Rheumatoid Arthritis (RA)Phase 4DISCONCT07802678
Discontinuation of Disease-modifying Anti-rheumatic Drugs (DMARDs) in Rheumatoid Arthritis Patients Also Using TNF Inhibitors
A Phase 4 study testing Strategy to attempt discontinuation of MTX or LEF (and restart when necessary) and Continuation of MTX or LEF in people with Rheumatoid Arthritis (RA), run by Sint Maartenskliniek at 4 sites in Netherlands.
Trial summary
The goal is to investigate whether a strategy of attempting to discontinue of MTX or LEF (and restart when necessary) in RA patients treated with an optimal dose (allowed dose or lower, tapered to the maximum, or according to patient preference) TNFi is not worser to a continuation of combination therapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rheumatoid Arthritis (RA)
- What is being tested?
- Strategy to attempt discontinuation of MTX or LEF (and restart when necessary) and Continuation of MTX or LEF
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 202 participants
- Where
- 4 sitesNetherlands
- Study dates
- 14 Jul 2026to 1 May 2029
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years.
- Diagnosis of RA, according to the 2010 ACR/EULAR and/or 1987 RA classification criteria or clinical diagnosis by a rheumatologist.
- Stable disease activity for ≥ 6 months, defined as DAS28-CRP ≤ 2.9 or DAS28-CRP ≤ 3.5 combined with clinical judgment of LDA.
- Current combination therapy consisting of TNFi and either MTX or LEF.
- TNFi administration at a stable dose (at an optimal dose, defined as the authorized dose or lower and being maximally tapered, because of prior disease flare or patient preference) for ≥6 months prior to screening, during which LDA is maintained for ≥6 months.
- MTX or LEF administration at a stable dose for ≥3 months prior to screening.
- Ability to comply with all study procedures, visits and follow-up assessments.
- Written informed consent provided prior to any study-related procedure.
Who cannot join
- A previous attempt within the last 12 months prior to screening to taper or discontinue MTX or LEF that required reintroduction or dose increase of the csDMARD due to a disease flare.
- Current MTX or LEF treatment for other indications than RA.
- Current treatment with prednisolone (equivalent) of > 5 mg per day.
- Current severe comorbidity or serious life-shortening condition that could interfere with adherence to the study protocol or completion of the 24-month follow-up period.
- Women that are pregnant, breast feeding or considering pregnancy during the study period (MTX and LEF are contraindicated in pregnancy and breastfeeding).
- Inability to comply with the study procedures, visits, or follow-up assessments.
- Inability or unwillingness to provide informed consent.
Trial locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Netherlands4 sites, 4 recruiting
- Not yet recruiting
Reade Amsterdam
Amsterdam, North Holland, 1056 AA
Sadaf Atiqi, MSc., ++ 0202421000, s.atiqi@reade.nl
- Recruiting
Sint Maartenskliniek
Nijmegen, Gelderland, 6574NA
Alfons den Broeder, Dr., ++ 31 24 365 9279, a.denbroeder@maartenskliniek.nl
- Not yet recruiting
Erasmus MC
Rotterdam, South Holland, 3015GJ
Pascal de Jonge, Dr., ++ 31653995477, p.h.p.dejong@erasmusmc.nl
- Not yet recruiting
Elisabeth-TweeSteden Ziekenhuis Tilburg
Tilburg, North Brabant, 5022 GC
Lydia Schipper, Dr., ++ 0132210380, l.schipper@etz.nl
About this study
Official title: DISCO: DIScontinuation of COncomitant Disease Modifying Anti-rheumatic Drugs (DMARDs) in Rheumatoid Arthritis Patients Also Using TNF Inhibitors - a Randomized Long-term Non-inferiority Strategy Trial
The goal is to investigate whether a strategy of attempting to discontinue of MTX or LEF (and restart when necessary) in RA patients treated with an optimal dose (allowed dose or lower, tapered to the maximum, or according to patient preference) TNFi is not worser to a continuation of combination therapy. The study will also examine the disease-related effects of treatment that attempts to discontinue MTX or LEF, how patients experience it, its safety, and its impact on medication usage and healthcare costs.
