Skip to main content

Do biologic therapies reduce aortic inflammation in rheumatoid arthritis patients?

Abstract

Objectives

Rheumatoid arthritis (RA) patients have an increased risk of cardiovascular disease (CVD). In the present study, we evaluated the inflammatory activity of the ascending aorta in RA patients who received biological treatment.

Methods

We assessed the aortic wall inflammation of RA patients using 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography before and after 6 months of biologic therapies. We also compared the inflammatory activity at the aortic wall in RA patients with remission or low disease activity (RLDA) and those with moderate or high disease activity (MHDA). The aortic uptake was measured by the standardized uptake value (SUV) and the target-to-background ratio (TBR).

Results

A total of 64 patients were included in the analysis (mean age, 58.4 ± 13.8 years old; female, 77%). The Disease Activity Score for 28 joints (DAS28) erythrocyte sedimentation rate (ESR) had significantly decreased after 6 months: from 5.0 ± 1.2 to 3.3 ± 1.2 (p < 0.001). The FDG uptake in the ascending aorta changed from baseline to 6 months, showing a maximum SUV (SUVmax) of 1.83 ± 0.34 to 1.90 ± 0.34 (p = 0.059) and TBR of 1.71 ± 0.23 to 1.75 ± 0.24 (p = 0.222). The SUVmax and TBR after 6 months were significantly higher in the RLDA group than in the MHDA group (2.05 ± 0.32 vs. 1.79 ± 0.33 (p = 0.002) and 1.89 ± 0.33 vs. 1.65 ± 0.20 (p = 0.001), respectively). The percentage of monocytes also significantly increased from baseline to 6 months: from 5.9 ± 1.6 to 6.9 ± 2.6 (p = 0.032).

Conclusion

The inflammation activity at the ascending aorta in RA patients did not change significantly after 6 months of biological treatment. RA patients with a low disease activity or in clinical remission after 6 months of biological treatment still had an increased inflammatory activity at the aortic wall.

Background

Rheumatoid arthritis (RA) increases the risk of cardiovascular disease (CVD) [1,2,3]. An accelerated progression of atherosclerosis leads to an increased mortality in RA patients [4,5,6,7,8,9,10]. Because both an inflamed synovial membrane and atherosclerotic plaque share important common pathological processes, chronic systemic inflammation might accelerate the development of atherosclerosis in RA patients [10]. Previous studies have demonstrated that atherosclerosis is more prevalent in the RA population than in healthy individuals [4,5,6,7,8,9].

18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) can be used to evaluate the joints in RA patients [11,12,13,14,15,16]. In addition, FDG PET/CT has also been widely used to evaluate atherosclerosis, since the 18F-FDG uptake reflects the glucose metabolism of macrophages in atherosclerotic plaque [17,18,19,20,21]. However, while FDG PET/CT is a highly reproducible method of evaluating arterial inflammation, there have been few reports regarding its utility in assessing aortic inflammation in RA patients.

In the present study, we assessed the ascending aortic wall inflammation in RA patients who received biologic therapies using 18F-FDG PET/CT. We also compared the inflammatory activity at the aortic wall in RA patients in remission or with a low disease activity (RLDA) and those with moderate or high disease activity (MHDA) after biologic treatment.

Materials and methods

Study population

Sixty-four RA patients who underwent whole-body 18F-FDG PET/CT at baseline and 6 months after the initiation of biologic therapies at Gunma University Hospital were enrolled in this study. All patients were diagnosed with RA according to the American College of Rheumatology criteria revised in 1987 and had a history of inadequate clinical response to previous treatments with nonbiological disease-modifying antirheumatic drugs (DMARDs), such as methotrexate (MTX). Therefore, these patients had been recommended for treatment with biologics.

The study protocol was approved by the Institutional Review Board of Gunma University Hospital. Written, informed consent was obtained from each patient before they participated in the study.

