Rheumatoid ArthritisPhase 4ARCTIC REWINDNCT01881308
Assessing Withdrawal of Disease-Modifying Antirheumatic Drugs in Rheumatoid Arthritis
A Phase 4 study testing TNF inhibitors, Synthetic DMARD(s) and Co-medication: Synthetic DMARDs in people with Rheumatoid Arthritis, run by Diakonhjemmet Hospital at 10 sites in Norway.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- TNF inhibitors, Synthetic DMARD(s) and Co-medication: Synthetic DMARDs
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 320 participants
- Where
- 10 sitesNorway
- Study dates
- 17 Jun 2013to Jan 2022
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 9Show fewer
- 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
Who cannot join
- 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 locations and contacts
10 sites in 1 country.
10 sites in 1 country
Norway10 sites
Department of Rheumatology, Helse Møre og Romsdal HF
Ålesund, 6026
Department of Rheumatology, Haukeland University Hospital, Helse Bergen HF
Bergen, 5021
Department of Rheumatology, Drammen Hospital, Vestre Viken HF
Drammen, 3004
Department of Rheumatology, Sykehuset Østfold HF
Fredrikstad, 1603
Department of Rheumatology, Sørlandet Sykehus HF
Kristiansand, 4604
Revmatismesykehuset AS
Lillehammer, 2609
Helgelandssykehuset, Mo i Rana
Mo i Rana, 8613
Department of Rheumatology, Diakonhjemmet Hospital
Oslo, 0319
Martina Hansens Hospital AS
Sandvika, 1306
Universitetssykehuset Nord-Norge HF
Tromsø, 9038
About this study
Official title: REmission in Rheumatoid Arthritis - Assessing WIthrawal of Disease-modifying Antirheumatic Drugs in a Non-inferiority Design
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.
- Conditions
- Rheumatoid Arthritis
- Being tested
- TNF inhibitors, Synthetic DMARD(s), Co-medication: Synthetic DMARDs
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TNF inhibitorsDrug
Synthetic DMARD(s)Drug
Co-medication: Synthetic DMARDsDrug
Synthetic DMARDs given as co-medication for TNF inhibitors as appropriate.
| Study group | Role | What they receive |
|---|---|---|
| Stable dose TNF inhibitor | Active comparator | Stable dose TNF inhibitor. Any co-medication with synthetic DMARDs kept stable. Receives: Drug: TNF inhibitors; Drug: Co-medication: Synthetic DMARDs |
| Stepdown and withdrawal of TNF inhibitor | Experimental | Half-dose of TNF inhibitor for the first four months, thereafter withdrawal of TNF inhibitor. Any co-medication with synthetic DMARDs kept stable. Receives: Drug: TNF inhibitors; Drug: Co-medication: Synthetic DMARDs |
| Stable dose synthetic DMARD | Active comparator | Stable dose of synthetic DMARDs, either monotherapy or combination therapy. Receives: Drug: Synthetic DMARD(s) |
| Synthetic DMARD dose reduction | Experimental | 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). Receives: Drug: Synthetic DMARD(s) |
| ARCTIC follow-up | Other | Patients are treated according to the ARCTIC treatment schedule based on disease activity. Receives: Drug: TNF inhibitors; Drug: Synthetic DMARD(s); Drug: Co-medication: Synthetic DMARDs |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 months
Secondary outcomes (28)
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
Measured: 12 months, with subsequent long-term analyses after 24 months and 36 months
Disease Activity Score in 28 joints (DAS28)
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.
Measured: 12 months, with subsequent long-term analyses after 24 months and 36 months
Simplified Disease Activity Index (SDAI)
SDAI includes TCJ28, SJC28, PGA, physician's global assessment of disease activity on a VAS 0-100 mm (PhGA) and C-reactive protein (CRP).
Measured: 12 months, with subsequent long-term analyses after 24 months and 36 months
Clinical Disease Activity Index (CDAI)
CDAI includes TCJ28, SJC28, PGA and PhGA.
Measured: 12 months, with subsequent long-term analyses after 24 months and 36 months
Swollen joint count
Swollen joint counts are performed on 44 joints, with total joint count ranging from 0 to 44.