The main outcome is the difference between treatments in average disease activity over 24 months. The study will compare whether disease activity remains similar between patients who attempt to discontinue MTX or LEF and those who continue combination therapy.
Patients will be followed for 24 months with scheduled hospital visits at baseline, after 3, 6, 12, 18, and 24 months, remote visits, and additional visits for disease flares. X-rays of the hands and feet will be taken at baseline and after 24 months. During some visits, additional blood samples will be taken to measure inflammation markers and medication levels.
Read the detailed description
Rationale Rheumatoid arthritis (RA) is a long-term inflammatory disease that causes joint pain, swelling, and stiffness. Many patients are treated with a combination of medications to control inflammation. These usually include a biological medicine called a TNF inhibitor (TNFi) and another medicine, methotrexate (MTX) or leflunomide (LEF). Although this combination treatment is effective, patients often experience side effects (such as gastro-intestinal complaints and fatigue), require frequent blood tests, and may experience treatment fatigue from taking multiple medications. Patients would therefore prefer to reduce their medication. The safe reduction of TNFi treatment has been studied before. It is still unclear whether patients can safely discontinue MTX or LEF when their disease is well controlled. This study investigates whether attempting to discontinue MTX or LEF while using a TNF inhibitor is no worse than continuing combination treatment in terms of disease activity, with the hope of reducing side effects, the need for monitoring, and healthcare costs.
Objective The objective is to investigate whether a strategy of attempting to discontinue of MTX or LEF (and restart when necessary) in RA patients treated with an optimal dose (allowed dose or lower, tapered to the maximum, or according to patient preference) TNFi is not worser to a continuation of combination therapy. The study will also examine the disease-related effects of treatment that attempts to discontinue MTX or LEF, how patients experience it, its safety, and its impact on medication usage and healthcare costs.
Main trial endpoints The main endpoint is the difference between treatments in average disease activity over 24 months. The study will compare whether disease activity remains similar between patients who attempt to discontinue MTX or LEF and those who continue combination therapy.
Secondary trial endpoints Other study outcomes include the proportion of patients in the discontinuation strategy group using MTX/LEF and/or a TNFi after 24 months, and differences between treatments in patient-reported outcomes, joint damage measured by X-ray, blood levels of TNF inhibitors, safety and cost-effectiveness.
Trial design This study is being conducted in multiple hospitals. A total of 202 patients with RA will be randomly assigned to stopping MTX/LEF or continuation of combination therapy and followed for 24 months. Two-thirds of the patients will attempt to discontinue MTX or LEF (discontinuation group), and one-third will continue using the combination treatment (continuation group).
Trial population Adult patients aged 18 years and older with RA are eligible to participate if their disease has low disease activity for at least six months during treatment with a TNFi in combination with MTX or LEF.
Interventions In this study, we examine the difference between two groups: the discontinuation group and the continuation group. In the discontinuation group, patients immediately stop taking MTX or LEF and use only the TNFi at a stable dose. When disease activity increases, MTX or LEF can be restarted at the previous dose. If necessary, temporary treatment, such as glucocorticoids, can be administered. In the continuation group, patients continue using combination therapy with MTX or LEF and a TNFi at stable doses. In both groups, the goal is to maintain a stable dose of the TNFi throughout the study. Dosage adjustments or switching to a different biologic drug are permitted if disease activity increases or if side effects occur. These decisions are made by the treating rheumatologist in consultation with the patient.
During the 24-month study, patients continue to receive regular care, including six-monthly check-ups and laboratory tests. An additional study visit takes place after 3 months to detect changes in disease activity at an early stage. In addition, remote visits (by telephone) will take place at 9, 15 and 21 months. Additional visits can be scheduled if a disease flare is suspected.
- Conditions
- Rheumatoid Arthritis (RA)
- Being tested
- Strategy to attempt discontinuation of MTX or LEF (and restart when necessary), Continuation of MTX or LEF
- Keywords
- TNF inhibitors, csDMARDs, Disease activity, Mean-time weighted
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Strategy to attempt discontinuation of MTX or LEF (and restart when necessary)Drug
Participants will discontinue their csDMARD (MTX or LEF) immediately following randomization and continue TNFi monotherapy at their current stable dose.
