Clinical trial NCT01205854: Aiming for Remission in Rheumatoid Arthritis (RA) - the ARCTIC Trial
Official title: Aiming for Remission in Rheumatoid Arthritis: a Randomized Trial Examining the Benefit of Ultrasonography in a Clinical TIght Control Regimen
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Rheumatoid Arthritis
Keywords: rheumatoid arthritis
ultrasonography
remission
imaging remission
tight control
treat to target
Lead sponsor: Diakonhjemmet Hospital
Sponsor class: OTHER
Collaborators: name: The Research Council of Norway
name: Smerud Medical Research International AS
name: Oslo University Hospital
name: Innovest
name: Abbott
name: UCB Nordic A/S
name: Pfizer
name: MSD Norway AS
name: Roche Pharma AG
name: The Norwegian Rheumatism Association
First posted: 2010-09-21
Enrollment: 238
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The ultimate goal of treatment in early rheumatoid arthritis (RA) is remission, i.e. an absence of signs and symptoms of the disease. However, the optimal way of reaching this goal is not known.

Ultrasonography (US) is an imaging modality which application is rapidly growing. It has a number of advantages over other advanced imaging techniques such as magnetic resonance imaging (MRI), including low cost, good accessibility, and ability to scan many joints in a short period of time. However, the additional benefit of using this modality in terms of patient outcomes has not been demonstrated. Thus, clarification is needed if the use of US leads to better care for RA patients.

This study will assess if the use of a treatment strategy incorporating information from ultrasonography assessment will allow for better outcomes of patients with RA, than a strategy based on clinical and laboratory assessments alone.


Eligibility criteria: Inclusion criteria (all):

* Male or non-pregnant, non-nursing female
* \> 18 years of age and \< 75 years of age
* Patients classified as having RA (according to new ACR/EULAR criteria)
* Disease duration less than 2 years (defined as time from 1st joint swelling)
* The treating rheumatologist decides the patient requires treatment with a Disease Modifying Anti-Rheumatic Drug (DMARD)
* The patient has taken no prior DMARD
* Patients able and willing to give written informed consent and comply with the requirements of the study protocol

Exclusion Criteria (any):

* Abnormal renal function (serum creatinine \> 142 µmol/L in female and \> 168 µmol/L in male)
* Abnormal liver function, active or recent hepatitis, cirrhosis
* Major co-morbidities like severe malignancies, severe diabetic mellitus, severe infections, uncontrollable hypertension, severe cardiovascular disease and/or severe respiratory diseases.
* Leukopenia and/or thrombocytopenia
* Inadequate birth control conception, pregnancy, and/or breastfeeding
* Indications of active tuberculosis
* Psychiatric or mental disorders, alcohol abuse or other abuse of substances, language barriers or other factors which makes adherence to the study protocol impossible

