TrEatment Targets in Rheumatoid Arthritis: TETRA-study (TETRA)

TrEatment Targets in Rheumatoid Arthritis: a Randomized Multi-centre, Treat to Target Strategy Trial: TETRA Study

There is currently no cure for rheumatoid arthritis (RA), but many treatment options are available. The central aim of RA treatment is lowering disease activity. The proactive treatment strategy called treat to target (T2T) includes measuring disease activity, setting a target and adjusting treatment accordingly until the goal is reached. T2T has proven to be superior to usual care, but there is much debate regarding the most optimal treatment measure and target. The Disease Activity Score with 28-joint counts and c-reactive protein (DAS28CRP) low-disease activity (LDA) target and the more stringent Simplified Disease Activity Index (SDAI) remission target are the best validated targets. Especially the DAS28CRP is the most commonly used in research and practice, whereas the SDAI remission target is most recommended. The European Alliance of Associations for Rheumatology (EULAR) recommends to strive for remission, whereas the American College of Rheumatology (ACR) recommends to strive for LDA. In patients with new and established RA, the (cost)effectiveness of aiming for remission compared to LDA when starting and tapering antirheumatic drugs has not been directly compared. This study therefore aims to directly compare two T2T strategies, aiming at DAS28CRP-LDA and SDAI remission, in patients with established RA.

Study Overview

• Status: Active, not recruiting
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Other: Treatment target DAS28CRP-LDA; Other: Treatment target SDAI-remission

• Study Type: Interventional
• Enrollment (Estimated): 340
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Ubbergen, Netherlands, 6574 NA
    • Sint Maartenskliniek

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of RA (according to the 2010 or 1987 ACR/ EULAR classification criteria and/or clinical diagnosis)
• (Starting) use of a DMARD
• Aged 16 years or older
• At most low disease activity, operationalised as DAS28-CRP <3.5 (DAS28 CRP 2.9 cut off for low disease activity with measurement error 0.6) or SDAI <19 (SDAI 11 cut off for low disease activity with measurement error of 8). A state of low disease activity is required at inclusion, as for RA patients in moderate or high disease activity there is no equipoise on the best course of action (treatment needs to be escalated).
• Fluency of Dutch or English, both written and verbally; able to fill in questionnaires
• Provided informed consent

Exclusion Criteria:

• Clinical deep remission, operationalised as SDAI <3.3 or DAS28-CRP <2.4, and an taper attempt in the past 2 years that was discontinued due to occurrence of flare.
• Fewer than 3 DMARD treatment options left for this patient (severe difficult-to-treat or refractory RA)
• Current severe comorbidity or other serious life-shortening conditions hampering trial participation
• Inability to comply with the study protocol or to provide informed consent with regard to intervention control and measuring outcomes

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DAS28CRP-LDA; Arm that is allocated to strive for DAS28CRP low disease activity (LDA)	Other: Treatment target DAS28CRP-LDA; Aiming for DAS28CRP-low disease activity
Experimental: SDAI-remission; Arm that is allocated to strive for SDAI-remission	Other: Treatment target SDAI-remission; Aiming for SDAI-remission

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Achievement of the composite clinical/radiological remission outcome	Achievement of the composite clinical/radiological remission outcome (radiographic progression ≤1 simple erosion narrowing score (SENS), AND, ≤1 swollen joint count, and being in PASS) at 18 months.	18 months follow-up time point

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of patients having radiographic progression (defined as > 1 simple erosion narrowing score (SENS) point) in both treatment arms		18 months follow-up
The number of swollen joints at 18 months follow-up		18 months follow-up
The proportion of patients achieving 'patient acceptable symptom state' (PASS)		18 months follow-up
The proportion of patients who reach the predefined target for each treatment arm (DAS28CRP-LDA or SDAI remission)		18 months follow-up
Percentage of patients that reach LDA or remission, using DAS28CRP- and SDAI-based definitions, in each treatment arm		18 months follow-up
Daily functioning, measured by the Health Assessment Questionnaire-Disability Index (HAQ-DI)	The Health Assessment Questionnaire-Disability Index (HAQ-DI) will be used to measure the impact of the rheumatoid arthritis on daily functioning. A minimum score of 0 and a maximum score of 60 can be scored. A higher score means a higher impact on daily functioning.	18 months follow-up
Quality of life (QoL) as defined by the 'EuroQol 5 Dimensions with 5 levels' (EQ5D-5L) questionnaire	This questionnaire assesses five dimensions of health, including mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension can be answered on a 5-point scale, ranging from no problems to extreme problems/unable to. A higher score means a worse outcome.	18 months follow-up
Incidence density rates of safety ((serious) adverse events, according to CTCAE criteria version 5.0)		18 months follow-up
Drug use of the patients, consisting of the type and volume of antirheumatic drugs (glucocorticoids, DMARDS, NSAIDs) used over the 18 months period, and at 18 months visit		18 months follow-up
Costs associated with medical consumption as assessed with the 'Institute for Medical Technology Assessment Medical Consumption Questionnaire' (iMCQ)		18 months follow-up
Costs associated with loss of productivity as measured bij the 'Institute of Medical Technology Assessment Productivity Cost Questionnaire (iMTA PCQ)	This is a short generic questionnaire that measures loss of productivity (e.g., both paid and unpaid work) due to illness or recovery.	18 months follow-up
Proportion of patients of whom the rheumatologist adhered to the local guidelines to treat the patients	Clinicians are encouraged to adhere to protocol upfront, and adherence is actively monitored, but treatment decisions are ultimately made using shared decision making between patients and physicians. After study completion, adherence will be assessed through a comparison of the target measurements and any changes in treatment regime made by the rheumatologists.	18 months follow-up
The incidence density rate of flares		18 months follow-up

Collaborators and Investigators

• Sponsor: Sint Maartenskliniek
• Investigators: Principal Investigator: Alfons Den Broeder, MD, PhD, Sint Maartenskliniek

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2023
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2027

Study Registration Dates

• First Submitted: August 15, 2023
• First Submitted That Met QC Criteria: September 13, 2023
• First Posted (Actual): September 21, 2023

Study Record Updates

• Last Update Posted (Estimated): September 11, 2025
• Last Update Submitted That Met QC Criteria: September 4, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Skin and Connective Tissue Diseases; Arthritis, Rheumatoid
• Other Study ID Numbers: TETRA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No