Measured: 12 months, with subsequent long-term analyses after 24 months and 36 months
Tender joint count
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.
Measured: 12 months, with subsequent long-term analyses after 24 months and 36 months
Erythrocyte Sedimentation Rate (ESR)
Assessment of ESR in mm/h
Measured: 12 months, with subsequent long-term analyses after 24 months and 36 months
C-reactive protein (CRP)
Assessment of CRP in mg/L
Measured: 12 months, with subsequent long-term analyses after 24 months and 36 months
Patient's assessment of disease activity (PGA)
PGA is the patient's assessment of disease activity on a VAS 0-100 mm.
Measured: 12 months, with subsequent long-term analyses after 24 months and 36 months
Physician's global assessment of disease avtivity (PHGA)
PHGA is the investigator's assessment of disease activity on a VAS 0-100 mm.
Measured: 12 months, with subsequent long-term analyses after 24 months and 36 months
Health Assessment Questionnaire (HAQ-PROMIS)
The HAQ-PROMIS is a questionnaire evaluating the physical function in patients with RA.
Measured: 12 months, with subsequent long-term analyses after 24 months and 36 months
EuroQol-5 Dimension (EQ-5D)
EQ-5D is a standardised instrument for use as a measure of health outcome.
Measured: 12 months, with subsequent long-term analyses after 24 months and 36 months
Medical Outcomes Study Short-Form 36-item (SF-36) Physical and Mental Component Summary Score
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.
Measured: 12 months, with subsequent long-term analyses after 24 months and 36 months
Work performance
- Absenteeism (work time missed)
- Presenteeism (impairment at work / reduced on-the-job effectiveness)
- Work productivity loss (overall work impairment / absenteeism plus presenteeism)
- Activity Impairment
Measured: 12 months, with subsequent long-term analyses after 24 months and 36 months
Radiographic joint damage
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.
Measured: 12 months, with subsequent long-term analyses after 24 months and 36 months
Ultrasonography (subclinical synovitis)
36 joints and 2 tendons will be scored for both grey scale and power doppler synovitis on a 0-3 scale.
Measured: 12 months, with subsequent long-term analyses after 24 months and 36 months
DAS-remission
Remission is defined as a DAS-score <1.6
Measured: 12 months, with subsequent long-term analyses after 24 months and 36 months
DAS28-remission
Remission is defined as a DAS28 score < 2.6
Measured: 12 months, with subsequent long-term analyses after 24 months and 36 months
SDAI-remission
Remission is defined as a SDAI score ≤ 3.3
Measured: 12 months, with subsequent long-term analyses after 24 months and 36 months
CDAI-remission
Remission is defined as a CDAI score ≤ 2.8
Measured: 12 months, with subsequent long-term analyses after 24 months and 36 months
ACR/EULAR Boolean remission
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)
Measured: 12 months, with subsequent long-term analyses after 24 months and 36 months
No swollen joint
The percentage of patients with no swollen joints will be assessed
Measured: 12 months, with subsequent long-term analyses after 24 months and 36 months
Radiographic outcome
No radiographic progression
Measured: 12 months, with subsequent long-term analyses after 24 months and 36 months
Ultrasound outcome
No ultrasound power Doppler signal in any joint.
Measured: 12 months, with subsequent long-term analyses after 24 months and 36 months
American College of Rheumatology (ACR) response
If a patient has experienced a flare, and treatment has been escalated, the ACR 2050/70/90 response will be calculated.
Measured: 12 months, with subsequent long-term analyses after 24 months and 36 months
The European League Against Rheumatism (EULAR) response
If a patient has experienced a flare, and treatment has been escalated, the EULAR response will be calculated.
Measured: 12 months, with subsequent long-term analyses after 24 months and 36 months
The Food and Drug Administration (FDA) major clinical response
If a patient has experienced a flare, and treatment has been escalated, the FDA major clinical response will be calculated.
Measured: 12 months, with subsequent long-term analyses after 24 months and 36 months
Medication
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.
