Assessing Withdrawal of Disease-Modifying Antirheumatic Drugs in Rheumatoid Arthritis

Diakonhjemmet Hospital320 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

320

Conditions

Interventions

TNF inhibitorsDRUG

Synthetic DMARD(s)DRUG

Co-medication: Synthetic DMARDsDRUG

Synthetic DMARDs given as co-medication for TNF inhibitors as appropriate.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

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.

Locations (10)

Department of Rheumatology, Helse Møre og Romsdal HF

Ålesund, Norway

Department of Rheumatology, Haukeland University Hospital, Helse Bergen HF

Bergen, Norway

Department of Rheumatology, Drammen Hospital, Vestre Viken HF

Drammen, Norway

Department of Rheumatology, Sykehuset Østfold HF

Fredrikstad, Norway

Department of Rheumatology, Sørlandet Sykehus HF

Kristiansand, Norway

Revmatismesykehuset AS

Lillehammer, Norway

Helgelandssykehuset, Mo i Rana

Mo i Rana, Norway

Department of Rheumatology, Diakonhjemmet Hospital

Oslo, Norway

Martina Hansens Hospital AS

Sandvika, Norway

Universitetssykehuset Nord-Norge HF

Tromsø, Norway

Outcomes

Primary Outcomes

Proportion of patients who are non-failures (have not experienced a flare)

Flare is defined as composite measure: (1) An increase in disease activity score (DAS) to \>1.6 AND (2) a change in DAS of at least 0.6 AND (3) \> 1 swollen joint. If a patient does not fulfill this formal definition, but experiences a clinically significant flare according to the investigator and patient, this is treated as a flare.

Time frame: 12 months

Secondary Outcomes

Disease Activity Score (DAS)

The DAS is a composite score that includes the Ritchie articular index (RAI), the 44- swollen joint counts (SJC-44), the Erythrocyte Sedimentation Rate (ESR) and a general health (GH) assessment on a Visual Analogue Scale (VAS). The DAS is calculated as follows: DAS = 0.54\*sqrt(RAI) + 0.065\*(SJC-44) + 0.33\*Ln(ESR) + 0.0072\*GH