One or Two Week Methotrexate Discontinuation on Efficacy of Influenza Vaccination in Rheumatoid Arthritis.

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

This is a multi-center, randomized, single-blinded, prospective, parallel group intervention study to investigate whether methotrexate (MTX) discontinuation for 1 week is non-inferior to MTX discontinuation for 2 weeks in regard to satisfactory vaccination response to a seasonal influenza.

Study Overview

• Status: Completed
• Conditions: Autoimmune Diseases; Rheumatoid Arthritis; Vaccine Reaction; Influenza
• Intervention / Treatment: Drug: MTX-hold

• Study Type: Interventional
• Enrollment (Actual): 184
• Phase: Phase 3

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 156-707
    • SMG-SNU Boramae Medical Center
  • Gyeonggi-do
    • Seongnam-si, Gyeonggi-do, Korea, Republic of, 13620
      • Seoul National Univ. Bundang Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Males or females ≥ 19 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
• Blood transfusion within 6 months
• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MTX 1 week hold; Patients who will hold MTX for 1 week after an influenza vaccine.	Drug: MTX-hold; Temporary discontinuation of methotrexate for 1 or 2 weeks
Active Comparator: MTX 2 week hold; Patients who will hold MTX for 2 weeks after an influenza vaccine.	Drug: MTX-hold; Temporary discontinuation of methotrexate for 1 or 2 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of satisfactory vaccine response	as ≥ 4-fold increase in post-vaccination titer in ≥ 2 of 4 influenza strains at 4 weeks after vaccination	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportio0n of patients who have ≥ 4-fold increase in post-vaccination titer in ≥ 3 of 4 influenza strains	Proportion of patients who have ≥ 4-fold increase in post-vaccination titer in ≥ 3 of 4 influenza strains at 4 weeks and 16 weeks after vaccination	4 weeks and 16 weeks
Proportion of seroprotection for each strain		4 weeks and 16 weeks
Change from baseline in titer (in GMT)		4 weeks and 16 weeks
Change from baseline in DAS28-4 (CRP)		4 weeks and 16 weeks
Disease flare		4 weeks and 16 weeks

Collaborators and Investigators

• Sponsor: Seoul National University Hospital

Publications and helpful links

General Publications

• Park JK, Kim MJ, Choi Y, Winthrop K, Song YW, Lee EB. Effect of short-term methotrexate discontinuation on rheumatoid arthritis disease activity: post-hoc analysis of two randomized trials. Clin Rheumatol. 2020 Feb;39(2):375-379. doi: 10.1007/s10067-019-04857-y. Epub 2019 Dec 10.
• Park JK, Lee YJ, Shin K, Ha YJ, Lee EY, Song YW, Choi Y, Winthrop KL, Lee EB. Impact of temporary methotrexate discontinuation for 2 weeks on immunogenicity of seasonal influenza vaccination in patients with rheumatoid arthritis: a randomised clinical trial. Ann Rheum Dis. 2018 Jun;77(6):898-904. doi: 10.1136/annrheumdis-2018-213222. Epub 2018 Mar 23.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2021
• Primary Completion (Actual): September 30, 2022
• Study Completion (Actual): September 30, 2022

Study Registration Dates

• First Submitted: September 26, 2021
• First Submitted That Met QC Criteria: September 26, 2021
• First Posted (Actual): October 6, 2021

Study Record Updates

• Last Update Posted (Actual): December 16, 2022
• Last Update Submitted That Met QC Criteria: December 14, 2022
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: rheumatoid arthritis; influenza; methotrexate
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Immune System Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Orthomyxoviridae Infections; Arthritis; Arthritis, Rheumatoid; Influenza, Human; Autoimmune Diseases
• Other Study ID Numbers: 2109-020-1252

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No