Rheumatoid Arthritis2 wk MTXNCT02897011
2-week dc of MTX and Influenza Vaccination in RA
A study testing Methotrexate in people with Rheumatoid Arthritis and Influenza, run by Seoul National University Hospital at 3 sites in South Korea.
Trial summary
To investigate whether a transient discontinuation of methotrexate MTX for 2 weeks improves the vaccination response to a seasonal influenza. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Rheumatoid Arthritis, Influenza, Methotrexate
- What is being tested?
- Methotrexate
- Type of treatment
- Vaccines
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 318 participants
- Where
- 3 sitesSouth Korea
- Study dates
- Sep 2016to Aug 2017
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 10Show fewer
- 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
Trial locations and contacts
3 sites in 1 country.
South Korea3 sites, 3 recruiting
- Recruiting
Seoul National Univ. Bundang Hospital
Bundang, Gyeonggi-do, 463-870
Yun Jong Lee, MD PhD, +82-31-787-4051, leeyn35@gmail.com
Yun Jong Lee, MD PhD
- Recruiting
Seoul National University Hospital
Seoul, Seoul, 110-744
Eun Bong Lee, MD PhD, 82-2-2072-3944, leb7616@snu.ac.kr
Hyun Mi Kwon, MD, 82-2-2072-3198, hmikwon@gmail.com
- Recruiting
SMG-SNU Boramae Medical Center
Seoul, Seoul, 156-707
Kichul Shin, MD PhD, +82-2-870-3204, kideb1@snu.ac.kr
Kichul Shin, MD PhD
About this study
Official title: Effect of Two-week Discontinuation of Methotrexate on Efficacy of Seasonal Influenza Vaccination in Patients With Rheumatoid Arthritis: A Randomized Clinical Trial
To investigate whether a transient discontinuation of methotrexate MTX for 2 weeks improves the vaccination response to a seasonal influenza.
Read the 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.
- Conditions
- Rheumatoid Arthritis, Influenza, Methotrexate
- Being tested
- Methotrexate
- Medical subject headings
- Arthritis, Rheumatoid, Influenza, Human
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MethotrexateDrug
| Study group | Role | What they receive |
|---|---|---|
| Group 1: MTX continue | Sham comparator | Group will continue MTX after vaccination Receives: Drug: Methotrexate |
| Group 2: MTX hold | Experimental | will hold MTX for 2 weeks after vaccination Receives: Drug: Methotrexate |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 4 weeks
Secondary outcomes (5)
Proportion of patients who have ≥ 4-fold increase in post-vaccination titer in ≥ 3 of 4 influenza strains
Measured: 4 weeks
Proportion of seroprotection for each strain
Measured: 4 weeks
Change from baseline in titer (in GMT) for each strain
Measured: 4 weeks
Change from baseline in DAS28-4 (CRP) at 4 weeks after vaccination
Measured: 4 weeks
Proportion of patients who experience increase in disease activity
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Sep 2016 (estimated)
- Study startSep 2016
- Primary completionAug 2017 (estimated)
- Study completionAug 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- More trials run by Seoul National University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 318 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Seoul National University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Eun Bong Lee, Seoul National University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02897011
- Sponsor's protocol ID
- SNUH-IMJ-003
- Acronym
- 2 wk MTX
- Status last verified
- Oct 2016
- First submitted
- 7 Sep 2016
- Last updated
- 27 Oct 2016
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Publications
Park JK, Choi Y, Winthrop KL, Song YW, Lee EB. Optimal time between the last methotrexate administration and seasonal influenza vaccination in rheumatoid arthritis: post hoc analysis of a randomised clinical trial. Ann Rheum Dis. 2019 Sep;78(9):1283-1284. doi: 10.1136/annrheumdis-2019-215187. Epub 2019 Mar 23. No abstract available.
PubMed 30904830Park 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.
PubMed 29572291
Study at a glance
From the registry record, last updated by the sponsor on 27 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Two-week Discontinuation of Methotrexate on Efficacy of Seasonal Influenza Vaccination in Patients With Rheumatoid Arthritis: A Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT02897011
- Acronym / sponsor ID
- 2 wk MTX / SNUH-IMJ-003
- Conditions
- Rheumatoid Arthritis, Influenza, Methotrexate
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 318 participants (estimated)
- Lead sponsor
- Seoul National University HospitalUniversity, hospital or other
- Study start
- Sep 2016
- Primary completion
- Aug 2017 (estimated)
- Study completion
- Aug 2017 (estimated)
- First posted
- 12 Sep 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To investigate whether a transient discontinuation of methotrexate MTX for 2 weeks improves the vaccination response to a seasonal influenza.
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1: MTX continue | Sham comparator | Drug: MethotrexateGroup will continue MTX after vaccination |
| Group 2: MTX hold | Experimental | Drug: Methotrexatewill hold MTX for 2 weeks after vaccination |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Methotrexate | Drug | Group 1: MTX continue, Group 2: MTX hold |
Primary outcome
Proportion of satisfactory vaccine response
Time frame: 4 weeks
Proportion of satisfactory vaccine response that is defined as ≥ 4-fold increase in post-vaccination titer in ≥ 2 of 4 influenza strains
5 secondary outcomes
Proportion of patients who have ≥ 4-fold increase in post-vaccination titer in ≥ 3 of 4 influenza strains
Time frame: 4 weeks
Proportion of seroprotection for each strain
Time frame: 4 weeks
Change from baseline in titer (in GMT) for each strain
Time frame: 4 weeks
Change from baseline in DAS28-4 (CRP) at 4 weeks after vaccination
Time frame: 4 weeks
Proportion of patients who experience increase in disease activity
Time frame: 4 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Oct 2016.
- Derived from this study: PubMed 30904830Park JK, Choi Y, Winthrop KL, Song YW, Lee EB. Optimal time between the last methotrexate administration and seasonal influenza vaccination in rheumatoid arthritis: post hoc analysis of a randomised clinical trial. Ann Rheum Dis. 2019 Sep;78(9):1283-1284. doi: 10.1136/annrheumdis-2019-215187. Epub 2019 Mar 23. No abstract available.
- Derived from this study: PubMed 29572291Park 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.
- Individual participant dataSharing planned: Undecided
Related trials for Rheumatoid Arthritis
RecruitingPhase 2
Study of PTC844 in Participants With Active Rheumatoid Arthritis
Rheumatoid Arthritis
Not yet recruitingPhase 1
An Ascending Dose Study of DKB903 in Participants With Rheumatoid Arthritis (RA) and Participants With Systemic Lupus Erythematosus (SLE)
Rheumatoid Arthritis and Systemic Lupus Erythematosus
Not yet recruitingPhase 1
R-2487 in Patients With Sjogren's Syndrome (SjD)
Sjogren's Syndrome, Sjögren
RecruitingPhase 1
A Trial in Healthy Adult Participants and Adults With Autoimmune Diseases to Test How HBM7020 is Tolerated and How it Behaves in the Body
Rheumatoid Arthritis, Systemic Lupus Erythematosus
Active, not recruitingPhase 2
A Study Evaluating the Safety and Efficacy of Inhaled AP01 in Participants With Progressive Pulmonary Fibrosis
Pulmonary Fibrosis, Progressive Pulmonary Fibrosis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Methotrexate in people with Rheumatoid Arthritis and Influenza, run by Seoul National University Hospital at 3 sites in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 27 Oct 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of satisfactory vaccine response (time frame: 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02897011, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Oct 2016.