Imaging acquisition

Whole-body 18F-FDG PET/CT was performed using a PET/CT scanner (Biograph 16; Siemens Medical Solutions Inc., Malvern, PA, USA) before and 6 months after the initiation of biologic therapies. In brief, 18F-FDG (5 MBq/kg) was injected intravenously after at least 6 h of fasting. Patients were imaged approximately 60 min after FDG injection in the supine position. A non-contrast-enhanced CT scan (140 kV, 120–240 mAs) for attenuation correction and anatomic co-registration was obtained before PET imaging. PET imaging was performed in the 3-dimensional mode with 3 min per bed position and slice thickness of 3.27 mm. The PET images were reconstructed using an ordered-subsets expectation-maximization algorithm into 128 × 128 matrices as previously described [11, 13].

Imaging analyses

Image analyses were performed using the syngo.via software program (Siemens Healthcare, Erlangen, Germany). An independent radiologist blinded to the clinical data analyzed all of the PET/CT images. According to the recommendation of the Cardiovascular Committee of the European Association of Nuclear Medicine (EANM) [22], we used the maximum standardized uptake value (SUVmax) and the target-to-background ratio (TBR) as parameters for the FDG uptake in the ascending aorta. The SUVmax and TBR correlate with histological markers of inflammation and have been used in several studies to measure the FDG uptake in the arterial wall [17, 18, 23, 24].

Ascending aorta inflammation was quantified within each region of interest (ROI), containing the arterial wall and the lumen, along the length of the ascending aorta. The ROIs were manually drawn every 5 mm on axial images, starting 1 cm above the origin of the left main coronary artery and ending at the merging point with the aortic arch. The SUV is determined as the radioactivity concentration (kBq/ml) within an ROI divided by the decay-corrected amount of injected dose per patient’s weight (kBq/g). The average of the SUVmax (mean SUVmax) for all ROIs of the entire ascending aorta was then calculated. Subsequently, the TBR was obtained as the mean SUVmax divided by the background SUVmax in the superior vena cava to correct for the blood activity.

Clinical and laboratory evaluations

RA disease activity was assessed using the Disease Activity Score for 28 joints (DAS28) based on the ESR at baseline and 6 months after the initiation of biologic therapies. We also measured the white blood cell (WBC) count, serum levels of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), matrix metalloproteinase-3 (MMP-3), anti-cyclic citrullinated peptide antibodies (ACPA), and rheumatoid factor antibodies (RF).

The patients were divided into 2 groups according to the DAS28-ESR at 6 months: RLDA in those with a DAS28-ESR < 3.2 and MHDA in those with a DAS28-ESR ≥ 3.2. The clinical parameters and FDG uptake for the ascending aorta at baseline were compared between these two groups.

Statistical analyses

Data analyses were performed using the IBM SPSS Statistics 25 software program (IBM Corp., Armonk, NY, USA). Data were expressed as the mean ± standard deviation for parametric variables, as the median and interquartile range for nonparametric variables, and as numbers and percentages for categorical variables. For the comparison of continuous data between two clinical response groups, an unpaired Student’s t-test was used. For the comparison of continuous data before and after treatment, paired Student’s t-test or Wilcoxon’s signed-rank test was used. For the comparison of categorical data, the chi-square test or Fisher’s exact test was used. A value of p < 0.05 was considered statistically significant.

Results

A total of 64 patients were included in the analysis (mean age, 58.4 ± 13.8 years old; females, 77%) (Table 1). The mean disease duration was 13.1 ± 11.8 years. A total of 70% of the patients received MTX, and 48% received prednisolone (PSL). Figure 1 shows the 18F-FDG PET/CT findings for a case at baseline and 6 months after the initiation of biologic therapy. The mean FDG uptake values for the ascending aorta and the clinical parameters at baseline and 6 months after the initiation of biologic treatments are shown in Table 2. Although all clinical parameters except for the ACPA were significantly decreased at 6 months compared with the baseline, the mean SUVmax and TBR were not significantly changed after 6 months (Table 2).

