Skip to main content
OpenTrials
Completed

NCT Number: NCT01881308

Assessing Withdrawal of Disease-Modifying Antirheumatic Drugs in Rheumatoid Arthritis

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

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

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Department of Rheumatology, Haukeland University Hospital, Helse Bergen HF, Bergen, Norway

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

TNF inhibitors

Drug

Synthetic DMARD(s)

Drug

Co-medication: Synthetic DMARDs

Drug

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

Primary outcomes

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

    Time frame: 12 months

    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.

Secondary outcomes

  1. Disease Activity Score (DAS)

    Time frame: 12 months, with subsequent long-term analyses after 24 months and 36 months

    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

  2. Disease Activity Score in 28 joints (DAS28)

    Time frame: 12 months, with subsequent long-term analyses after 24 months and 36 months

    The 28-joint Disease Activity Score (DAS28) includes the 28- tender joint counts (TJC28), 28-swollen joint counts (SJC28), Erythrocyte Sedimentation Rate (ESR) and Patient Global Assessment (PGA) on a VAS.

  3. Simplified Disease Activity Index (SDAI)

    Time frame: 12 months, with subsequent long-term analyses after 24 months and 36 months

    SDAI includes TCJ28, SJC28, PGA, physician's global assessment of disease activity on a VAS 0-100 mm (PhGA) and C-reactive protein (CRP).

  4. Clinical Disease Activity Index (CDAI)

    Time frame: 12 months, with subsequent long-term analyses after 24 months and 36 months

    CDAI includes TCJ28, SJC28, PGA and PhGA.

  5. Swollen joint count

    Time frame: 12 months, with subsequent long-term analyses after 24 months and 36 months

    Swollen joint counts are performed on 44 joints, with total joint count ranging from 0 to 44.

  6. Tender joint count

    Time frame: 12 months, with subsequent long-term analyses after 24 months and 36 months

    Tender joints is assessed by Ritchie Articular Index which assesses tenderness of 26 joint regions, based on summation of joint responses after applying firm digital pressure. The index ranges from 0 to 3 for individual measures and the sum 0 to 78 overall.

  7. Erythrocyte Sedimentation Rate (ESR)

    Time frame: 12 months, with subsequent long-term analyses after 24 months and 36 months

    Assessment of ESR in mm/h

  8. C-reactive protein (CRP)

    Time frame: 12 months, with subsequent long-term analyses after 24 months and 36 months

    Assessment of CRP in mg/L

  9. Patient's assessment of disease activity (PGA)

    Time frame: 12 months, with subsequent long-term analyses after 24 months and 36 months

    PGA is the patient's assessment of disease activity on a VAS 0-100 mm.

  10. Physician's global assessment of disease avtivity (PHGA)

    Time frame: 12 months, with subsequent long-term analyses after 24 months and 36 months

    PHGA is the investigator's assessment of disease activity on a VAS 0-100 mm.

  11. Health Assessment Questionnaire (HAQ-PROMIS)

    Time frame: 12 months, with subsequent long-term analyses after 24 months and 36 months

    The HAQ-PROMIS is a questionnaire evaluating the physical function in patients with RA.

  12. EuroQol-5 Dimension (EQ-5D)

    Time frame: 12 months, with subsequent long-term analyses after 24 months and 36 months

    EQ-5D is a standardised instrument for use as a measure of health outcome.

  13. Medical Outcomes Study Short-Form 36-item (SF-36) Physical and Mental Component Summary Score

    Time frame: 12 months, with subsequent long-term analyses after 24 months and 36 months

    The SF-36 is a multi-purpose, short-form health survey with only 36 questions. It yields an 8-scale profile of functional health and well-being scores as well as psychometrically-based physical and mental health summary measures and a preference-based health utility index.

  14. Work performance

    Time frame: 12 months, with subsequent long-term analyses after 24 months and 36 months

    • Absenteeism (work time missed)
    • Presenteeism (impairment at work / reduced on-the-job effectiveness)
    • Work productivity loss (overall work impairment / absenteeism plus presenteeism)
    • Activity Impairment

  15. Radiographic joint damage

    Time frame: 12 months, with subsequent long-term analyses after 24 months and 36 months

    Radiographs of hands (posterior/anterior) and foot (anterior/posterior) will be taken at baseline, 12, 24 and 36 months. The modified Sharp van der Heijde Score (vdHSS) will be calculated, including an erosion score and a joint space narrowing score.

  16. Ultrasonography (subclinical synovitis)

    Time frame: 12 months, with subsequent long-term analyses after 24 months and 36 months

    36 joints and 2 tendons will be scored for both grey scale and power doppler synovitis on a 0-3 scale.

  17. DAS-remission

    Time frame: 12 months, with subsequent long-term analyses after 24 months and 36 months

    Remission is defined as a DAS-score <1.6

  18. DAS28-remission

    Time frame: 12 months, with subsequent long-term analyses after 24 months and 36 months

    Remission is defined as a DAS28 score < 2.6

  19. SDAI-remission

    Time frame: 12 months, with subsequent long-term analyses after 24 months and 36 months

    Remission is defined as a SDAI score ≤ 3.3

  20. CDAI-remission

    Time frame: 12 months, with subsequent long-term analyses after 24 months and 36 months

    Remission is defined as a CDAI score ≤ 2.8

  21. ACR/EULAR Boolean remission

    Time frame: 12 months, with subsequent long-term analyses after 24 months and 36 months

    The patient must satisfy all of the following in order to achieve ACR/EULAR remission:

    • RAI ≤ 1
    • SJC44 ≤ 1
    • CRP ≤ 1
    • PGA ≤ 1 (on a scale 0-10, in this study ≤ 14 on a scale 0-100)

  22. No swollen joint

    Time frame: 12 months, with subsequent long-term analyses after 24 months and 36 months

    The percentage of patients with no swollen joints will be assessed

  23. Radiographic outcome

    Time frame: 12 months, with subsequent long-term analyses after 24 months and 36 months

    No radiographic progression

  24. Ultrasound outcome

    Time frame: 12 months, with subsequent long-term analyses after 24 months and 36 months

    No ultrasound power Doppler signal in any joint.

  25. American College of Rheumatology (ACR) response

    Time frame: 12 months, with subsequent long-term analyses after 24 months and 36 months

    If a patient has experienced a flare, and treatment has been escalated, the ACR 2050/70/90 response will be calculated.

  26. The European League Against Rheumatism (EULAR) response

    Time frame: 12 months, with subsequent long-term analyses after 24 months and 36 months

    If a patient has experienced a flare, and treatment has been escalated, the EULAR response will be calculated.

  27. The Food and Drug Administration (FDA) major clinical response

    Time frame: 12 months, with subsequent long-term analyses after 24 months and 36 months

    If a patient has experienced a flare, and treatment has been escalated, the FDA major clinical response will be calculated.

  28. Medication

    Time frame: 12 months, with subsequent long-term analyses after 24 months and 36 months

    The number of patients on different conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and biologic therapy. Dose of DMARDs in users will be recorded, prednisolone usages and number of intraarticular injections.

Sponsors and collaborators

Lead sponsor

Diakonhjemmet Hospital

Other

Collaborators

  • South-Eastern Norway Regional Health Authority
  • The Research Council of Norway

Registry information

Official study title

REmission in Rheumatoid Arthritis - Assessing WIthrawal of Disease-modifying Antirheumatic Drugs in a Non-inferiority Design

Acronym: ARCTIC REWIND

Important dates

Study start
2013
Primary completion
2020
Study completion
2022
First posted
Jun 19, 2013
Registry last updated
Apr 26, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.