Continuation of MTX or LEFDrug
Participants will aim to continue combination therapy with csDMARD (MTX or LEF) and TNFi at their current stable doses.
| Study group | Role | What they receive |
|---|---|---|
| csDMARD discontinuation | Experimental | Participants will discontinue their csDMARD (MTX or LEF) immediately following randomization and continue TNFi monotherapy at their current stable dose. Receives: Drug: Strategy to attempt discontinuation of MTX or LEF (and restart when necessary) |
| csDMARD continuation | Active comparator | Participants will aim to continue combination therapy with csDMARD (MTX or LEF) and TNFi at their current stable doses. Receives: Drug: Continuation of MTX or LEF |
What is being measured
The primary outcome is the main question the study is designed to answer.
The between-group difference in mean time-weighted DAS28-CRP during 24 months of follow-up.
The between-group difference in mean time-weighted DAS28-CRP during 24 months of follow-up. A mean time-weighted DAS28-CRP is chosen to balance the limitations of assessing disease activity at a single timepoint with solely considering the occurrence of flare. The time-weighted DAS28-CRP consists of a weighted average of a patient's DAS28-CRP scores, calculated using the trapezoid method and weighed by the time interval between measurements.
Measured: At 24 months of follow-up.
Secondary outcomes (20)
Between-group difference in disease activity
Disease activity measured by DAS28-CRP at 3, 6, 12, 18 and 24 months.
Measured: At 3, 6, 12, 18 and 24 months of follow-up.
Between-group difference at specific timepoint disease activity
Proportion of patients in remission (DAS28-CRP ≤ 2.4) or LDA (DAS28-CRP ≤ 2.9) at 3, 6, 12, 18, and 24 months.
Measured: At 3, 6, 12, 18 and 24 months of follow-up.
Between-group difference in PROM
Fatigue and pain are measured by the Numeric Pain Rating Scale (NRS 0-10), where the minimum value is 0 and the maximum value is 10, meaning higher scores indicate a worse outcome of greater pain intensity and more severe fatigue. This scale is administered at baseline, 3, 6, 12, 18, and 24 months, as well as at flare visits.
Measured: At baseline and 3, 6, 12, 18 and 24 months of follow-up and flare-visits.
Between-group difference in PROM
Disease impact is measured by the Rheumatoid Arthritis Impact of Disease (RAID) Questionnaire, where the minimum value is 0 and the maximum value is 10, meaning higher scores indicate a worse outcome of greater overall disease impact on the patient's life. This questionnaire is administered at baseline, 3, 6, 12, 18, and 24 months, as well as at flare visits.
Measured: At baseline and 3, 6, 12, 18 and 24 months of follow-up and flare-visits.
Between-group difference in PROM
Disease impact is also measured by the Rheumatoid Arthritis Flare Questionnaire (RA-FQ), where the minimum value is 0 and the maximum value is 50, meaning higher scores indicate a worse outcome of a more severe or active disease flare. This questionnaire is administered at baseline, 3, 6, 12, 18, and 24 months, as well as at flare visits.
Measured: At baseline and 3, 6, 12, 18 and 24 months of follow-up and flare-visits.
Between-group difference in PROM
Disease impact is further measured by the Patient Acceptable Symptom State (PASS), where the minimum value is 0 (representing Unacceptable) and the maximum value is 1 (representing Acceptable), meaning higher scores indicate a better outcome where the patient considers their current symptom state to be acceptable. This assessment is completed at baseline, 3, 6, 12, 18, and 24 months, as well as at flare visits.
Measured: At baseline and 3, 6, 12, 18 and 24 months of follow-up and flare-visits.
Between-group difference in PROM
Medication adherence is measured by the Medical Adherence Rating Scale (MARS), where the minimum value is 5 and the maximum value is 25, meaning lower scores indicate a better outcome of higher medication adherence. This scale is administered at baseline, 3, 6, 12, 18, and 24 months, as well as at flare visits.
Measured: At baseline and 3, 6, 12, 18 and 24 months of follow-up and flare-visits.