Table 1 The demographic characteristics and medication use of patients at baseline
Fig. 1
figure1

Typical 18F-FDG PET/CT images of the ascending aorta wall uptake at baseline and after 6 months of biologic therapy. Axial and coronal images of ascending aorta from a 65-year-old female patient who underwent treatment with infliximab. A At baseline, the mean SUVmax was 1.64, and the TBR was 1.63. B At 6 months, the mean SUVmax was 1.56, and the TBR was 1.44. SUVmax, maximum standardized uptake value; TBR, target-to-background ratio

Table 2 Changes in FDG parameters and clinical parameters after treatment

We compared the FDG uptake at the ascending aorta between the two groups (RLDA group vs. MHDA group) at baseline and after 6 months of treatment. Figure 2 shows the increases in the mean SUVmax and TBR values for the ascending aorta at 6 months after the initiation of treatment, especially in the RLDA group. The mean SUVmax value at 6 months was significantly higher in the RLDA group than in the MHDA group (2.05 ± 0.32 vs. 1.79 ± 0.33; p = 0.002). The TBR value at baseline was significantly higher in the RLDA group than in the MHDA group (1.79 ± 0.26 vs. 1.65 ± 0.19; p = 0.018). After 6 months, the TBR value was also significantly higher in the RLDA group than in the MHDA group (1.89 ± 0.33 vs. 1.65 ± 0.20; p = 0.001).

Fig. 2
figure2

FDG uptake parameters of the ascending aorta for the two clinical response groups. The mean SUVmax and TBR values of the ascending aorta at 6 months after biologic treatment were significantly higher in the group with a DAS28-ESR < 3.2 (indicating remission or low disease activity) than in the group with a DAS28-ESR ≥ 3.2 (indicating moderate or high disease activity). SUVmax, maximum standardized uptake value; TBR, target-to-background ratio; DAS28, Disease Activity Score in 28 joints; RLDA, remission or low disease activity; MHDA, moderate or high disease activity

At baseline, the WBC count and percentage of monocytes were significantly higher in the RLDA group than in the MHDA group (p = 0.005 and p = 0.035) (Table 3). Regarding the WBC subtypes at 6 months, there were significantly lower percentages of neutrophils (p < 0.001) and significantly higher percentages of lymphocytes (p < 0.001) in the RLDA group than in the MHDA group (Table 4). The percentage of monocytes significantly increased from baseline to 6 months (5.9 ± 1.6 to 6.9 ± 2.6; p = 0.032).

Table 3 The comparison of clinical parameters at baseline
Table 4 Counts for WBC subtypes at 6 months in the two groups

We compared the FDG uptake and clinical parameters between the groups with and without anti-tumor necrosis factor (TNF) drug treatment, but there were no significant differences between these two groups (data not shown).

Discussion

In the present study, we found that the inflammation activity of the ascending aorta in RA patients did not significantly change after 6 months of biologic treatment. RA patients with RLDA after 6 months had a significantly higher FDG uptake at the aortic wall than those with MDLA.

Biological agents showed beneficial effects on reducing RA symptoms and disease activity by suppressing inflammation. Since atherosclerosis is a chronic inflammation process, these drugs may be also effective in reducing CVD risk in RA. Previous reports have shown that 8-week anti-TNF-α therapy reduced aortic inflammation in RA patients [25]. However, the FDG uptake of the arterial wall after treatment was still significantly higher in RA patients than in the control group.

In our study, although the disease activity and serum markers of RA patients significantly decreased after 6 months of biologic treatment, the inflammatory activity of the ascending aorta still existed. This result indicated that the cardio-protective effects of biologic therapy might not apply to all RA patients at six months.

A cross-sectional study in the USA demonstrated that RA patients who needed anti-TNF therapy to continue their clinical remission had a greater FDG uptake at the ascending aorta than those receiving non-biological DMARDs [26]. In addition to the high disease activity before the biological treatment, our patients had a long disease duration after the onset of RA. These patients’ condition might have led to the remnant aortic inflammation after 6 months of biological treatment, even if their joints had a good clinical response to biological drugs. Our results indicated that if we were intending to use biological drugs to achieve a cardio-protective effect, we should ensure RA patients maintain a low disease activity for a long time.

