Long-term Outcomes of Patients with Rheumatoid Arthritis in Remission

Remission status will be assessed according to e.g the disease activity score DAS, the Simplified Disease Activity Index (SDAI) and ACR/EULAR Boolean 2.0 remission.

DAS includes the ritchie articular index, the swollen joint count (based on 44 joints), the ESR and the Patient's Global Assessment of disease activity on a VAS 0-100 mm (PGA). The following cut-points are used:

High disease activity: DAS > 3.7; Moderate disease activity: 3.7 ≥ DAS>2.4; Low disease activity: 2.4 ≥ DAS ≥ 1.6; In remission: DAS < 1.6

The SDAI includes tender and swollen joints (of 28), PGA, PhGA and CRP. According to SDAI, the following cut-points are used:

High disease activity: SDAI> 26.0; Moderate disease activity: 26.0 ≥ SDAI>11.0; Low disease activity: 11.0 ≥ SDAI > 3.3; In remission: SDAI ≤ 3.3

ACR/EULAR 2.0 remission is defined as the combination of tender joints ≤ 1, swollen joints ≤ 1, CRP ≤ 1 and patient global assessment ≤ 2 (on a scale 0-10).

The prevalence of DMARD-free remission

Radiographs of hands and feet. The van der Heijde-modified Sharp scoring method will be used, which assesses erosions in 16 joints of each hand (range, 0-5 for each joint) and in 6 joints of each foot (range, 0-10 per joint) and joint space narrowing in 15 joints for each hand and in 6 joints for each foot (range, 0-4 per joint).This gives scores for erosions on a scale from 0 to 280 and joint space narrowing on a scale from 0 to168, thus the total van der Heijde-modified Sharp score ranges from 0 to 448, with higher scores indicating greater joint damage.

Radiographs of hands and feet. The van der Heijde-modified Sharp scoring method will be used, which assesses erosions in 16 joints of each hand (range, 0-5 for each joint) and in 6 joints of each foot (range, 0-10 per joint) and joint space narrowing in 15 joints for each hand and in 6 joints for each foot (range, 0-4 per joint).This gives scores for erosions on a scale from 0 to 280 and joint space narrowing on a scale from 0 to168, thus the total van der Heijde-modified Sharp score ranges from 0 to 448, with higher scores indicating greater joint damage.

The images will be compared to the last corresponding images undertaken in the ARCTIC REWIND trial.

Progression will be calculated as e.g. annual increase in van der Heijde modified Sharp score ≥ 1 unit.

The following composite measures will be included: disease activity score (DAS), DAS based on 28 joint counts (DAS28), the simplified disease activity index (SDAI) and the clinical disease activity index (CDAI). These are based on tender and swollen joint counts, the PGA, acute phase reactants (except from CDAI), and, for SDAI and CDAI also the PhGA.

DAS: High disease activity: DAS > 3.7; Moderate disease activity: 3.7 ≥ DAS>2.4; Low disease activity: 2.4 ≥ DAS ≥ 1.6; In remission: DAS < 1.6

DAS28: High disease activity: DAS28 > 5.1; Moderate disease activity: 5.1 ≥ DAS28>3.2; Low disease activity: 3.2 ≥ DAS28 ≥ 2.6; In remission: DAS28 < 2.6

CDAI: High disease activity: CDAI > 22.0; Moderate disease activity: 22.0 ≥ CDAI>10.0; Low disease activity: 10.0 ≥ CDAI > 2.8; In remission: CDAI ≤ 2.8

SDAI: High disease activity: SDAI> 26.0;Moderate disease activity: 26.0 ≥ SDAI>11.0; Low disease activity: 11.0 ≥ SDAI; In remission SDAI ≤ 3.3

The Patient-Reported Outcomes Measurement Information (PROMIS) HAQ (Health Assessment Questionnaire ) 20-item short form will be used in this study. Each question has five response options, ranging in value from one to five. To find the total raw score, the sum of the values of the response to each question is calculated, giving a range in scores from 20 to 100 if all questions are answered. The total raw score should be translated into a T-score for each participant (either by standardized conversion tables or using item-level calibrations), which rescales the raw score into a standardized score with a mean of 50 and a standard deviation (SD) of 10. Therefore, a person with a T-score of 40 is one SD worse than average.