Measured: 12 months, with subsequent long-term analyses after 24 months and 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jun 2013 (estimated)
- Study start17 Jun 2013
- Primary completionJan 2020
- Study completionJan 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 320 participants (actual)
Sponsor and investigators
- Lead sponsor
- Diakonhjemmet Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- The Research Council of Norway, South-Eastern Norway Regional Health Authority
- Responsible party
- Principal investigator, Espen A. Haavardsholm, MD PhD, Diakonhjemmet Hospital
- Investigators
- Espen A. Haavardsholm, MD PhD, Principal investigator, Diakonhjemmet HospitalTore K Kvien, MD PhD, Study director, Diakonhjemmet Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01881308
- Sponsor's protocol ID
- DIA2012-1/ver4_1
- Other IDs
- 2012-005275-14
- Acronym
- ARCTIC REWIND
- Status last verified
- Apr 2022
- First submitted
- 17 Jun 2013
- Last updated
- 26 Apr 2022
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes: The authors commit to making the relevant anonymized patient level data available on reasonable request.
Publications
Kjorholt KE, Sundlisaeter NP, Aga AB, Sexton J, Olsen IC, Fremstad H, Spada C, Madland TM, Hoili CA, Bakland G, Lexberg A, Hansen IJW, Hansen IM, Haukeland H, Ljosa MA, Moholt E, Uhlig T, Kvien TK, Solomon DH, van der Heijde D, Haavardsholm EA, Lillegraven S. Effects of tapering conventional synthetic disease-modifying antirheumatic drugs to drug-free remission versus stable treatment in rheumatoid arthritis (ARCTIC REWIND): 3-year results from an open-label, randomised controlled, non-inferiority trial. Lancet Rheumatol. 2024 May;6(5):e268-e278. doi: 10.1016/S2665-9913(24)00021-3. Epub 2024 Apr 4.
PubMed 38583450Holten K, Paulshus Sundlisaeter N, Sexton J, Nordberg LB, Uhlig T, Kvien TK, Solomon DH, Haavardsholm EA, Lillegraven S, Aga AB; ARCTIC REWIND study group. Performance of the Rheumatoid Arthritis Impact of Disease (RAID) score in relation to flares in disease activity. RMD Open. 2024 Jan 12;10(1):e003486. doi: 10.1136/rmdopen-2023-003486.
PubMed 38216290Lillegraven S, Paulshus Sundlisaeter N, Aga AB, Sexton J, Olsen IC, Lexberg AS, Madland TM, Fremstad H, Hoili CA, Bakland G, Spada C, Haukeland H, Hansen IM, Moholt E, Uhlig T, Solomon DH, van der Heijde D, Kvien TK, Haavardsholm EA. Effect of tapered versus stable treatment with tumour necrosis factor inhibitors on disease flares in patients with rheumatoid arthritis in remission: a randomised, open label, non-inferiority trial. Ann Rheum Dis. 2023 Nov;82(11):1394-1403. doi: 10.1136/ard-2023-224476. Epub 2023 Aug 22.
PubMed 37607809Lillegraven S, Paulshus Sundlisaeter N, Aga AB, Sexton J, Olsen IC, Fremstad H, Spada C, Madland TM, Hoili CA, Bakland G, Lexberg A, Hansen IJW, Hansen IM, Haukeland H, Ljosa MA, Moholt E, Uhlig T, Solomon DH, van der Heijde D, Kvien TK, Haavardsholm EA. Effect of Half-Dose vs Stable-Dose Conventional Synthetic Disease-Modifying Antirheumatic Drugs on Disease Flares in Patients With Rheumatoid Arthritis in Remission: The ARCTIC REWIND Randomized Clinical Trial. JAMA. 2021 May 4;325(17):1755-1764. doi: 10.1001/jama.2021.4542.