The FDG uptake in the aortic wall was significantly higher in RA patients with RLDA than in those with MHDA at 6 months. This was a controversial result. However, as mentioned above, our follow-up period was only 6 months and thought to be insufficient to reduce systemic inflammation by RA. It is thus possible that a longer treatment period led to the reduced aortic inflammation in the RLDA group.

In addition, a 3-year, prospective, observational study in an Italian cohort clearly showed that the maintenance of remission was associated with a reduced risk of atherosclerosis [27]. Our results showed that while the use of biologic therapies had reduced the clinical symptoms at 6 months, the aortic wall inflammation in these patients persisted despite 6 months of biologic treatment. Therefore, tight control of the RA activity in these patients should be maintained, and their CVD risk should be carefully estimated.

In this study, we also noted an elevation of monocytes at baseline and at 6 months in the RLDA group. An increased activation of circulating monocytes has been reported in patients receiving anti-TNF therapy [26] and the elevations of monocyte subpopulation can be seen in RA patients with coronary artery atherosclerosis and are associated with an increased CVD risk [28, 29]. Furthermore, a previous in vivo imaging study reported that the peripheral blood mononuclear cell accumulation was correlated with the arterial wall inflammation assessed on hybrid single-photon emission computed tomography/CT [30]. These previous findings suggest that the increased percentage of monocytes might be involved in arterial wall inflammation in RA patients, even after biologic therapy.

Several limitations associated with the present study warrant mention. First, traditional cardiovascular risk factors could not be fully investigated because of the lack of such information. Second, the selection of biologic agents was left to each physician. Since different drugs have different mechanisms through which they act on RA pathogenesis, treatment bias may exist. Third, since FDG-PET/CT is a nuclear imaging modality, repeated examinations might lead to increased radiation exposure. Finally, this was a short-term study. To determine whether or not biological therapies are useful for reducing aortic inflammation and CVD risk in RA patients, further long-term follow-up research should be conducted.

Conclusions

We demonstrated that the inflammation activity of the ascending aorta in RA patients was not significantly altered after 6 months of biologic treatment. RA patients with a low disease activity or in clinical remission after 6 months of such treatment still had an increased inflammatory activity at the aortic wall.

Availability of data and materials

All data generated or analyzed during this study are included in this published article and its supplementary information file.

Abbreviations

ACPA:

Anti-cyclic citrullinated peptide antibody

CRP:

C-reactive protein

DAS:

Disease activity score

DMARDs:

Disease-modifying antirheumatic drugs

CVD:

Cardiovascular disease

EANM:

European association of nuclear medicine

ESR:

Erythrocyte sedimentation rate

FDG-PET/CT:

Fluorodeoxyglucose-positron emission tomography/computed tomography

RLDA:

RA patients in remission or with a low disease activity

MHDA:

RA patients with moderate or high disease activity

MMP-3:

Matrix metalloproteinase 3

MTX:

Methotrexate

PSL:

Prednisolone

RA:

Rheumatoid arthritis

RF:

Rheumatoid factor

ROI:

Region of interest

SUV:

Standardized uptake value

SUVmax:

Maximum standardized uptake value

TBR:

Target-to-background ratio

TNF:

Tumor necrosis factor

WBC:

White blood cell

References

  1. 1.

    Peters MJL, van Halm VP, Voskuyl AE, Smulders YM, Boers M, Lems WF, et al. Does rheumatoid arthritis equal diabetes mellitus as an independent risk factor for cardiovascular disease? A prospective study. Arthritis Care Res. 2009;61(11):1571–9. https://doi.org/10.1002/art.24836.

    Article  Google Scholar 

  2. 2.

    del Rincon ID, Williams K, Stern MP, Freeman GL, Escalante A. High incidence of cardiovascular events in a rheumatoid arthritis cohort not explained by traditional cardiac risk factors. Arthritis Rheumatism. 2001;44(12):2737–45. https://doi.org/10.1002/1529-0131(200112)44:12<2737::AID-ART460>3.0.CO;2-#.

  3. 3.

