumdis-2017-211128. Epub 2017 May 3.

  PMID: 28468794 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Methotrexate

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Eun Bong Lee
• Organization: Seoul National University Hospital

leb7616@snu.ac.kr

+82-2-2072-4399

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 8, 2015
• First Posted: April 22, 2016
• Study Start: September 1, 2015
• Primary Completion: August 1, 2016
• Study Completion: August 1, 2016
• Last Updated: October 4, 2018
• Results First Posted: October 4, 2018

Record last verified: 2017-11

Locations

KR (1)