Macrophage-targeting positron emission tomography (PET) may be a useful tool to detect subclinical synovitis in patients with early rheumatoid arthritis (RA), according to a new study.
This PET technique could even distinguish between patients with and without a flare, the study suggested.
A previous study found this approach promising for identifying subclinical synovitis related to short-term flares in patients with longstanding disease, but such research has not been conducted in early RA patients.
The new results, published in Arthritis Research & Therapy, “suggest that subclinical macrophage activity can be present in treated RA patients with clinically quiescent disease, regardless of disease duration,” wrote the authors, led by Yoony Y.J. Gent, Department of Rheumatology, VU University Medical Center, Amsterdam, the Netherlands.
Since subclinical disease activity and frequent flares negatively impact clinical outcome, these findings strengthen the case for adding imaging to determine the prognosis of RA patients with mild disease activity without clinically apparent synovitis, they said.
PET depicts biological targets and can be used for sensitive detection of inflammation at the molecular and cellular level. Macrophage-targeting PET tracers can visualize inflammatory processes.
The study included 25 RA patients with a mean disease duration of 9 months. They had achieved a state of “minimal disease activity” with intensive disease-modifying anti-rheumatic drug (DMARD) combination treatment (methotrexate with or without sulfasalazine and high- or moderate-dose prednisolone) and had no apparent synovitis, defined as a Disease Activity Score (DAS) in 44 joints of less than 1.6, and no tender or swollen joints.
Researchers considered a flare as at least one swollen joint during a 44-joint examination.
For the PET protocol, researchers imaged left and right metacarpophalangeal (MCP), proximal interphalangeal (PIP), and both wrist joints, for a total of 22 joints per patient, and scored these for tracer uptake as: 0 (absent), 1 (faint), 2 (moderate), or 3 (intense). After factoring background uptake, they considered joints to be positive if there was a final score of at least 1. They classified patients as positive if they had at least one PET-positive joint.
The study found that 11 subjects (44%) were PET-positive. At the joint level, 6% of joints were PET-positive. The most frequent positive PET score was 1 and no joints scored 3.
More than half (56%) of the patients developed a flare within a year (eight of 11 PET-positive and six of 14 PET-negative subjects). Six flared in the scan regions (hands or wrists) and five were PET-positive.
The same pattern was seen with cumulative PET scores: median scores were significantly higher in patients with a flare in the hands or wrists than in those without a flare.
The results were similar when the definition for a flare was changed to having two swollen joints instead of one.
Using an MRI scanner, researchers obtained images of the same joints as with PET in 24 patients, and scored for the presence of synovitis and bone marrow edema, both signs of disease activity. Joints were considered positive if synovitis or bone edema were scored at least 1. Patients were classified as positive if they had at least one positive joint.
For every patient, a cumulative MRI score was calculated by summing all individual synovitis plus bone marrow edema joint scores on both hands and wrists.
The median cumulative score of all MRI scans was 10. All MRI scans were scored positive — so all PET-positive patients (n=11) also had positive MRI results. Vice versa, 54% of patients with a positive MRI scan had a negative PET scan. Bone marrow edema was found in 46% of patients.
There was no difference in median cumulative MRI scores between patients with and without a flare.
Because of its high sensitivity, MRI may detect subclinical disease activity such as subtle signs of inflammation, but some of these MRI abnormalities may have no clinical relevance, wrote the authors.
“Our study suggests higher specificity for macrophage-targeted PET both for dichotomous outcome (PET and MRI positivity at a patient level; yes — no) and for the cumulative score.”
The diagnostic test value of PET could be increased if the scan region was expanded to the whole body, the authors added.
Future studies in larger study populations are warranted to prove or validate the clinical usefulness of this PET scanning approach as a predictive tool for flare in RA.
A limitation of the study was that conclusions could not be reached regarding PET and MRI findings in relation to radiological outcome because of very low rates of progression overall.