Background/Purpose:

The primary aim of this study was to analyse serum levels differences of angiogenic and inflammatory biomarkers between SDAI, CDAI, ACR, DAS28 and sonographic remission in patients with RA. As secondary objective, we tried to find clinical, serological or ultrasound biomarkers of radiographic progression and clinical flares in RA patients in clinical remission.

Methods:

We selected patients with RA in clinical remission (defined as DAS28-ESR<2.6 for > 6 months) tested by two independent rheumatologists. Clinical, epidemiological, demographic and serological data were analyzed. PDUS of knees and hands was performed by a sonographer with an ultrasound scanner with a linear probe of 8-12 MHz. Serum levels of biomarkers of inflammation/angiogenesis were determined by Quantibody® Human Array. Patients were classified according to 6 sets of remission criteria: SDAI (<3.3), CDAI (<2.8), ACR/EULAR, DAS28-ESR (<2.6), Doppler (score Doppler=0) and UdAS (ultrasound defined active synovitis: no joints with SH>2+PD). A clinical and radiographic follow-up of the patients was done along 5 years. Clinical flare was defined as the loss of remission (DAS28-ESR>2.6) and change on the baseline treatment for RA. Radiographic progression was defined as the new appearance of erosions in hands or feet.

Results:

60 patients with RA were collected. 76% female, aged (mean) 53 years; disease duration 110 months. Sixteen (26%) patients were taking oral prednisone (<5 mg/day), 47 (76%) conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs), and 27 (45%) biological therapies. At baseline, 67% of patients had PD signal and 48% fulfilled criteria for previously defined UdAS. Although patients in sonographic remission (both Doppler and UdAS) had lower levels of inflammatory biomarkers such as IL-6, IL-17 or IL-23, no significant differences were found between the 6 sets of remission criteria. Angiogenic biomarkers such as CXCL6 (0.039), ENA78 (0.007), SDF1 (0.047) and VEGF-R1 (0.025) were significantly lower in patients fulfilling CDAI remission. Patients with no PD signal (0.009) and no UdAS (0.006) had significantly lower levels of bFGF. After 5 years of follow-up, 12 patients (20%) flared and 14 (23.3%) had radiographic progression. No significant differences were found in flares or X-ray progression between the 6 sets of remission criteria.

Patients fulfilling UdAS but not those with only PD, had more radiographic progression (p=0.014). Patients on biological therapy had less clinical flares along the 5 years of follow-up (p=0.049). Finally, patients with more CD20 + cells infiltrates in sinovial membrane had also more radiographic progression (p=0.033).

Conclusion:

RA patients in CDAI remission had significantly-lower levels of angiogenic cytokines. Remission according to DAS28-ESR did not show worse clinical or radiographic progression after 5 years of follow-up. Noteworthy, UdAS and CD20+ cells infiltrates were both significant factors of radiographic progression.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/usefullness-of-serum-angiogenic-and-proinflammatory-cytokines-to-discriminate-between-6-sets-of-remission-criteria-and-biomarkers-of-radiographic-progression-and-clinical-flare-in-ra-in-clinical-remis/