Three‐Year Clinical Outcome Following Baseline Magnetic Resonance Imaging in Anti–Citrullinated Protein Antibody–Positive Arthralgia Patients: An Exploratory Study

Advanced imaging may be useful in the detection of subclinical synovitis (i.e., synovitis that cannot be detected by clinical examination) in anti–citrullinated protein antibody (ACPA)–positive arthralgia patients, and it may contribute to timely assessment of which individuals will eventually develop rheumatoid arthritis (RA) (1,2). Therefore, in this pilot study we investigated whether magnetic resonance imaging (MRI) can visualize subclinical inflammation in the hands and/or wrists of ACPA-positive arthralgia patients, and we determined the relationship between baseline MRI and development of clinical arthritis during 3 years of followup. MRI scans in healthy volunteers were included for comparison. The study was embedded in a cohort study that recruited seropositive arthralgia patients at the rheumatology outpatient clinics of the VU University Medical Center and Jan van Breemen Research Institute Reade (3). During 26 months, all arthralgia patients with positive ACPA status (3) (independent of IgM–rheumatoid factor status) were consecutively asked to participate in the present MRI substudy. Inclusion and exclusion criteria have been reported previously (2,3). Baseline MRI was performed on 28 included patients and 4 healthy volunteers without a history of joint disorders or clinical arthritis. Development of clinical arthritis was monitored according to the schedule of the cohort study during at least 3 consecutive years. MRI sequences (Siemens Sonata 1.5T MR scanner) were chosen according to Outcome Measures in Rheumatology (OMERACT) guidelines (4). STIR and 3-dimensional T1-weighted magnetization-prepared rapid gradient-echo images were obtained before and after intravenous gadolinium administration. Synovitis and bone marrow edema were scored by 2 independent observers (NA, CD) according to the OMERACT RA MRI Scoring (RAMRIS) system (4). The MRI protocol included scanning of all proximal interphalangeal (PIP) joints (PIP joints 1–5), metacarpophalangeal (MCP) joints (MCP joints 1–5), and wrist joints of both hands. At the patient level, MRI positivity was defined as the presence of synovitis and/or bone marrow edema in at least 1 joint/bone. Individual cumulative MRI scores (range 0–288) were calculated by summing synovitis and bone marrow edema scores of each hand/wrist joint. At baseline, the median age of the 28 patients was 44 years (interquartile range [IQR] 37–53 years). Twenty-three patients (82%) were women. The median duration of arthralgia was 15 months (IQR 11–35 months). The median age of the 4 healthy controls (1 man, 3 women) was 31 years (IQR 26–56 years). At baseline, MRI abnormalities were frequently found. In 26 of 28 patients (93%), MRI synovitis was present in 1 joint of both hands/wrists (Figure 1A). Ten of 26 patients had a synovitis score of 2 in 1 joint. A synovitis score of 3 was not observed. Bone marrow edema was present in only 3 of 28 patients (11%). MRIs in all healthy controls showed signs of mild synovitis (score of 1) in 1 joint (range 3–23). A score of 2 for synovitis was found in 1 joint of 1 healthy control. Bone marrow edema was not observed on MRIs in healthy controls. The presence of MRI abnormalities at baseline was not associated with dichotomous outcome of development of clinical arthritis (yes/no). Twelve of 28 patients (43%) developed clinical arthritis and were subsequently diagnosed as having RA according to the American College of Rheumatology/European League Against Rheumatism 2010 classification criteria (5). In 10 of 12 patients, arthritis was observed in hand and/or wrist joints. At the patient level, 11 of 12 patients who developed clinical arthritis and all 16 patients who did not develop clinical arthritis had a positive baseline Figure 1. A, Baseline T1-weighted contrast-enhanced magnetic resonance imaging (MRI) scan of the hand/wrist joints of an anti– citrullinated protein antibody (ACPA)–positive arthralgia patient who developed arthritis in hand/wrist joints during 3-year followup. Arrows indicate MRI signs of synovitis (score of 2). B, Cumulative MRI scores (including score of 1 for synovitis and bone marrow edema) of patients with and those without development of arthritis during 3-year followup. Symbols represent individual patients; horizontal bars show the median. C, Survival curves for all included patients, comparing the group with an MRI synovitis score of 2 in at least 1 joint (solid line) and the group with an MRI synovitis score of 1 in at least 1 joint (dashed line). Patients with a synovitis score of 2 developed arthritis faster than those with a synovitis score of 1. Plus sign indicates a censored patient. D, Cumulative MRI scores (including score of 1 for synovitis and bone marrow edema) in relation to age, in individual ACPA-positive arthralgia patients and individual healthy controls.