EuroQol-5 Dimensions three-level (EQ-5D-3L) is a utility instrument for measurement of health-related quality of life. It comprises the following five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, and extreme problems (labelled 1-3). They have no arithmetic properties and should not be used to derive a summary score. To derive the summary index score an appropriate value set is required, which provides values (weights) for each health state description according to the preferences of the general population of a country/region

0-100 visual analogue scale (VAS), with higher scores Indicating more disease activity

0-100 visual analogue scale (VAS), with higher scores Indicating more disease activity

Ultrasound joint inflammation will be assessed by use of a validated 0-3 semi-quantitative scoring system for power Doppler and grey scale with an ultrasound atlas as reference. In the total ultrasound score 32 joints will be included: Bilateral metacarpophalangeal (MCP) joint I-V, radiocarpal joint, distal radioulnar joint, intercarpal joint, elbow, knee, talocrural joint and metatarsophalangeal (MTP) joint I-V, yielding a maximum total score of 96. In addition to the 32 joints the following will be scored: Bilateral proximal Interphalangeal (PIP) 2 and 3 joints, extensor carpi ulnaris tendon and tibialis posterior tendon.

Assessment of 44 joints

Assessment of 44 tender joints

Assessed by Ritchie Articular index

Assessed by Dual-energy X-ray absorptiometry (DEXA)

Record of disease modifying antirheumatic drugs including corticosteroids

This will be assessed by The 36-item Short Form Health Survey (SF-36). The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability.

The eight sections are: vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, mental health or emotional wellbeing

Assessed by the Rheumatoid Arthritis Impact of Disease (RAID) score which is a patient-derived composite response index for use in clinical trials in RA. It includes seven domains which are scored between 0 and 10. The domains are given the following relative weights: pain (21%), functional disability (16%), fatigue (15%), emotional well-being (12%), sleep (12%), coping (12%) and physical well-being (12%).

The range of the final RAID value is 0-10 where higher scores indicate worse status.

Work Productivity and Activity Impairment Questionnaire: WPAI:RA. This is a questionnaire that quantifies health-related work productivity loss for those employed. Work time missed (absentism) and reduced on-the-job effectiveness are expressed in percentages. Overall work productivity loss (abstentism and presentism combined) is also expressed in percentages.

assessed by Systematic Coronary Risk Evaluation 2 (SCORE2), carotid intima-media thickness and plaques, and echocardiography

Blood test

Blood test

The Outcome Measures in Rheumatology (OMERACT) preliminary Rheumatoid Arthritis Flare Questionnaire version 2.1 will be used. The questionnaire includes information about variables deemed to be of relevance by both patients and health care professionals to describe and define RA flare. It assesses severity and duration of flare, self-management strategies related to flare, pain, function, fatigue, stiffness, participation, coping, and patients' self-assessment of joint tenderness and swelling.

Patients who classifies themselves as flaring rates the severity on a 11-point Numerical Rating Scale (0-10), the higher score the worse.

Questionnaire about comorbidities, including, but not limited to, cardiovascular/cerebrovascular disease, respiratory disease, diabetes mellitus, hypertension requiring treatment, cancer, fibromyalgia, osteoporosis, depression requiring treatment, joint replacements, hip fractures, and abdominal perforations.

Fatigue is self-reported with use of a visual analogue scale that ranges from 0 to 100 mm, with higher scores indicating more severe fatigue.

joint pain is self-reported with use of a visual analogue scale that ranges from 0 to 100 mm, with higher scores indicating more severe joint pain

Patient's acceptable symptom state