    Crowson CS, Liao KP, Davis JM 3rd, Solomon DH, Matteson EL, Knutson KL, et al. Rheumatoid arthritis and cardiovascular disease. Am Heart J. 2013;166(4):622–8 e1. https://doi.org/10.1016/j.ahj.2013.07.010.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  4. 4.

    Skeoch S, Cristinacce PLH, Williams H, Pemberton P, Xu D, Sun J, et al. Imaging atherosclerosis in rheumatoid arthritis: evidence for increased prevalence, altered phenotype and a link between systemic and localised plaque inflammation. Sci Rep. 2017;7(1):827. https://doi.org/10.1038/s41598-017-00989-w.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  5. 5.

    Jonsson SW, Backman C, Johnson O, Karp K, Lundstrom E, Sundqvist KG, et al. Increased prevalence of atherosclerosis in patients with medium term rheumatoid arthritis. J Rheumatol. 2001;28(12):2597–602.

  6. 6.

    Gonzalez-Juanatey C, Llorca J, Testa A, Revuelta J, Garcia-Porrua C, Gonzalez-Gay MA. Increased prevalence of severe subclinical atherosclerotic findings in long-term treated rheumatoid arthritis patients without clinically evident atherosclerotic disease. Medicine. 2003;82(6):407–13. https://doi.org/10.1097/01.md.0000101572.76273.60.

    Article  PubMed  Google Scholar 

  7. 7.

    Hannawi S, Haluska B, Marwick TH, Thomas R. Atherosclerotic disease is increased in recent-onset rheumatoid arthritis: a critical role for inflammation. Arthritis Res Ther. 2007;9(6):R116. https://doi.org/10.1186/ar2323.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  8. 8.

    Aubry M-C, Maradit-Kremers H, Reinalda MS, Crowson CS, Edwards WD, Gabriel SE. Differences in atherosclerotic coronary heart disease between subjects with and without rheumatoid arthritis. J Rheumatol. 2007;34(5):937–42.

    CAS  PubMed  Google Scholar 

  9. 9.

    Semb AG, Rollefstad S, Provan SA, Kvien TK, Stranden E, Olsen IC, et al. Carotid plaque characteristics and disease activity in rheumatoid arthritis. J Rheumatol. 2013;40(4):359–68. https://doi.org/10.3899/jrheum.120621.

    CAS  Article  PubMed  Google Scholar 

  10. 10.

    Skeoch S, Bruce IN. Atherosclerosis in rheumatoid arthritis: is it all about inflammation? Nat Rev Rheumatol. 2015;11(7):390–400. https://doi.org/10.1038/nrrheum.2015.40.

    CAS  Article  PubMed  Google Scholar 

  11. 11.

    Okamura K, Yonemoto Y, Arisaka Y, Takeuchi K, Kobayashi T, Oriuchi N, et al. The assessment of biologic treatment in patients with rheumatoid arthritis using FDG-PET/CT. Rheumatology. 2012;51(8):1484–91. https://doi.org/10.1093/rheumatology/kes064.

    CAS  Article  PubMed  Google Scholar 

  12. 12.

    Okamura K, Yonemoto Y, Okura C, Higuchi T, Tsushima Y, Takagishi K. Evaluation of tocilizumab therapy in patients with rheumatoid arthritis based on FDG-PET/CT. BMC Musculoskelet Disord. 2014;15(1):393. https://doi.org/10.1186/1471-2474-15-393.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  13. 13.

    Suto T, Okamura K, Yonemoto Y, Okura C, Tsushima Y, Takagishi K. Prediction of large joint destruction in patients with rheumatoid arthritis using 18F-FDG PET/CT and Disease Activity Score. Medicine. 2016;95(7):e2841. https://doi.org/10.1097/MD.0000000000002841.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  14. 14.

    Suto T, Yonemoto Y, Okamura K, Okura C, Kaneko T, Kobayashi T, et al. Predictive factors associated with the progression of large-joint destruction in patients with rheumatoid arthritis after biologic therapy: a post-hoc analysis using FDG-PET/CT and the ARASHI (assessment of rheumatoid arthritis by scoring of large-joint destruction and healing in radiographic imaging) scoring method. Modern Rheumatol. 2017;27(5):820–7. https://doi.org/10.1080/14397595.2016.1266132.

