Session Type: Abstract Submissions (ACR)
Patients with rheumatoid arthritis (RA) have a 1.5–2.0 fold higher risk of developing congestive heart failure (CHF) than the general population. Small increases in N-terminal pro-brain natriuretic peptide (NT-proBNP) levels predict left ventricular (LV) dysfunction and cardiac stress. NT-pro BNP is also associated with pro-inflammatory cytokines such as interleukin 6 (IL-6). Data relating to the effects of IL-6 blocking agents (tocilizumab, TCZ) on circulating NT-proBNP levels in patients with active RA are lacking but may be informative. We therefore investigated the effects of TCZ therapy on the NT-proBNP levels in RA patients without cardiac symptoms before and after 24 weeks of treatment.
RA patients with active disease with an inadequate clinical response to non biologic DMARDs and non-RA healthy control were enrolled. Exclusion criteria were diabetes, previous cardiovascular events, cardiopathy, hypertension and renal disease. The RA patients received TCZ once a month for 24 weeks. Serum NT-pro BNP levels were measured at baseline and week 24. Clinical and biological monitoring was performed at baseline and 24 weeks after the start of TCZ treatment. We explored the associations between NT-pro BNP and the RA disease activity score for Simple Disease Activity Index (SDAI) scores. The anti-citrullinated protein antibody (ACPA) titre was divided into high and low levels using a cut-off of 30 units/mL. Fisher test and multivariable linear regression analyses were performed to identify the correlations.
90 patients (mean age, 56.4 ± 10.4 years; 85% female) and a matched 30-patient control group (mean age 55.6±3.4 years; 86% female) were enrolled. The SDAI at baseline was 22.5 ± 12.7. The 24-week SDAI scores were significantly lower than those at baseline (p = 0.03). The NT-proBNP levels at baseline were significantly higher than control group (p=0.04). The median (interquartile range) levels of the NT-proBNP significantly decreased from baseline (121.78 [52.81–230.24] pg/mL) to 24 weeks (57.13 [29.50–128.67] pg/mL, p = 0.004) following TCZ treatment. NT-proBNP levels in the high ACPA group tended to be higher than the low ACPA group (p = 0.07). The change in NT-proBNP levels was significantly correlated with the change in the SDAI score (r =0.455, p = 0.003). After adjustment for age, gender, erythrocyte sedimentation rate (ESR), and RA duration, the association between the change in NT-proBNP levels and the change in SDAI remained significant (p = 0.023).
This is the first study to report the effect of IL-6 blocking agent on circulating NT-proBNP levels in patients with active RA. Our results suggest that blocking IL-6 in patients with RA without cardiac symptoms does not increase but rather decreases circulating NT-proBNP levels by around 52%, which was also related to a reduction in disease activity. Our data also suggest that RA-specific autoimmunity against citrullinated proteins might relate to subclinical cardiac stress. TCZ treatment may influence the presence of subclinical left ventricular dysfunction or cardiac stress which may progress to overt CHF.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/il-6-blockade-reduces-circulating-n-terminal-pro-brain-natriuretic-peptide-levels-in-patients-with-active-rheumatoid-arthritis/