Assessing Withdrawal of Disease-Modifying Antirheumatic Drugs in Rheumatoid Arthritis (ARCTIC REWIND)

Diakonhjemmet Hospital

Status and phase: Completed; Phase 4

Conditions: Rheumatoid Arthritis

Treatments: Drug: Synthetic DMARD(s); Drug: Co-medication: Synthetic DMARDs; Drug: TNF inhibitors

Study type: Interventional

Funder types: Other

Identifiers

NCT01881308

DIA2012-1/ver4_1

2012-005275-14 (EudraCT Number)

Details and patient eligibility

About

The purpose of this study is to assess the effect of disease-modifying anti-rheumatic drugs (DMARDs) dose reduction in patients with rheumatoid arthritis (RA).

Remission is the treatment target in RA, but knowledge about the best way to treat RA patients who achieve sustained remission is limited. DMARDs have potential serious adverse events, and biologic DMARDs are costly to the society. The objectives for ARCTIC REWIND are to assess the effect of tapering and withdrawal of DMARDs on disease activity in RA patients in sustained remission, to study predictors for successful tapering and withdrawal of DMARDs in this patient group, and to study cost-effectiveness of different treatment options in RA remission.

ARCTIC REWIND is a randomized, open, controlled, parallel-group, multicenter, phase IV, non-inferiority strategy study. Patients with less than five years of disease duration and stable remission for at least 12 months are randomized to either continued stable treatment or tapering and withdrawal of DMARDs, including tumor necrosis factor (TNF) inhibitors and synthetic DMARDs. Patients are assessed by clinical examination, patient reported outcome measures, ultrasonography, MRI and X-ray, and monitored for adverse events. The primary endpoint of the study is the proportion of patients who are non-failures (have not experienced a flare) at 12 months. Secondary endpoints include composite disease activity scores and remission criteria, joint damage and inflammation assessed by various imaging modalities, work participation, health care resource use and health related quality of life.

Enrollment: 320 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Rheumatoid arthritis according to the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria
• Male or non-pregnant, non-nursing female
• >18 years of age and <80 years of age
• Patient in the TNF-inhibitor group: Any disease duration. Patient in the synthetic DMARD group: RA diagnosis after 01.01.2010.
• Sustained remission for ≥12 months according to DAS or Disease Activity Score based on 28 joints (DAS28), with documented remission status at a minimum of 2 consecutive visits during the last 18 months OR participation in the first ARCTIC trial
• DAS <1.6 and no swollen joints at inclusion OR participation in the first ARCTIC trial
• Unchanged treatment with TNF inhibitors and/or synthetic DMARDs during the previous 12 months, with a stable or reduced dose of glucocorticosteroids OR participation in the first ARCTIC trial
• Subject capable of understanding and signing an informed consent form
• Provision of written informed consent

Exclusion criteria

• Abnormal renal function, defined as serum creatinine >142 μmol/L in female and >168 μmol/L in male, or a glomerular filtration rate (GFR) <40 mL/min/1.73 m2
• Abnormal liver function (defined as aspartate transaminase (ASAT)/alanine aminotransferase (ALAT) >3x upper normal limit), active or recent hepatitis, cirrhosis
• Major co-morbidities, such as severe malignancies, severe diabetic mellitus, severe infections, uncontrollable hypertension, severe cardiovascular disease (NYHA class 3 or 4) and/or severe respiratory diseases
• Leukopenia and/or thrombocytopenia
• Inadequate birth control, pregnancy, and/or breastfeeding
• Indications of active tuberculosis
• Psychiatric or mental disorders, alcohol abuse or other substance abuse, language barriers or other factors which makes adherence to the study protocol impossible.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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320 participants in 5 patient groups

Stable dose TNF inhibitor

Active Comparator group

Description:

Stable dose TNF inhibitor. Any co-medication with synthetic DMARDs kept stable.

Treatment:

Drug: TNF inhibitors

Drug: Co-medication: Synthetic DMARDs

Stepdown and withdrawal of TNF inhibitor

Experimental group

Description:

Half-dose of TNF inhibitor for the first four months, thereafter withdrawal of TNF inhibitor. Any co-medication with synthetic DMARDs kept stable.

Treatment:

Drug: TNF inhibitors

Drug: Co-medication: Synthetic DMARDs

Stable dose synthetic DMARD

Active Comparator group

Description:

Stable dose of synthetic DMARDs, either monotherapy or combination therapy.

Treatment:

Drug: Synthetic DMARD(s)

Synthetic DMARD dose reduction

Experimental group

Description:

Half-dose synthetic DMARDs (monotherapy or combination therapy) for the first 12 months of the study. Patients classified as non-failures are re-randomized at 12 months to either continue half-dose synthetic DMARD(s) or withdraw all DMARD(s).

Treatment:

Drug: Synthetic DMARD(s)

ARCTIC follow-up

Other group

Description:

Patients are treated according to the ARCTIC treatment schedule based on disease activity.

Treatment:

Drug: Synthetic DMARD(s)

Drug: TNF inhibitors

Drug: Co-medication: Synthetic DMARDs