Primary outcomes:
measure: Complete clinical Disease Activity Score (DAS) remission
timeFrame: 24 months
Secondary outcomes:
measure: Magnetic Resonance Imaging (MRI) of dominant hand
timeFrame: 24 months
measure: American College of Rheumatology (ACR) response
timeFrame: 24 months
measure: Remission
timeFrame: 24 months
measure: European League Against Rheumatism (EULAR) response
timeFrame: 24 months
measure: Work performance
timeFrame: 24 months
measure: Conventional radiography
timeFrame: 24 months
measure: The RA Impact of Disease (RAID) score
timeFrame: 24 months
measure: EuroQol-5 Dimension (EQ-5D)
timeFrame: 24 months
measure: Health Assessment Questionnaire (HAQ-PROMIS)
timeFrame: 24 months
measure: Medical Outcomes Study Short-Form 36-item (SF-36)
timeFrame: 24 months
measure: Dual Energy X-ray Absorptiometry (DEXA) of spine and hip
timeFrame: 24 months
measure: Disease Activity Score (DAS)
timeFrame: 24 months
measure: Ultrasonography (synovitis)
timeFrame: 24 months
measure: Magnetic Resonance Imaging (MRI) of dominant hand
timeFrame: 12 months
measure: American College of Rheumatology (ACR) response
timeFrame: 12 months
measure: European League Against Rheumatism (EULAR) response
timeFrame: 12 months
measure: Remission
timeFrame: 12 months
measure: Work performance
timeFrame: 12 months
measure: Conventional radiography
timeFrame: 12 months
measure: The RA Impact of Disease (RAID) score
timeFrame: 12 months
measure: Health Assessment Questionnaire (HAQ-PROMIS)
timeFrame: 12 months
measure: Medical Outcomes Study Short-Form 36-item (SF-36)
timeFrame: 12 months
measure: Dual Energy X-ray Absorptiometry (DEXA) of spine and hip
timeFrame: 12 months
measure: Ultrasonography (synovitis)
timeFrame: 12 months
measure: Disease Activity Score (DAS)
timeFrame: 12 months
Other outcomes:
Locations:
city: Sandvika
country: Norway
facility: Martina Hansens Hospital AS
state: Bærum
city: Moss
country: Norway
facility: Sykehuset Østfold HF, Dept. of Rheumatology
state: Fredrikstad
city: Bergen
country: Norway
facility: Helse Bergen HF, Haukeland University Hospital, Dept. of Rheumatology
city: Drammen
country: Norway
facility: Vestre Viken HF, Dept. of Rheumatology
city: Haugesund
country: Norway
facility: Haugesund Sanitetsforening Revmatismesykehus
city: Kristiansand
country: Norway
facility: Sørlandet Sykehus HF, Dept. of Rheumatology
city: Kristiansand
country: Norway
facility: Revmatologene bendvold/Dovland
city: Oslo
country: Norway
facility: Diakonhjemmet Sykehus AS, Dept. of Rheumatology
city: Tromsø
country: Norway
facility: Universitetssykehuset Nord-Norge HF, Dept. of Rheumatology
city: Trondheim
country: Norway
facility: St Olavs Hospital HF, Dept. of Rheumatology
city: Ålesund
country: Norway
facility: Helse Sunnmøre HF, Dept. of Rheumatology
Study officials:
affiliation: Diakonhjemmet Hospital AS
name: Tore K Kvien, MD, PhD
role: STUDY_DIRECTOR
References:
citation: Sundin U, Aga AB, Skare O, Nordberg LB, Uhlig T, Hammer HB, van der Heijde D, Kvien TK, Lillegraven S, Haavardsholm EA; ARCTIC study group. Conventional versus ultrasound treat to target: no difference in magnetic resonance imaging inflammation or joint damage over 2 years in early rheumatoid arthritis. Rheumatology (Oxford). 2020 Sep 1;59(9):2550-2555. doi: 10.1093/rheumatology/kez674.
citation: Paulshus Sundlisaeter N, Olsen IC, Aga AB, Hammer HB, Uhlig T, van der Heijde D, Kvien TK, Lillegraven S, Haavardsholm EA; ARCTIC study group. Predictors of sustained remission in patients with early rheumatoid arthritis treated according to an aggressive treat-to-target protocol. Rheumatology (Oxford). 2018 Nov 1;57(11):2022-2031. doi: 10.1093/rheumatology/key202.
citation: Jonsson MK, Hensvold AH, Hansson M, Aga AB, Sexton J, Mathsson-Alm L, Cornillet M, Serre G, Lillegraven S, Fevang BS, Catrina AI, Haavardsholm EA. The role of anti-citrullinated protein antibody reactivities in an inception cohort of patients with rheumatoid arthritis receiving treat-to-target therapy. Arthritis Res Ther. 2018 Jul 13;20(1):146. doi: 10.1186/s13075-018-1635-7.
citation: Paulshus Sundlisaeter N, Aga AB, Olsen IC, Hammer HB, Uhlig T, van der Heijde D, Kvien TK, Lillegraven S, Haavardsholm EA; ARCTIC study group. Clinical and ultrasound remission after 6 months of treat-to-target therapy in early rheumatoid arthritis: associations to future good radiographic and physical outcomes. Ann Rheum Dis. 2018 Oct;77(10):1421-1425. doi: 10.1136/annrheumdis-2017-212830. Epub 2018 Jun 22.
citation: Nordberg LB, Lillegraven S, Aga AB, Sexton J, Lie E, Hammer HB, Olsen IC, Uhlig T, van der Heijde D, Kvien TK, Haavardsholm EA. The Impact of Ultrasound on the Use and Efficacy of Intraarticular Glucocorticoid Injections in Early Rheumatoid Arthritis: Secondary Analyses From a Randomized Trial Examining the Benefit of Ultrasound in a Clinical Tight Control Regimen. Arthritis Rheumatol. 2018 Aug;70(8):1192-1199. doi: 10.1002/art.40494. Epub 2018 Jun 29.
citation: Jonsson MK, Sundlisaeter NP, Nordal HH, Hammer HB, Aga AB, Olsen IC, Brokstad KA, van der Heijde D, Kvien TK, Fevang BS, Lillegraven S, Haavardsholm EA. Calprotectin as a marker of inflammation in patients with early rheumatoid arthritis. Ann Rheum Dis. 2017 Dec;76(12):2031-2037. doi: 10.1136/annrheumdis-2017-211695. Epub 2017 Aug 16.
citation: Aga AB, Berner Hammer H, Christoffer Olsen I, Uhlig T, Kvien TK, van der Heijde D, Fremstad H, Madland TM, Lexberg AS, Haukeland H, Rodevand E, Hoili C, Stray H, Noraas AL, Widding Hansen IJ, Bakland G, Lillegraven S, Lie E, Haavardsholm EA. Development of a feasible and responsive ultrasound inflammation score for rheumatoid arthritis through a data-driven approach. RMD Open. 2016 Dec 16;2(2):e000325. doi: 10.1136/rmdopen-2016-000325. eCollection 2016.
citation: Haavardsholm EA, Aga AB, Olsen IC, Lillegraven S, Hammer HB, Uhlig T, Fremstad H, Madland TM, Lexberg AS, Haukeland H, Rodevand E, Hoili C, Stray H, Noraas A, Hansen IJ, Bakland G, Nordberg LB, van der Heijde D, Kvien TK. Ultrasound in management of rheumatoid arthritis: ARCTIC randomised controlled strategy trial. BMJ. 2016 Aug 16;354:i4205. doi: 10.1136/bmj.i4205.
citation: Nordberg LB, Lillegraven S, Lie E, Aga AB, Olsen IC, Hammer HB, Uhlig T, Jonsson MK, van der Heijde D, Kvien TK, Haavardsholm EA; and the ARCTIC working group. Patients with seronegative RA have more inflammatory activity compared with patients with seropositive RA in an inception cohort of DMARD-naive patients classified according to the 2010 ACR/EULAR criteria. Ann Rheum Dis. 2017 Feb;76(2):341-345. doi: 10.1136/annrheumdis-2015-208873. Epub 2016 Apr 19.
citation: Aga AB, Hammer HB, Olsen IC, Uhlig T, Kvien TK, van der Heijde D, Fremstad H, Madland TM, Lexberg AS, Haukeland H, Rodevand E, Hoili C, Stray H, Bendvold AN, Soldal DM, Bakland G, Lie E, Haavardsholm EA. First step in the development of an ultrasound joint inflammation score for rheumatoid arthritis using a data-driven approach. Ann Rheum Dis. 2016 Aug;75(8):1444-51. doi: 10.1136/annrheumdis-2015-207572. Epub 2015 Jun 17.