Subclinical synovitis detected by macrophage PET, but not MRI, is related to short-term flare of clinical disease activity in early RA patients: an exploratory study.

Yoony Y J Gent,Marieke M Ter Wee,Alexandre E Voskuyl,Maarten Boers,Otto S Hoekstra,Cornelis Van Kuijk,Conny J Van Der Laken,Nazanin Ahmadi,Willem F Lems,Debby Den Uyl,Cristina Dowling

doi:10.1186/s13075-015-0770-7

Abstract

IntroductionResidual subclinical synovitis can still be present in joints of rheumatoid arthritis (RA) patients despite clinical remission and has been linked to ongoing radiological damage. The aim of the present study was to assess subclinical synovitis by positron emission tomography (PET; macrophage tracer 11C-(R)-PK11195) in early RA patients with minimal disease activity without clinically apparent synovitis (MDA); and its relationship with clinical outcome and magnetic resonance imaging (MRI), respectively.MethodsBaseline PET and MRI of hands/wrists were performed in 25 early MDA RA patients (DAS 44 < 1.6; no tender/swollen joints) on combined DMARD therapy. PET tracer uptake (semi-quantitative score: 0–3) and MRI synovitis and bone marrow edema (OMERACT RAMRIS) were assessed in MCP, PIP and wrist joints (22 joints/patient; cumulative score).ResultsEleven of 25 patients (44 %) showed enhanced tracer uptake in ≥ 1 joint. Fourteen of these 25 (56 %) patients developed a flare within 1 year: 8/11 (73 %) with a positive, and 6/14 (43 %) with a negative PET. In the latter, in 5/6 patients flare was located outside the scan region. Median cumulative PET scores of patients with a subsequent flare in the hands or wrists were significantly higher than those of patients without a flare (1.5 [IQR 0.8–5.3] vs 0.0 [IQR 0.0–1.0], p = 0.04); significance was lost when all flares were considered (1.0 [IQR 0.0–4.0] vs 0.0 [IQR 0.0–1.0], p = 0.10). No difference in cumulative MRI scores was observed between both groups.ConclusionsPositive PET scans were found in almost half of early RA patients with MDA. Patients with a subsequent flare in hand or wrist had higher cumulative PET scores but not MRI scores, suggesting that subclinical arthritis on PET may predict clinical flare in follow-up.

Highlights

Residual subclinical synovitis can still be present in joints of rheumatoid arthritis (RA) patients despite clinical remission and has been linked to ongoing radiological damage
We have recently shown that positron emission tomography (PET) and macrophage targeting is a promising technique for identification of longstanding RA patients with signs of subclinical synovitis related to short-term flare [15], but such studies have not yet been conducted in early RA patients
We explored whether 11C-(R)-PK11195 PET could depict residual disease activity in early RA patients that achieved a state of minimal disease activity (MDA) with intensive Disease-modifying anti-rheumatic drug (DMARD) combination treatment

Summary

Introduction

Residual subclinical synovitis can still be present in joints of rheumatoid arthritis (RA) patients despite clinical remission and has been linked to ongoing radiological damage. The aim of the present study was to assess subclinical synovitis by positron emission tomography (PET; macrophage tracer 11C-(R)-PK11195) in early RA patients with minimal disease activity without clinically apparent synovitis (MDA); and its relationship with clinical outcome and magnetic resonance imaging (MRI), respectively. There is evidence that progression of joint damage may proceed despite the absence of clinical synovitis—that is, in patients with MDA or in remission—presumably due to the presence of subclinical disease activity [11, 12]. MRI and US abnormalities are associated with future radiological damage and flaring in RA (remission) patients [12, 15,16,17,18,19,20], but this association is not very strong [21], leaving room for alternative imaging techniques that could further contribute to specificity

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