PubMed 33944875
Study at a glance
From the registry record, last updated by the sponsor on 26 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- REmission in Rheumatoid Arthritis - Assessing WIthrawal of Disease-modifying Antirheumatic Drugs in a Non-inferiority Design
- ClinicalTrials.gov ID
- NCT01881308
- Acronym / sponsor ID
- ARCTIC REWIND / DIA2012-1/ver4_1
- Conditions
- Rheumatoid Arthritis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 320 participants (actual)
- Lead sponsor
- Diakonhjemmet HospitalUniversity, hospital or other
- Collaborators
- The Research Council of Norway, South-Eastern Norway Regional Health Authority
- Study start
- 17 Jun 2013 (actual)
- Primary completion
- Jan 2020 (actual)
- Study completion
- Jan 2022 (actual)
- First posted
- 19 Jun 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Stable dose TNF inhibitor | Active comparator | Drug: TNF inhibitors, Drug: Co-medication: Synthetic DMARDsStable dose TNF inhibitor. Any co-medication with synthetic DMARDs kept stable. |
| Stepdown and withdrawal of TNF inhibitor | Experimental | Drug: TNF inhibitors, Drug: Co-medication: Synthetic DMARDsHalf-dose of TNF inhibitor for the first four months, thereafter withdrawal of TNF inhibitor. Any co-medication with synthetic DMARDs kept stable. |
| Stable dose synthetic DMARD | Active comparator | Drug: Synthetic DMARD(s)Stable dose of synthetic DMARDs, either monotherapy or combination therapy. |
| Synthetic DMARD dose reduction | Experimental | Drug: Synthetic DMARD(s)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). |
| ARCTIC follow-up | Other | Drug: TNF inhibitors, Drug: Synthetic DMARD(s), Drug: Co-medication: Synthetic DMARDsPatients are treated according to the ARCTIC treatment schedule based on disease activity. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TNF inhibitors | Drug | ARCTIC follow-up, Stable dose TNF inhibitor, Stepdown and withdrawal of TNF inhibitor |
| Synthetic DMARD(s) | Drug | ARCTIC follow-up, Stable dose synthetic DMARD, Synthetic DMARD dose reduction |
| Co-medication: Synthetic DMARDsSynthetic DMARDs given as co-medication for TNF inhibitors as appropriate. | Drug | ARCTIC follow-up, Stable dose TNF inhibitor, Stepdown and withdrawal of TNF inhibitor |
Primary outcome
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.
28 secondary outcomes
Disease Activity Score (DAS)
Time frame: 12 months, with subsequent long-term analyses after 24 months and 36 months
Disease Activity Score in 28 joints (DAS28)
Time frame: 12 months, with subsequent long-term analyses after 24 months and 36 months
Simplified Disease Activity Index (SDAI)
Time frame: 12 months, with subsequent long-term analyses after 24 months and 36 months
Clinical Disease Activity Index (CDAI)
Time frame: 12 months, with subsequent long-term analyses after 24 months and 36 months
Swollen joint count
Time frame: 12 months, with subsequent long-term analyses after 24 months and 36 months
Tender joint count
Time frame: 12 months, with subsequent long-term analyses after 24 months and 36 months
Erythrocyte Sedimentation Rate (ESR)
Time frame: 12 months, with subsequent long-term analyses after 24 months and 36 months
C-reactive protein (CRP)
Time frame: 12 months, with subsequent long-term analyses after 24 months and 36 months
Patient's assessment of disease activity (PGA)
Time frame: 12 months, with subsequent long-term analyses after 24 months and 36 months
Physician's global assessment of disease avtivity (PHGA)
Time frame: 12 months, with subsequent long-term analyses after 24 months and 36 months
Health Assessment Questionnaire (HAQ-PROMIS)
Time frame: 12 months, with subsequent long-term analyses after 24 months and 36 months
EuroQol-5 Dimension (EQ-5D)
Time frame: 12 months, with subsequent long-term analyses after 24 months and 36 months
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
Work performance
Time frame: 12 months, with subsequent long-term analyses after 24 months and 36 months
Radiographic joint damage
Time frame: 12 months, with subsequent long-term analyses after 24 months and 36 months
Ultrasonography (subclinical synovitis)
Time frame: 12 months, with subsequent long-term analyses after 24 months and 36 months
DAS-remission
Time frame: 12 months, with subsequent long-term analyses after 24 months and 36 months
DAS28-remission
Time frame: 12 months, with subsequent long-term analyses after 24 months and 36 months
SDAI-remission
Time frame: 12 months, with subsequent long-term analyses after 24 months and 36 months
CDAI-remission
Time frame: 12 months, with subsequent long-term analyses after 24 months and 36 months
ACR/EULAR Boolean remission
Time frame: 12 months, with subsequent long-term analyses after 24 months and 36 months
No swollen joint
Time frame: 12 months, with subsequent long-term analyses after 24 months and 36 months
Radiographic outcome
Time frame: 12 months, with subsequent long-term analyses after 24 months and 36 months
Ultrasound outcome
Time frame: 12 months, with subsequent long-term analyses after 24 months and 36 months
American College of Rheumatology (ACR) response
Time frame: 12 months, with subsequent long-term analyses after 24 months and 36 months
The European League Against Rheumatism (EULAR) response
Time frame: 12 months, with subsequent long-term analyses after 24 months and 36 months
The Food and Drug Administration (FDA) major clinical response
Time frame: 12 months, with subsequent long-term analyses after 24 months and 36 months
Medication
Time frame: 12 months, with subsequent long-term analyses after 24 months and 36 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Apr 2022.
