MTX Discontinuation and Vaccine Response

Arthritis, Rheumatoid Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02748785
• Other study ID #: SNUH-IMJ-001
• Status: Completed
• Phase: Phase 4
• Start date: September 2015
• Est. completion date: August 2016

Study information

• Verified date: November 2017
• Source: Seoul National University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 277
• Est. completion date: August 2016
• Est. primary completion date: August 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid

Intervention

Drug:
• Methotrexate
Methotrexate will be continued

Biological:
• Seasonal Influenza vaccine
all subjects will be vaccinated with a seasonal influenza vaccine

Locations

Country	Name	City	State
Korea, Republic of	Seoul National University Hospital	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Seoul National University Hospital

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (3)

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. — View Citation

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. Review. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Satisfactory Vaccination Responses Against 3 Antigens	Seroresponse is defined as serconversion or =4-fold increase in antibody titers	8 weeks
Primary	Satisfactory Vaccination Responses Against > 2/3 Antigens	Seroresponse is defined as serconversion or =4-fold increase in antibody titers	8 weeks
Primary	Satisfactory Vaccination Responses Against > 1/3 Antigens	Seroresponse is defined as serconversion or =4-fold increase in antibody titers	8 weeks
Secondary	Proportion of Seroprotection Against H1N1	Seroprotection is defined as antibody titers of =40	8 weeks
Secondary	Proportion of Seroprotection Against H3N2	Seroprotection is defined as antibody titers of =40	8 weeks
Secondary	Proportion of Seroprotection Against B-Yamagata	Seroprotection is defined as antibody titers of =40	8 weeks
Secondary	Change From Baseline in Antibody Titer Against H1N1	Fold change = post-vaccination titer/pre-vaccination titer	Day of and 4 weeks after vaccination
Secondary	Change From Baseline in Antibody Titer Against H3N2	Fold change = post-vaccination titer/pre-vaccination titer	Day of and 4 weeks after vaccination
Secondary	Change From Baseline in Antibody Titer Against B-Yamagata	Fold change = post-vaccination titer/pre-vaccination titer	Day of and 4 weeks after vaccination
Secondary	DAS28 Flare Rate at Visit 4	DAS28 flare rate at visit 4 as compared to visit 1. RA flare was defined as an increase in DAS28 of >1.2 (or >0.6 if the baseline DAS28 was =3.2).	20 weeks from enrollment.