Between-group difference in PROM
Disease impact is additionally measured by the Transition Scale, where the minimum value is -3 (representing Much worse) and the maximum value is +3 (representing Much better), meaning higher scores indicate a better outcome of subjective improvement in health status compared to baseline. This scale is administered at baseline, 3, 6, 12, 18, and 24 months, as well as at flare visits.
Measured: At baseline and 3, 6, 12, 18 and 24 months of follow-up and flare-visits.
Between-group difference in radiographic progression
Radiographic joint damage is measured by the change between baseline and 24 months in the Simple Erosion Narrowing Score (SENS), where the minimum value is 0 and the maximum value is 86, meaning higher scores indicate a worse outcome of more severe joint destruction and progression of structural damage.
Measured: At 24 months of follow-up.
Between-group difference in physical functioning
Physical functioning is measured by the Health Assessment Questionnaire-Disability Index (HAQ-DI), where the minimum value is 0 and the maximum value is 3, meaning higher scores indicate a worse outcome of greater functional disability and impairment. This questionnaire is administered at baseline, 3, 6, 12, 18, and 24 months, as well as at flare visits.
Measured: At baseline and 3, 6, 12, 18 and 24 months of follow-up and flare-visits.
Between-group difference in quality of life
Health-related quality of life is measured by the Euro Quality of Life 5-Dimensions 5-Levels (EQ-5D-5L) questionnaire, where the minimum value is 0 or 1 (0 for the visual analogue scale and 5 for the level sum scores) and the maximum value is 5 or 100 (5 for the level sum scores and 100 for the visual analogue scale), meaning higher scores indicate a worse outcome of better overall health status. This questionnaire is administered at baseline, 3, 6, 12, 18, and 24 months, as well as at flare visits.
Measured: At baseline and 3, 6, 12, 18 and 24 months of follow-up and flare-visits.
Between-group difference in pharmacokinetic and immunogenicity parameters
TNFi and ADA serum levels at baseline, 3 (csDMARD discontinuation group only), and 24 months.
Measured: At baseline and 3 and 24 months of follow-up.
Between-group difference in flares
Proportion of patients relapsing/restarting combination therapy over 24 months.
Measured: At 24 months of follow-up.
Between-group difference in flares
Flare (DAS28-CRP increase from baseline of >1.2, or >0.6 if current DAS28-CRP >2.9) incidence calculated by cumulative incidence and incidence density (events per person-years) over 24 months.
Measured: At 24 months of follow-up.
Between-group difference in flares
Time-to-event analysis of first flare over 24 months.
Measured: At 24 months of follow-up.
Between-group difference in safety
Frequency and severity of adverse events (AEs) and serious adverse events (SAEs) using the Common Terminology Criteria for Adverse Events version 5 (CTCAEv5) over 24 months.
Measured: At 24 months of follow-up.
Between-group difference in medication use
Proportion of patients in the csDMARD discontinuation group using a csDMARD and/or TNFi at 24 months.
Measured: At 24 months of follow-up.
Between-group difference in medication use
Proportion of patients who have discontinued the baseline TNFi at month 24, including those who discontinue or switch to another b/tsDMARD at the 24-month visit.
Measured: At 24 months of follow-up.
Between-group difference in medication use
Dosing and route of administration of csDMARD and/or TNFi at 24 months.
Measured: At 24 months of follow-up.
Between-group difference in medication use
MTX and LEF usage characteristics, including route of administration, use and dosage of folic acid, and other RA-related comedication over 24 months.
Measured: At 24 months of follow-up.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Sep 2026
- Study start14 Jul 2026
- Primary completion1 May 2029 (estimated)
- Study completion1 May 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rheumatoid Arthritis (RA)Studies of the same condition, open and under way.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is a 24-month multicentre, randomized, controlled, open-label, non-inferiority strategy trial. A total of 202 patients with RA in sustained LDA on TNFi plus csDMARD will be randomized 2:1 (csDMARD discontinuation strategy : csDMARD continuation strategy).
