FRI0094 SIGNIFICANT IMPROVEMENT OF NT-PROBNP LEVELS IN RHEUMATOID ARTHRITIS PATIENTS TREATED WITH TOCILIZUMAB AND TOFACITINIB
Authors: H. Gerasimova, T. Popkova, I. Kirillova, M. Cherkasova, A. Martynova, D. Novikova, A. Lila
Journal: Annals of the Rheumatic Diseases (2020)

Background: N-terminal pro-brain natriuretic peptide (NT-proBNP) is a recognized predictor of congestive heart failure (CHF) and cardiovascular death. Rheumatoid arthritis (RA) patients (pts) were shown to have higher NT-proBNP concentrations than in general population, but it remains unclear, whether NT-proBNP levels are related to RA duration, activity or treatment. Objectives: To investigate the effect of interleukin 6 receptor inhibitor - tocilizumab (TCZ) and JAK inhibitor - tofacitinib (TOFA) on NT-proBNP levels in RA pts during a 12-month (m) follow-up period. Methods: The study enrolled 60pts (50women/10men) with the lack of efficacy/resistance and/or intolerance of basic anti-inflammatory drugs (DMARDs); median age was 55[42;61] years, median disease duration 55[29;120]m, with moderate to high activity (DAS28-5,1[4,6;6,1], serum positivity for rheumatoid factor (RF)(85%)/ anti-cyclic citrullinated peptide antibodies (ACCP)(80%). The study did not include RA pts with CHF and clinically overt cardiovascular disease (CVD). Twenty nine RA pts received TCZ(8mg/kg) every 4 weeks: 61% received TCZ in combination with methotrexate (MTX), 35% - with low-dose glucocorticoids (GCs). Thirty one RA pts were prescribed oral TOFA at 5 mg BID with dose escalation to 10 mg BID in 8 (26%)pts. TOFA was used in combination with MTX in 90% pts, with GCs – in 29% pts. Pts treated with TCZ and TOFA were comparable in terms of age, sex, body mass index. RA activity rates (DAS28, SDAI, ESR, CRP) were higher in pts on TCZ -therapy compared with pts treated with TOFA. Echocardiography data and NT-proBNP levels using electrochemiluminescence method Elecsys proBNP II (Roche Diagnostics, Switzerland) were obtained at baseline and after 12m. Results: Significant positive changes in major disease activity, clinical and laboratory parameters were found in RA pts after 12 m of TCZ infusion and TOFA intake: remission (DAS28&lt;2,6) was achieved in 54% and 39% pts, low activity levels (DAS28&lt;3,2) – in 46% and 51% pts, respectively. The NT-proBNP levels were significantly higher in RA pts than in the control group (median 69,1 (37,9;105,8) pg/mL vs 55,3 (36,6;67,3) pg/mL, p &lt;0.05). Six pts (10%) (three in each pts group) had NT-proBNP levels over 125pg/ml, but were asymptomatic and had unremarkable echocardiography. There was a good correlation between NT-proBNP level at baseline with age (r=0,55, p &lt;0,001), SDAI (r=0,5, h=0,01), ACCP (r=0,23, p =0,01). Decrease of median NT-proBNP levels was documented after 12m of TCZ therapy (81,5[43,0;102,0]vs41,6[25,4;64,2]pg/ml ( p &lt;0,01) and after 12m TOFA therapy (66,1[30,5;105,0]vs16,8 [5,0;81,0]pg/ml, p= 0,001). After 12m of TCZ correlations of ΔNT-proBNP were established with ΔESR (R=0,43;p&lt;0,05], ΔСRP (R=0,46;p&lt;0,05], ΔEe left ventricle (LV) (r=0,88,p=0,03). In the group of pts treated with TOFA ΔNT-proBNP level significantly correlated with the percentage change in DAS 28 (r=0,41,p=0,038), there was no direct correlation with changes in the parameters of the LV diastolic function. Conclusion: TCZ and TOFA treatment for 12 m reduced NT-proBNP levels in RA pts without clinically manifest CVD and CHF. Falling NT-proBNP concentrations are associated with positive dynamics of RA activity (DAS 28) and inflammatory markers (CRP, ESR), therefore allowing to suggest that increased NT-proBNP levels should be considered as a component of disease activity. Correlation between ΔNT-proBNP and ΔEeLF may be indicative as possible impact of these biomarkers on the LV diastolic function’s development in RA pts. Disclosure of Interests: None declared