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AB0321 IL-6 Blockade Reduces Circulating N-Terminal Pro-Brain Natriuretic Peptide Levels in Patients with Active Rheumatoid Arthritis
  1. H. Inomata1,
  2. H. Kobayashi1,2,
  3. Y. Kobayashi3,
  4. N. Ikumi1,
  5. I. Yokoe1,
  6. Y. Nagasawa1,
  7. K. Sugiyama1,
  8. T. Nozaki1,
  9. H. Shiraiwa1,
  10. N. Kitamura1,
  11. M. Iwata1,
  12. M. Takei1
  1. 1Division of Hematology and Rheumatology, Nihon University School of Medicine
  2. 2Rheumatology, Itabashi Chuo Medical Center, Tokyo
  3. 3Radiology, St. Marianna University School of Medicine, Kawasaki, Japan

Abstract

Background Patients with rheumatoid arthritis (RA) have a 1.5–2.0 fold higher risk of developing congestive heart failure than the general population. Small increases in N-terminal pro-brain natriuretic peptide (NT-proBNP) levels predict left ventricular (LV) dysfunction, and the LV myocardium is the primary site of NT-proBNP production. Data relating to the effects of interleukin (IL)-6 blocking agents on circulating NT-proBNP levels in patients with active RA are lacking but may be informative. To our knowledge, there are no published reports regarding the effect of tocilizumab (TCZ) treatment on NT-proBNP levels.

Objectives To test the hypothesis anti-IL-6 therapy might reduce circulating NT-proBNP levels.

Methods RA patients with active disease without a clinical diagnosis of cardiovascular disease (CVD) and with an inadequate clinical response to DMARDs were enrolled. The patients received TCZ once a month after 24 weeks. Serum NT-pro BNP levels were measured on the Cobas 6000 modular analyzer simultaneously on stored baseline and 24-week samples, and NT-pro-BNP levels ≥100 pg/mL were considered elevated. We explored the associations between NT-pro BNP and the RA disease activity score for 28 joints: erythrocyte sedimentation rate (DAS28-ESR) and 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. Correlations between the biomarkers and changes in circulating NT-proBNP levels were evaluated using the Spearman rank test, and multivariable linear regression analyses of the correlates were performed.

Results Sixty RA patients (mean age, 60.4±10.4 years; 75% female) were enrolled. The DAS28-ESR and SDAI at baseline were 4.57±1.35 and 22.5±12.7, respectively. The 24-week DAS28-ESR and SDAI scores were significantly lower than those at baseline (p=0.04, p=0.03, respectively). The NT-proBNP levels at baseline were approximately 31% higher than normal levels, and the median (interquartile range) levels significantly decreased from baseline (131.78 [52.81–230.24] pg/mL) to 24 weeks (57.13 [29.50–128.67] pg/mL, p=0.004) following TCZ treatment. The change in NT-proBNP levels was significantly correlated with the change in the SDAI score and swollen joints count (SJC) (r =0.455, p=0.003, r =0.395, p=0.004, respectively). The baseline NT-proBNP levels in the high ACPA group tended to be higher than in the low ACPA group (p=0.07). After adjustment for age, gender, ESR, and RA duration, the association between the change in NT-proBNP levels and the change in SJC remained significant (p=0.023).

Conclusions The NT-proBNP level was higher than normal in patients with active RA without CVD; this may indicate subclinical left ventricular dysfunction. Furthermore, our results indicate the NT-proBNP levels decreased by approximately 38% with TCZ treatment, which was related to a reduction in disease activity. Therefore, TCZ treatment may directly influence the anti-inflammatory effect of IL-6 on the myocardium.

Disclosure of Interest None declared

DOI 10.1136/annrheumdis-2014-eular.2189

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