- Masking
- None (open label)
- Enrolment
- 202 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sint Maartenskliniek
- Sponsor type
- University, hospital or other
- Collaborators
- ZonMw: The Netherlands Organisation for Health Research and Development
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07802678
- Sponsor's protocol ID
- 2025.36
- Other IDs
- 2026-525316-33-00, 2025.36
- Acronym
- DISCO
- Status last verified
- Jul 2026
- First submitted
- 4 Aug 2026
- Last updated
- 3 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Pseudonymised IPD will be shared after publication of the primary results under controlled access upon reasonable request and after approval of a research proposal and data use agreement.
Study at a glance
From the registry record, last updated by the sponsor on 3 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- DISCO: DIScontinuation of COncomitant Disease Modifying Anti-rheumatic Drugs (DMARDs) in Rheumatoid Arthritis Patients Also Using TNF Inhibitors - a Randomized Long-term Non-inferiority Strategy Trial
- ClinicalTrials.gov ID
- NCT07802678
- Acronym / sponsor ID
- DISCO / 2025.36
- Conditions
- Rheumatoid Arthritis (RA)
- Keywords
- TNF inhibitors, csDMARDs, Disease activity, Mean-time weighted
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 202 participants (estimated)
- Lead sponsor
- Sint MaartenskliniekUniversity, hospital or other
- Collaborators
- ZonMw: The Netherlands Organisation for Health Research and Development
- Study start
- 14 Jul 2026 (actual)
- Primary completion
- 1 May 2029 (estimated)
- Study completion
- 1 May 2029 (estimated)
- First posted
- 3 Sep 2026 (actual)
- 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.
The goal is to investigate whether a strategy of attempting to discontinue of MTX or LEF (and restart when necessary) in RA patients treated with an optimal dose (allowed dose or lower, tapered to the maximum, or according to patient preference) TNFi is not worser to a continuation of combination therapy. The study will also examine the disease-related effects of treatment that attempts to discontinue MTX or LEF, how patients experience it, its safety, and its impact on medication usage and healthcare costs.
The main outcome is the difference between treatments in average disease activity over 24 months. The study will compare whether disease activity remains similar between patients who attempt to discontinue MTX or LEF and those who continue combination therapy.
Patients will be followed for 24 months with scheduled hospital visits at baseline, after 3, 6, 12, 18, and 24 months, remote visits, and additional visits for disease flares. X-rays of the hands and feet will be taken at baseline and after 24 months. During some visits, additional blood samples will be taken to measure inflammation markers and medication levels.
Detailed description
Rationale Rheumatoid arthritis (RA) is a long-term inflammatory disease that causes joint pain, swelling, and stiffness. Many patients are treated with a combination of medications to control inflammation. These usually include a biological medicine called a TNF inhibitor (TNFi) and another medicine, methotrexate (MTX) or leflunomide (LEF). Although this combination treatment is effective, patients often experience side effects (such as gastro-intestinal complaints and fatigue), require frequent blood tests, and may experience treatment fatigue from taking multiple medications. Patients would therefore prefer to reduce their medication. The safe reduction of TNFi treatment has been studied before. It is still unclear whether patients can safely discontinue MTX or LEF when their disease is well controlled. This study investigates whether attempting to discontinue MTX or LEF while using a TNF inhibitor is no worse than continuing combination treatment in terms of disease activity, with the hope of reducing side effects, the need for monitoring, and healthcare costs.
Objective The objective is to investigate whether a strategy of attempting to discontinue of MTX or LEF (and restart when necessary) in RA patients treated with an optimal dose (allowed dose or lower, tapered to the maximum, or according to patient preference) TNFi is not worser to a continuation of combination therapy. The study will also examine the disease-related effects of treatment that attempts to discontinue MTX or LEF, how patients experience it, its safety, and its impact on medication usage and healthcare costs.
Main trial endpoints The main endpoint is the difference between treatments in average disease activity over 24 months. The study will compare whether disease activity remains similar between patients who attempt to discontinue MTX or LEF and those who continue combination therapy.
Secondary trial endpoints Other study outcomes include the proportion of patients in the discontinuation strategy group using MTX/LEF and/or a TNFi after 24 months, and differences between treatments in patient-reported outcomes, joint damage measured by X-ray, blood levels of TNF inhibitors, safety and cost-effectiveness.