    CAS  Article  Google Scholar 

  15. 15.

    Yonemoto Y, Okamura K, Takeuchi K, Kaneko T, Kobayashi T, Okura C, et al. [18F]fluorodeoxyglucose uptake as a predictor of large joint destruction in patients with rheumatoid arthritis. Rheumatol Int. 2016;36(1):109–15. https://doi.org/10.1007/s00296-015-3331-0.

    CAS  Article  PubMed  Google Scholar 

  16. 16.

    Yonemoto Y, Okamura K, Kobayashi T, Kaneko T, Okura C, Suto T, et al. Predictive factors related to shoulder joint destruction in rheumatoid arthritis patients treated with biologics: a prospective study. Mod Rheumatol. 2017;27(4):587–92. https://doi.org/10.1080/14397595.2016.1245125.

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    Rudd JHF, Warburton EA, Fryer TD, Jones HA, Clark JC, Antoun N, et al. Imaging atherosclerotic plaque inflammation with [18F]-fluorodeoxyglucose positron emission tomography. Circulation. 2002;105(23):2708–11. https://doi.org/10.1161/01.CIR.0000020548.60110.76.

    CAS  Article  PubMed  Google Scholar 

  18. 18.

    Tawakol A, Migrino RQ, Bashian GG, Bedri S, Vermylen D, Cury RC, et al. In Vivo 18F-fluorodeoxyglucose positron emission tomography imaging provides a noninvasive measure of carotid plaque inflammation in patients. J Am Coll Cardiol. 2006;48(9):1818–24. https://doi.org/10.1016/j.jacc.2006.05.076.

    Article  PubMed  Google Scholar 

  19. 19.

    Græbe M, Pedersen SF, Borgwardt L, Højgaard L, Sillesen H, Kjær A. Molecular pathology in vulnerable carotid plaques: correlation with [18]-fluorodeoxyglucose positron emission tomography (FDG-PET). Eur J Vasc Endovasc Surg. 2009;37(6):714–21. https://doi.org/10.1016/j.ejvs.2008.11.018.

    Article  PubMed  Google Scholar 

  20. 20.

    Paulmier B, Duet M, Khayat R, Pierquet-Ghazzar N, Laissy J-P, Maunoury C, et al. Arterial wall uptake of fluorodeoxyglucose on PET imaging in stable cancer disease patients indicates higher risk for cardiovascular events. J Nuclear Cardiol. 2008;15(2):209–17. https://doi.org/10.1016/j.nuclcard.2007.10.009.

    Article  Google Scholar 

  21. 21.

    Rominger A, Saam T, Wolpers S, Cyran CC, Schmidt M, Foerster S, et al. 18F-FDG PET/CT identifies patients at risk for future vascular events in an otherwise asymptomatic cohort with neoplastic disease. J Nuclear Med. 2009;50(10):1611–20. https://doi.org/10.2967/jnumed.109.065151.

    Article  Google Scholar 

  22. 22.

    Bucerius J, Hyafil F, Verberne HJ, et al. Position paper of the Cardiovascular Committee of the European Association of Nuclear Medicine (EANM) on PET imaging of atherosclerosis. Eur J Nucl Med Mol Imaging. 2016;43(4):780–92. https://doi.org/10.1007/s00259-015-3259-3.

    Article  PubMed  Google Scholar 

  23. 23.

    Figueroa AL, Abdelbaky A, Truong QA, Corsini E, MacNabb MH, Lavender ZR, et al. Measurement of arterial activity on routine FDG PET/CT images improves prediction of risk of future CV events. JACC Cardiovasc Imaging. 2013;6(12):1250–9. https://doi.org/10.1016/j.jcmg.2013.08.006.

    Article  PubMed  Google Scholar 

  24. 24.

