LAUSR

Background The amino-terminal fragment of the B-type natriuretic peptide prohormone (NT-proBNP) is a marker for functional cardiac impairment and is increased in heart disease with or without symptoms of congestive heart failure (CHF)1. Objectives To prospectively investigate the effect of tofacitinib (TOFA) on the levels of NT-proBNP, as a predictor of CHF in patients (pt) with active rheumatoid arthritis (RA). Methods Twenty six RA pt (median age 54 [40;62] years, 81% female, disease duration 44[24;63,0] month (m), moderate to high activity (DAS28-5.1[4.6;6.1], SDAI–27(22;35)), positive for ACCP (73%)/RF (77%), who were non-responders to MTX at least 15 mg/week and/or other synthetic DMARDs and bDMARDs) free of clinical overt cardiovascular disease were treated with TOFA and followed for 12 m. TOFA therapy was started in all pt in dose 5 mg BID per os with dose escalation to 10 mg BID in 8 (31%) pt. TOFA used in combination with MTX in 24 (92%) pt, leflunomide in 1 (4%). Low-dose oral corticosteroids (<10 mg/day prednisone or equivalent) were received by 9 (35%) pt. Remission was achieved in 38,5% pt (DAS28), 38,5% (SDAI). Cardiovascular risk factors (CVRF) and the NT-proBNP levels were measured at baseline and after 12m. At baseline the most of pt had multiple CVRF and subclinical organ damage. Cardioprotective therapy received 16 (57%) pt (β-AB–7, ARA/ACE inhibitors–11, statins–11, dihydropyridine CCB-7). Twenty controls matched for CVRF were included for comparison of normal NT-proBNP levels with those of RA pt. Results The NT-proBNP level was significantly higher in RA pt than in the control group (median 62.2(26.9-101.7) pg/mL vs 44.0 (34.0-54.3) pg/mL, p<0.05). At baseline NT-proBNP level was higher in female than in male (p=0,019). Its concentration correlated with DAS28 (r=0,41,p=0,036). Three pt (11,5%) had NT-proBNP level over 125 pg/mL. All RA pt with a NT-proBNP level over 125 pg/mL were asymptomatic and exhibited normal echocardiography. Median DAS28 and SDAI were significantly reduced following TOFA treatment (from 5.1 to 2.9, p < 0.001 and from 26.8 to 4.7, p < 0.001, respectively). During follow-up, no RA pt exhibited a cardiovascular event or CHF. NT-proBNP levels decreased by 63% over the 12-m of TOFA treatment (from 62.16 pg/mL to 14.8 pg/mL, p= 0.011). The incidence rate of arterial hypertention (58%vs65%), overweight (62%vs62%), abdominal obesity (58%vs62%), smokers (27%vs27%), menopausal status (52%vs52%), DM type 2 (7%vs7%), mSCORE≥5% (23%vs27%), subclinical carotid atherosclerosis (58%vs58%) did not change significantly. An increase in body mass index (BMI) was observed from 26.5[22.9;29.0] to 26.9[24.0;30.1],p<0.001 and in HDL level from 1.37[1.06;1.87] to 1.90[1.29;2.16],p<0.01. The percentage change in the NT-proBNP level significantly correlated with the percentage change in the BMI (r=0,6,p=0,007), DAS 28 (r = 0.41, p = 0.038) SDAI (r = 0.51, p = 0.009). Changes in NT-proBNP levels in RA pt with remission was greater than that observed in pt who didn’t achieve remission (-87% vs -26%, p=0,005). The percentage change in the NT-proBNP level was not correlated with the percentage change in other CVRF. Conclusion TOFA decreased the NT-proBNP level in patients with RA without clinical overt cardiovascular disease and CHF. TOFA may have a cardioprotective effect in those with active RA. Reference [1] Breunig M., Kleinert S., Lehmann S. et al. Simple screening tools predict death and cardiovascular events in patients with rheumatic disease. Scand J Rheumatol2018;47(2):102-109. doi: 10.1080/03009742.2017.1337924. Disclosure of Interests Diana Novikova: None declared, Irina Kirillova: None declared, Eugenia Markelova: None declared, Helen Udachkina: None declared, Helen Gerasimova: None declared, Helen Luchihina Speakers bureau: Pfizer, Abbvie, Biocad, Dmitriy Karateev: None declared, Natalia Demidova: None declared, Anna Misiyuk: None declared, Maria Cherkasova: None declared, Tatiana Popkova: None declared