Aiming for Remission in Rheumatoid Arthritis (RA) - the ARCTIC Trial

Conditions

Rheumatoid Arthritis

Keywords

rheumatoid arthritis, ultrasonography, remission, imaging remission, tight control, treat to target

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.

Ulf Sundin, Anna‐Birgitte Aga, Øivind Skare, Lena Bugge Nordberg, Till Uhlig et al. (11 authors)

Lara D. Veeken2019-12-1818 citations

10.1093/rheumatology/kez674

The role of anti-citrullinated protein antibody reactivities in an inception cohort of patients with rheumatoid arthritis receiving treat-to-target therapy.

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.

2018-07-1315 citations

10.1186/s13075-018-1635-7

Clinical and ultrasound remission after 6 months of treat-to-target therapy in early rheumatoid arthritis: associations to future good radiographic and physical outcomes.

Paulshus Sundlisæter N, Aga AB, Olsen IC, Hammer HB, Uhlig T, van der Heijde D, Kvien TK, Lillegraven S, Haavardsholm EA, ARCTIC study group.

2018-06-2226 citations

10.1136/annrheumdis-2017-212830

Predictors of sustained remission in patients with early rheumatoid arthritis treated according to an aggressive treat-to-target protocol

Nina Paulshus Sundlisæter, Inge Christoffer Olsen, Anna‐Birgitte Aga, Hilde Berner Hammer, Till Uhlig et al. (20 authors)

Lara D. Veeken2018-06-2028 citations

10.1093/rheumatology/key202

Calprotectin as a marker of inflammation in patients with early rheumatoid arthritis.

Jonsson MK, Sundlisæter NP, Nordal HH, Hammer HB, Aga AB, Olsen IC, Brokstad KA, van der Heijde D, Kvien TK, Fevang BS, Lillegraven S, Haavardsholm EA.

2017-08-1638 citations

10.1136/annrheumdis-2017-211695

Development of a feasible and responsive ultrasound inflammation score for rheumatoid arthritis through a data-driven approach

Anna‐Birgitte Aga, Hilde Berner Hammer, Inge Christoffer Olsen, Till Uhlig, Tore K Kvien et al. (19 authors)

RMD Open2016-12-0114 citations

10.1136/rmdopen-2016-000325

Ultrasound in management of rheumatoid arthritis: ARCTIC randomised controlled strategy trial

Espen A. Haavardsholm, Anna‐Birgitte Aga, Inge Christoffer Olsen, Siri Lillegraven, Hilde Berner Hammer et al. (19 authors)

BMJ2016-08-16283 citations

10.1136/bmj.i4205

Patients with seronegative RA have more inflammatory activity compared with patients with seropositive RA in an inception cohort of DMARD-naïve patients classified according to the 2010 ACR/EULAR criteria.

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.

2016-04-1984 citations

10.1136/annrheumdis-2015-208873

First step in the development of an ultrasound joint inflammation score for rheumatoid arthritis using a data-driven approach.

Aga AB, Hammer HB, Olsen IC, Uhlig T, Kvien TK, van der Heijde D, Fremstad H, Madland TM, Lexberg ÅS, Haukeland H, Rødevand E, Høili C, Stray H, Bendvold AN, Soldal DM, Bakland G, Lie E, Haavardsholm EA.

2015-06-1714 citations

10.1136/annrheumdis-2015-207572

Interventions

DEVICEUltrasonography

Standardized ultrasonographic assessment of 32 joints, assessed for both grey scale synovitis and power doppler signal, at each visit. Dose escalations based on DAS response in combination with change in US score. All joints with US Power Doppler signal are targets for intra articular injections.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 75 Years

Healthy volunteers

No

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

Design outcomes

Primary

Measure	Time frame	Description
Complete clinical Disease Activity Score (DAS) remission	24 months	Specifically, the primary endpoint will be the proportion of patients with all the following criteria met at the end of the study (at 24 months): * DAS score \< 1.6 at visits 11, 12 and 13 (after 16, 20 and 24 months) * Absence of swollen joints at visits 11, 12 and 13 (after 16, 20 and 24 months) * No radiological progression between visit 11 (16 months) and visit 13 (24 months)

Secondary

Measure	Time frame	Description
Magnetic Resonance Imaging (MRI) of dominant hand	24 months	MRIs of dominant hand are scored according to the Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS) for synovitis, bone marrow edema and erosions, and Haavardsholm tenosynovitis score, as well as a novel joint space narrowing score will be applied.
American College of Rheumatology (ACR) response	24 months	Proportion of patients with ACR20, ACR50, ACR70 and ACR90 response.
Remission	24 months	Various definitions of remission will be calculated, including DAS-remission, ACR-remission, Simplified Diseases Activity Index (SDAI) remission and Clinical Disease Activity Index (CDAI) remission
Work performance	24 months	1. Absenteeism (work time missed) 2. Presenteeism (impairment at work / reduced on-the-job effectiveness) 3. Work productivity loss (overall work impairment / absenteeism plus presenteeism) 4. Activity Impairment
Conventional radiography	24 months	Radiographs of hands (posterior/anterior) and foot (anterior/posterior) will be taken at baseline, 3, 6, 12, 16 and 24 months. The modified Sharp van der Heijde Score (vdHSS) will be calculated, including an erosion score and a joint space narrowing score.
The RA Impact of Disease (RAID) score	24 months	The RAID includes seven domains with the following relative weights: pain (21%), functional disability (16%), fatigue (15%), emotional well-being (12%), sleep (12%), coping (12%) and physical well-being (12%).
European League Against Rheumatism (EULAR) response	24 months	EULAR good, moderate and non-response
Health Assessment Questionnaire (HAQ-PROMIS)	24 months	The HAQ-PROMIS is a questionnaire evaluating the physical function in patients with RA.
Medical Outcomes Study Short-Form 36-item (SF-36)	24 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.
Dual Energy X-ray Absorptiometry (DEXA) of spine and hip	24 months	Bone density measurements (DEXA hip and spine, both Z- and T-scores as well as bone mineral density) will be performed at baseline and after 12 and 24 months.
Disease Activity Score (DAS)	24 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
Ultrasonography (synovitis)	24 months	36 joints and 2 tendons will be scored for both grey scale and power doppler synovitis on a 0-3 scale.
EuroQol-5 Dimension (EQ-5D)	24 months	EQ-5D is a standardised instrument for use as a measure of health outcome.

Countries

Norway

Outcome results

None listed