- Derived from this study: PubMed 38583450Kjorholt KE, Sundlisaeter NP, Aga AB, Sexton J, Olsen IC, Fremstad H, Spada C, Madland TM, Hoili CA, Bakland G, Lexberg A, Hansen IJW, Hansen IM, Haukeland H, Ljosa MA, Moholt E, Uhlig T, Kvien TK, Solomon DH, van der Heijde D, Haavardsholm EA, Lillegraven S. Effects of tapering conventional synthetic disease-modifying antirheumatic drugs to drug-free remission versus stable treatment in rheumatoid arthritis (ARCTIC REWIND): 3-year results from an open-label, randomised controlled, non-inferiority trial. Lancet Rheumatol. 2024 May;6(5):e268-e278. doi: 10.1016/S2665-9913(24)00021-3. Epub 2024 Apr 4.
- Derived from this study: PubMed 38216290Holten K, Paulshus Sundlisaeter N, Sexton J, Nordberg LB, Uhlig T, Kvien TK, Solomon DH, Haavardsholm EA, Lillegraven S, Aga AB; ARCTIC REWIND study group. Performance of the Rheumatoid Arthritis Impact of Disease (RAID) score in relation to flares in disease activity. RMD Open. 2024 Jan 12;10(1):e003486. doi: 10.1136/rmdopen-2023-003486.
- Derived from this study: PubMed 37607809Lillegraven S, Paulshus Sundlisaeter N, Aga AB, Sexton J, Olsen IC, Lexberg AS, Madland TM, Fremstad H, Hoili CA, Bakland G, Spada C, Haukeland H, Hansen IM, Moholt E, Uhlig T, Solomon DH, van der Heijde D, Kvien TK, Haavardsholm EA. Effect of tapered versus stable treatment with tumour necrosis factor inhibitors on disease flares in patients with rheumatoid arthritis in remission: a randomised, open label, non-inferiority trial. Ann Rheum Dis. 2023 Nov;82(11):1394-1403. doi: 10.1136/ard-2023-224476. Epub 2023 Aug 22.
- Derived from this study: PubMed 33944875Lillegraven S, Paulshus Sundlisaeter N, Aga AB, Sexton J, Olsen IC, Fremstad H, Spada C, Madland TM, Hoili CA, Bakland G, Lexberg A, Hansen IJW, Hansen IM, Haukeland H, Ljosa MA, Moholt E, Uhlig T, Solomon DH, van der Heijde D, Kvien TK, Haavardsholm EA. Effect of Half-Dose vs Stable-Dose Conventional Synthetic Disease-Modifying Antirheumatic Drugs on Disease Flares in Patients With Rheumatoid Arthritis in Remission: The ARCTIC REWIND Randomized Clinical Trial. JAMA. 2021 May 4;325(17):1755-1764. doi: 10.1001/jama.2021.4542.
- Individual participant dataSharing planned: Yes. The authors commit to making the relevant anonymized patient level data available on reasonable request.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Espen A. Haavardsholm, MD PhD principal investigator
Diakonhjemmet Hospital
Tore K Kvien, MD PhD study director
Diakonhjemmet Hospital
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing TNF inhibitors, Synthetic DMARD(s) and Co-medication: Synthetic DMARDs in people with Rheumatoid Arthritis, run by Diakonhjemmet Hospital at 10 sites in Norway.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Norway. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of patients who are non-failures (have not experienced a flare) (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01881308, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Apr 2022.