Discontinuation of Disease-modifying Anti-rheumatic Drugs (DMARDs) in Rheumatoid Arthritis Patients Also Using TNF Inhibitors

NCT07802678 | Recruiting Phase 4 DMC

• 2 other identifiers: 2025.362026-525316-33-00
• Study Type: interventional
• Target: 202
• Locations: 1 country
• Sites: 4

Brief 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. 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.

Conditions

Rheumatoid Arthritis (RA)

Keywords

TNF inhibitors; csDMARDs; Disease activity; Mean-time weighted

Outcome Measures

Primary Outcomes (1)

• 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.

  At 24 months of follow-up.

Secondary Outcomes (20)

• Between-group difference in disease activity

  At 3, 6, 12, 18 and 24 months of follow-up.

• Between-group difference at specific timepoint disease activity

  At 3, 6, 12, 18 and 24 months of follow-up.

• Between-group difference in PROM

  At baseline and 3, 6, 12, 18 and 24 months of follow-up and flare-visits.

• Between-group difference in PROM

  At baseline and 3, 6, 12, 18 and 24 months of follow-up and flare-visits.

• Between-group difference in PROM

  At baseline and 3, 6, 12, 18 and 24 months of follow-up and flare-visits.

Other Outcomes (3)

• Cost-effectiveness

  At baseline and 3, 16, 12, 18 and 24 months of follow-up.

• Cost-effectiveness

  At baseline and 3, 16, 12, 18 and 24 months of follow-up.

• Predictors of successful csDMARD discontinuation

  At 24 months of follow-up.

Study Arms (2)

csDMARD discontinuation

EXPERIMENTAL

Participants will discontinue their csDMARD (MTX or LEF) immediately following randomization and continue TNFi monotherapy at their current stable dose.

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.

Drug: Continuation of MTX or LEF

Interventions

Continuation of MTX or LEF DRUG

Participants will aim to continue combination therapy with csDMARD (MTX or LEF) and TNFi at their current stable doses.

csDMARD continuation

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.

csDMARD discontinuation

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sint Maartenskliniek: lead
• ZonMw: The Netherlands Organisation for Health Research and Development: collaborator

Study Sites (4)

Sint Maartenskliniek

Nijmegen, Gelderland, 6574NA, Netherlands

RECRUITING

Elisabeth-TweeSteden Ziekenhuis Tilburg

Tilburg, North Brabant, 5022 GC, Netherlands

NOT YET RECRUITING

Reade Amsterdam

Amsterdam, North Holland, 1056 AA, Netherlands

NOT YET RECRUITING

Erasmus MC

Rotterdam, South Holland, 3015GJ, Netherlands

NOT YET RECRUITING

MeSH Terms

Conditions

Arthritis, Rheumatoid

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Alfons den Broeder, Dr.

CONTACT

++ 31 24 365 9279; a.denbroeder@maartenskliniek.nl

Sophie Marie Gerritsen, MSc.

CONTACT

++ 316 49 67 69 86; so.gerritsen@maartenskliniek.nl

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: August 4, 2026
• First Posted: September 3, 2026
• Study Start: July 14, 2026
• Primary Completion (Estimated): May 1, 2029
• Study Completion (Estimated): May 1, 2029
• Last Updated: September 3, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share

Locations

NL (4)