P4434The first report of significantly improvement of NT-proBNP level in rheumatoid arthritis patients treated with tofacitinib during 12-month follow-up
Authors: Novikova D , Kirillova I , Markelova E , Udachkina H , Gerasimova H , Popkova T , Demidova N , Misiyuk A , Cherkasova M 
Published: October 2019

Abstract

Objectives
To prospectively investigate the effect of tofacitinib (TOFA), the first oral reversible inhibitor of JAK approved for RA treatment, on the levels of NT-proBNP, as a predictor of congestive heart failure (CHF) in patients (pt) with active 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 (SDAI–27 (22; 35)), positive for ACCP (73%)/RF (77%), who were non-responders to methotrexate (MTX) at least 15 mg/week and other synthetic DMARDs) 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% (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 (beta-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.

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). All 3 (11,5%) RA pt with a NT-proBNP level over 125 pg/mL were asymptomatic and exhibited normal echocardiography. Median SDAI were significantly reduced following TOFA treatment (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% vs 65%), overweight (62% vs 62%), abdominal obesity (58% vs 62%), smokers (27% vs 27%), menopausal status (52% vs 52%), DM type 2 (7% vs 7%), mSCORE≥5% (23% vs 27%), subclinical carotid atherosclerosis (58% vs 58%) 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), 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.