Abstract
BackgroundIncreasing numbers of patients (up to 40 %) with rheumatoid arthritis (RA) achieve remission, yet it remains to be elucidated whether this also normalizes their cardiovascular risk. Short-term treatment with TNF inhibitors lowers arterial wall inflammation, but not to levels of healthy controls. We investigated whether RA patients in long-term remission are characterized by normalized inflammatory activity of the arterial wall and if this is dependent on type of medication used (TNF-inhibitor versus nonbiological disease-modifying antirheumatic drugs (DMARDs)).MethodsArterial wall inflammation, bone marrow and splenic activity (index of progenitor cell activity) was assessed with 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in RA patients in remission (disease activity score (DAS28) <2.6 for >6 months) and healthy controls. We performed ex vivo characterization of monocytes using flow cytometry and a transendothelial migration assay.ResultsOverall, arterial wall inflammation was comparable in RA patients (n = 23) in long-term remission and controls (n = 17). However, RA subjects using current anti-TNF therapy (n = 13, disease activity score 1.98[1.8–2.2]) have an almost 1.2-fold higher 18F-FDG uptake in the arterial wall compared to those using DMARDs (but with previous anti-TNF therapy) (n = 10, disease activity score 2.24[1.3–2.5]), which seemed to be predominantly explained by longer duration of their rheumatic disease in a multivariate linear regression analysis. This coincided with increased expression of pro-adhesive (CCR2) and migratory (CD11c, CD18) surface markers on monocytes and a concomitant increased migratory capacity. Finally, we found increased activity in bone marrow and spleen in RA patients using anti-TNF therapy compared to those with DMARDs and controls.ConclusionsA subset of patients with RA in clinical remission have activated monocytes and increased inflammation in the arterial wall, despite the use of potent TNF blocking therapies. In these subjects, RA disease duration was the most important contributor to the level of arterial wall inflammation. This increased inflammatory state implies higher cardiovascular risk in these patients, who thus may require more stringent CV risk management.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-016-1008-z) contains supplementary material, which is available to authorized users.
Highlights
Increasing numbers of patients with rheumatoid arthritis (RA) achieve remission, yet it remains to be elucidated whether this normalizes their cardiovascular risk
Baseline characteristics For the positron emission tomography (PET)/computed tomography (CT) study, 23 consecutive RA patients in clinical remission for at least 6 months were included at the outpatient clinics of the Academic Medical Center (AMC) and the Amsterdam Rheumatology and Immunology Center, and compared to 17 age- and sex-matched healthy controls
DAS28, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) as well as percentage seropositive RA were distributed between the two groups, but disease duration and duration until first start of tumor necrosis factor (TNF) inhibition was significantly longer in the RA, TNF-inhibition group
Summary
Increasing numbers of patients (up to 40 %) with rheumatoid arthritis (RA) achieve remission, yet it remains to be elucidated whether this normalizes their cardiovascular risk. Short-term treatment with TNF inhibitors lowers arterial wall inflammation, but not to levels of healthy controls. We investigated whether RA patients in long-term remission are characterized by normalized inflammatory activity of the arterial wall and if this is dependent on type of medication used (TNF-inhibitor versus nonbiological disease-modifying antirheumatic drugs (DMARDs)). Short-term (8 weeks) TNF inhibition significantly reduced arterial wall inflammation in patients with active RA, it failed to completely normalize arterial inflammation to levels observed in control subjects [15]. Whether arterial inflammation can be further reduced during prolonged remission, with or without anti-TNF treatment, remains to be established
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