Trial design This study is being conducted in multiple hospitals. A total of 202 patients with RA will be randomly assigned to stopping MTX/LEF or continuation of combination therapy and followed for 24 months. Two-thirds of the patients will attempt to discontinue MTX or LEF (discontinuation group), and one-third will continue using the combination treatment (continuation group).
Trial population Adult patients aged 18 years and older with RA are eligible to participate if their disease has low disease activity for at least six months during treatment with a TNFi in combination with MTX or LEF.
Interventions In this study, we examine the difference between two groups: the discontinuation group and the continuation group. In the discontinuation group, patients immediately stop taking MTX or LEF and use only the TNFi at a stable dose. When disease activity increases, MTX or LEF can be restarted at the previous dose. If necessary, temporary treatment, such as glucocorticoids, can be administered. In the continuation group, patients continue using combination therapy with MTX or LEF and a TNFi at stable doses. In both groups, the goal is to maintain a stable dose of the TNFi throughout the study. Dosage adjustments or switching to a different biologic drug are permitted if disease activity increases or if side effects occur. These decisions are made by the treating rheumatologist in consultation with the patient.
During the 24-month study, patients continue to receive regular care, including six-monthly check-ups and laboratory tests. An additional study visit takes place after 3 months to detect changes in disease activity at an early stage. In addition, remote visits (by telephone) will take place at 9, 15 and 21 months. Additional visits can be scheduled if a disease flare is suspected.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- This is a 24-month multicentre, randomized, controlled, open-label, non-inferiority strategy trial. A total of 202 patients with RA in sustained LDA on TNFi plus csDMARD will be randomized 2:1 (csDMARD discontinuation strategy : csDMARD continuation strategy).
| Arm | Type | Receives |
|---|---|---|
| csDMARD discontinuation | Experimental | Drug: Strategy to attempt discontinuation of MTX or LEF (and restart when necessary)Participants will discontinue their csDMARD (MTX or LEF) immediately following randomization and continue TNFi monotherapy at their current stable dose. |
| csDMARD continuation | Active comparator | Drug: Continuation of MTX or LEFParticipants will aim to continue combination therapy with csDMARD (MTX or LEF) and TNFi at their current stable doses. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Age ≥ 18 years.
- Diagnosis of RA, according to the 2010 ACR/EULAR and/or 1987 RA classification criteria or clinical diagnosis by a rheumatologist.
- Stable disease activity for ≥ 6 months, defined as DAS28-CRP ≤ 2.9 or DAS28-CRP ≤ 3.5 combined with clinical judgment of LDA.
- Current combination therapy consisting of TNFi and either MTX or LEF.
- TNFi administration at a stable dose (at an optimal dose, defined as the authorized dose or lower and being maximally tapered, because of prior disease flare or patient preference) for ≥6 months prior to screening, during which LDA is maintained for ≥6 months.
Key exclusion criteria (7 listed)
- A previous attempt within the last 12 months prior to screening to taper or discontinue MTX or LEF that required reintroduction or dose increase of the csDMARD due to a disease flare.
- Current MTX or LEF treatment for other indications than RA.
- Current treatment with prednisolone (equivalent) of > 5 mg per day.
- Current severe comorbidity or serious life-shortening condition that could interfere with adherence to the study protocol or completion of the 24-month follow-up period.
- Women that are pregnant, breast feeding or considering pregnancy during the study period (MTX and LEF are contraindicated in pregnancy and breastfeeding).
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 |
|---|---|---|
| Strategy to attempt discontinuation of MTX or LEF (and restart when necessary)Participants will discontinue their csDMARD (MTX or LEF) immediately following randomization and continue TNFi monotherapy at their current stable dose. | Drug | csDMARD discontinuation |
| Continuation of MTX or LEFParticipants will aim to continue combination therapy with csDMARD (MTX or LEF) and TNFi at their current stable doses. | Drug | csDMARD continuation |
Primary outcome
The between-group difference in mean time-weighted DAS28-CRP during 24 months of follow-up.