    Tawakol A, Fayad ZA, Mogg R, Alon A, Klimas MT, Dansky H, et al. Intensification of statin therapy results in a rapid reduction in atherosclerotic inflammation: results of a multicenter fluorodeoxyglucose-positron emission tomography/computed tomography feasibility study. J Am Coll Cardiol. 2013;62(10):909–17. https://doi.org/10.1016/j.jacc.2013.04.066.

    CAS  Article  PubMed  Google Scholar 

  25. 25.

    Maki-Petaja KM, Elkhawad M, Cheriyan J, Joshi FR, Ostor AJ, Hall FC, et al. Anti-tumor necrosis factor-alpha therapy reduces aortic inflammation and stiffness in patients with rheumatoid arthritis. Circulation. 2012;126(21):2473–80. https://doi.org/10.1161/CIRCULATIONAHA.112.120410.

    CAS  Article  PubMed  Google Scholar 

  26. 26.

    Bernelot Moens SJ, van der Valk FM, Strang AC, Kroon J, Smits LP, Kneepkens EL, et al. Unexpected arterial wall and cellular inflammation in patients with rheumatoid arthritis in remission using biological therapy: a cross-sectional study. Arthritis Res Ther. 2016;18(1):115. https://doi.org/10.1186/s13075-016-1008-z.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  27. 27.

    Ruscitti P, Cipriani P, Liakouli V, Iacono D, Pantano I, Margiotta DPE, et al. Subclinical and clinical atherosclerosis in rheumatoid arthritis: results from the 3-year, multicentre, prospective, observational GIRRCS (Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale) study. Arthritis Res Ther. 2019;21(1):204. https://doi.org/10.1186/s13075-019-1975-y.

    Article  PubMed  PubMed Central  Google Scholar 

  28. 28.

    Winchester R, Giles JT, Nativ S, Downer K, Zhang H-Z, Bag-Ozbek A, et al. Association of elevations of specific T cell and monocyte subpopulations in rheumatoid arthritis with subclinical coronary artery atherosclerosis. Arthritis Rheumatol. 2016;68(1):92–102. https://doi.org/10.1002/art.39419.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  29. 29.

    Ruiz-Limon P, Ortega-Castro R, Barbarroja N, Perez-Sanchez C, Jamin C, Patiño-Trives AM, et al. Molecular characterization of monocyte subsets reveals specific and distinctive molecular signatures associated with cardiovascular disease in rheumatoid arthritis. Front. Immunol. 10:1111. https://doi.org/10.3389/fimmu.2019.01111

  30. 30.

    van der Valk FM, Kroon J, Potters WV, Thurlings RM, Bennink RJ, Verberne HJ, et al. In vivo imaging of enhanced leukocyte accumulation in atherosclerotic lesions in humans. J Am Coll Cardiol. 2014;64(10):1019–29. https://doi.org/10.1016/j.jacc.2014.06.1171.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

None.

Funding

There has been no significant financial support for this work that could have influenced its outcome. The authors acknowledge the financial support provided by a UCB Japan Grant (UCBJ Grant) for the English proofreading and article processing charge of the journal.

Author information

Affiliations

Authors

Contributions

DTT and KO made substantial contributions to the design of the study; acquisition, analysis, and interpretation of the data; and writing of the manuscript. TS and YY participated in the design of the study, acquired the data, helped to draft the manuscript, and contributed to the revising of the manuscript critically. HS and TN participated in acquiring the data and critically contributing to the revising of the manuscript. YT and HC critically contributed to the revising of the manuscript enhancing its intellectual content and approving the final content of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Koichi Okamura.

Ethics declarations

Ethics approval and consent to participate

Ethical approval was obtained from the institutional review board of the Gunma University Hospital. Patients provided written informed consent before taking part in this study.

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Trang, D.A.M.T., Okamura, K., Suto, T. et al. Do biologic therapies reduce aortic inflammation in rheumatoid arthritis patients?. Arthritis Res Ther 23, 206 (2021). https://doi.org/10.1186/s13075-021-02585-w

Download citation

Keywords

  • Aortic inflammation
  • FDG PET/CT
  • Biologic therapy
  • Rheumatoid arthritis