P129. Elevated NTproBNP in patients with Crohn's disease
J.‑F. Colombel1, G. Van Assche2, F. Cataldi3, K.J. Gorelick4, G.E. Cooke5, J. Potts4, S. Rivers4, B. Jin3, G. Comer4
1Centre Hospitalier Universitaire de Lille, Hôpital Claude Huriez, Lille, France; 2University Hospital Gasthuisberg, Dept. of Gastroenterology, Leuven, Belgium; 3Pfizer, GI, Biotherapeutics Clinical Programs, Boston, United States; 4Pfizer Inc., Bio-therapeutics, Collegeville, United States; 5EPI, Inc, Cardology, Columbus, OH, United Kingdom
Background: NTproBNP is the inactive amino-terminal (NT) fragment of pro-brain natriuretic peptide (proBNP) It has been shown to be a sensitive and specific indicator of heart failure when dyspnea is present (Januzzi JL et al. Am J Cardiol. 2005;95:9480). Patients with rheumatoid arthritis may have elevated NTproBNP in the absence of clinical heart failure (Armstrong et al. Ulster Med J. 2010;79:82). PF-00547649 is a fully human monoclonal antibody to MAdCAM in development to treat moderate to severe Crohn's disease (CD). In an ongoing Phase 2 clinical efficacy trial (OPERA: NCT01276509) subjects with heart failure are excluded based on history & physical or elevated NTproBNP. We here report the first data regarding measurement of NTproBNP in patients with CD included this trial.
Methods: Subjects with moderate to severely active Crohn's disease undergo screening and on-treatment testing for NTproBNP and hsCRP. If NTproBNP is elevated (>124 pg/mL) subjects are required to undergo echocardiography and cardiology consultation to determine if heart failure is present. Subjects without heart failure are permitted to enroll in the study.
Results: To date, 12 subjects have been evaluated. The observed pre-treatment NTproBNP values ranged from 23 to 535 pg/mL with the median of 91 pg/mL, and the observed pre-treatment hsCRP values ranged from 1.79 to 220.26 mg/dl with the median 18.54 mg/dl. 50% (6/12) of subjects had pre-treatment values of NTproBNP >124 pg/mL. Four subjects underwent echocardiography and cardiology consultation. Only 1 subject had an abnormal echocardiogram (Ejection Fraction 2025%). This subject also had the highest NTproBNP (535 pg/mL) and detailed history noted dyspnea and orthopnea. The other 3 had no abnormality and were enrolled in the study. In 1 subject a minimal pre-treatment NTproBNP elevation returned to normal, and the subject was enrolled in the study without further testing. No subject with normal pre-treatment values developed de novo elevation of NTproBNP. Three of 4 subjects enrolled with elevated pre-treatment NTproBNP returned to normal values during treatment. Significant correlation was observed between NTproBNP and hsCRP (p-value <0.01).
Conclusions: This is the first report of elevated NTproBNP in patients with CD that occurred in the absence of ventricular dysfunction in most patients. Further studies are needed to assess the significance of this finding and the value of NTproBNP as a biomarker of inflammation in CD.