Time frame: At 24 months of follow-up.
The between-group difference in mean time-weighted DAS28-CRP during 24 months of follow-up. A mean time-weighted DAS28-CRP is chosen to balance the limitations of assessing disease activity at a single timepoint with solely considering the occurrence of flare. The time-weighted DAS28-CRP consists of a weighted average of a patient's DAS28-CRP scores, calculated using the trapezoid method and weighed by the time interval between measurements.
20 secondary outcomes
Between-group difference in disease activity
Time frame: At 3, 6, 12, 18 and 24 months of follow-up.
Between-group difference at specific timepoint disease activity
Time frame: At 3, 6, 12, 18 and 24 months of follow-up.
Between-group difference in PROM
Time frame: At baseline and 3, 6, 12, 18 and 24 months of follow-up and flare-visits.
Between-group difference in PROM
Time frame: At baseline and 3, 6, 12, 18 and 24 months of follow-up and flare-visits.
Between-group difference in PROM
Time frame: At baseline and 3, 6, 12, 18 and 24 months of follow-up and flare-visits.
Between-group difference in PROM
Time frame: At baseline and 3, 6, 12, 18 and 24 months of follow-up and flare-visits.
Between-group difference in PROM
Time frame: At baseline and 3, 6, 12, 18 and 24 months of follow-up and flare-visits.
Between-group difference in PROM
Time frame: At baseline and 3, 6, 12, 18 and 24 months of follow-up and flare-visits.
Between-group difference in radiographic progression
Time frame: At 24 months of follow-up.
Between-group difference in physical functioning
Time frame: At baseline and 3, 6, 12, 18 and 24 months of follow-up and flare-visits.
Between-group difference in quality of life
Time frame: At baseline and 3, 6, 12, 18 and 24 months of follow-up and flare-visits.
Between-group difference in pharmacokinetic and immunogenicity parameters
Time frame: At baseline and 3 and 24 months of follow-up.
Between-group difference in flares
Time frame: At 24 months of follow-up.
Between-group difference in flares
Time frame: At 24 months of follow-up.
Between-group difference in flares
Time frame: At 24 months of follow-up.
Between-group difference in safety
Time frame: At 24 months of follow-up.
Between-group difference in medication use
Time frame: At 24 months of follow-up.
Between-group difference in medication use
Time frame: At 24 months of follow-up.
Between-group difference in medication use
Time frame: At 24 months of follow-up.
Between-group difference in medication use
Time frame: At 24 months of follow-up.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Sep 2026.
- Individual participant dataSharing planned: Yes. Pseudonymised IPD will be shared after publication of the primary results under controlled access upon reasonable request and after approval of a research proposal and data use agreement.
Related trials for Rheumatoid Arthritis (RA)
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
Active, not recruitingObservational study
Overactive Bladder Symptoms and Urinary Incontinence In Women With Rheumatoid Arthritis
Rheumatoid Arthritis, Rheumatoid Arthritis (RA)
Recruiting
GenAI-Assisted Rheumatoid Arthritis Bone Erosion Risk Assessment and DMARD Selection
Rheumatoid Arthritis
Not yet recruitingObservational study
The Impact of Rheumatoid Arthritis Treatments on the Modulation of Extracellular Vesicles and Other Biomarkers Involved in the Development of Lung Cancer
Rheumatoid Arthritis (RA), Lung Neoplasms
Not yet recruiting
MYTP01 for Immune-Mediated Diseases
IgA Nephropathy, Kidney Transplant Recipients
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.
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Strategy to attempt discontinuation of MTX or LEF (and restart when necessary) and Continuation of MTX or LEF in people with Rheumatoid Arthritis (RA), run by Sint Maartenskliniek at 4 sites in Netherlands.
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 8 inclusion and 7 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: looking for participants now, as of the sponsor's last update on 3 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Netherlands. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Alfons den Broeder, Dr. (++ 31 24 365 9279, a.denbroeder@maartenskliniek.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The between-group difference in mean time-weighted DAS28-CRP during 24 months of follow-up. (time frame: At 24 months of follow-up.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 3 Sep 2026.