Effect of IL-6 receptor blockade on high-sensitivity troponin T and NT-proBNP in rheumatoid arthritis

被引:17
作者
Welsh, Paul [1 ]
Tuckwell, Katie [2 ]
McInnes, Iain B. [3 ]
Sattar, Naveed [1 ]
机构
[1] Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland
[2] Roche Prod Ltd, Welwyn Garden City, Herts, England
[3] Univ Glasgow, Inst Infect Immun & Inflammat, Glasgow, Lanark, Scotland
关键词
IL-6; Tocilizumab; Troponin; Natriuretic peptide; Rheumatoid arthritis; CORONARY-HEART-DISEASE; TUMOR-NECROSIS-FACTOR; HIGH BNP LEVELS; CARDIOVASCULAR EVENTS; NATRIURETIC PEPTIDE; SKELETAL-MUSCLE; RISK; METAANALYSIS; INFLAMMATION; PREDICTION;
D O I
10.1016/j.atherosclerosis.2016.10.016
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background and aims: Observational associations between inflammation and cardiovascular disease are interesting, but randomised experimental data are lacking. We investigated the effect of the IL-6 receptor blocker tocilizumab on N terminal pro B type natriuretic peptide (NT-proBNP) and high sensitivity troponin T (hsTnT) in rheumatoid arthritis (RA) patients. Methods: A post-hoc study was performed in a subset of patients with moderate to severe RA participating in a randomised controlled trial. The effect of tocilizumab on cardiac biomarkers was determined using stored serum (baseline and 24 weeks) in recipients of tocilizumab (8 mg/kg every 4 weeks plus DMARDs; n = 225) or placebo (every 4 weeks plus DMARDs; n = 132). Results: Median NT-proBNP and hsTnT concentrations at baseline were 100 pg/ml and 5.7 pg/ml, respectively. NT-proBNP decreased in both study arms (median at 24 weeks 77 pg/ml in the placebo arm, 79 pg/ml in the tocilizumab arm; p < 0.001 for the decrease in both arms), and decreased to a similar extent comparing study arms (tocilizumab effect: -5.5%, p = 0.55). hsTnT also decreased in both study arms (median at 24 weeks 3.1 pg/ml in the placebo arm, 4.4 pg/ml in the tocilizumab arm; p < 0.001 for the decrease in both arms). The extent of the reduction in hsTnT was greater in the placebo group (tocilizumab effect: +23.3%, p = 0.002). Change in NT-proBNP, but not hsTnT, correlated modestly with change in CRP (r = 0.17, p = 0.013). Conclusions: These data argue against a rapid preferential benefit of IL-6 blockade on these specific surrogate markers of cardiovascular risk, but may be consistent with a general cardiovascular benefit of improved RA treatment. (C) 2016 The Authors. Published by Elsevier Ireland Ltd.
引用
收藏
页码:167 / 171
页数:5
相关论文
共 26 条
  • [11] C-Reactive Protein, Fibrinogen, and Cardiovascular Disease Prediction
    Kaptoge, Stephen
    Di Angelantonio, Emanuele
    Pennells, Lisa
    Wood, Angela M.
    White, Ian R.
    Gao, Pei
    Walker, Matthew
    Thompson, Alexander
    Sarwar, Nadeem
    Caslake, Muriel
    Butterworth, Adam S.
    Amouyel, Philippe
    Assmann, Gerd
    Bakker, Stephan J. L.
    Barr, Elizabeth L. M.
    Barrett-Connor, Elizabeth
    Benjamin, Emelia J.
    Bjorkelund, Cecilia
    Brenner, Hermann
    Brunner, Eric
    Clarke, Robert
    Cooper, Jackie A.
    Cremer, Peter
    Cushman, Mary
    Dagenais, Gilles R.
    D'Agostino, Ralph B., Sr.
    Dankner, Rachel
    Davey-Smith, George
    Deeg, Dorly
    Dekker, Jacqueline M.
    Engstrom, Gunnar
    Folsom, Aaron R.
    Fowkes, F. Gerry R.
    Gallacher, John
    Gaziano, J. Michael
    Giampaoli, Simona
    Gillum, Richard F.
    Hofman, Albert
    Howard, Barbara V.
    Ingelsson, Erik
    Iso, Hiroyasu
    Jorgensen, Torben
    Kiechl, Stefan
    Kitamura, Akihiko
    Kiyohara, Yutaka
    Koenig, Wolfgang
    Kromhout, Daan
    Kuller, Lewis H.
    Lawlor, Debbie A.
    Meade, Tom W.
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2012, 367 (14) : 1310 - 1320
  • [12] Effect of a single dose of the interleukin-6 receptor antagonist tocilizumab on inflammation and troponin T release in patients with non-STelevation myocardial infarction: a double-blind, randomized, placebo-controlled phase 2 trial+
    Kleveland, Ola
    Kunszt, Gabor
    Bratlie, Marte
    Ueland, Thor
    Broch, Kaspar
    Holte, Espen
    Michelsen, Annika E.
    Bendz, Bjorn
    Amundsen, Brage H.
    Espevik, Terje
    Aakhus, Svend
    Damas, Jan Kristian
    Aukrust, Pal
    Wiseth, Rune
    Gullestad, Lars
    [J]. EUROPEAN HEART JOURNAL, 2016, 37 (30) : 2406 - 2413
  • [13] Effect of interleukin-6 receptor blockade on surrogates of vascular risk in rheumatoid arthritis: MEASURE, a randomised, placebo-controlled study
    McInnes, Iain B.
    Thompson, Liz
    Giles, Jon T.
    Bathon, Joan M.
    Salmon, Jane E.
    Beaulieu, Andre D.
    Codding, Christine E.
    Carlson, Timothy H.
    Delles, Christian
    Lee, Janet S.
    Sattar, Naveed
    [J]. ANNALS OF THE RHEUMATIC DISEASES, 2015, 74 (04) : 694 - 702
  • [14] Impact of disease activity and treatment of comorbidities on the risk of myocardial infarction in rheumatoid arthritis
    Meissner, Yvette
    Zink, Angela
    Kekow, Joern
    Rockwitz, Karin
    Liebhaber, Anke
    Zinke, Silke
    Gerhold, Kerstin
    Richter, Adrian
    Listing, Joachim
    Strangfeld, Anja
    [J]. ARTHRITIS RESEARCH & THERAPY, 2016, 18
  • [15] High BNP levels in rheumatoid arthritis may be related with right ventricular functions
    Ozturk, Cengiz
    Balta, Sevket
    Demirkol, Sait
    Ozturk, Ahmet
    Celik, Turgay
    Iyisoy, Atila
    [J]. INTERNATIONAL JOURNAL OF CARDIOLOGY, 2014, 174 (01) : 149 - 150
  • [16] Tumour necrosis factor a blockade reduces circulating N-terminal pro-brain natriuretic peptide levels in patients with active rheumatoid arthritis: results from a prospective cohort study
    Peters, Mike J. L.
    Welsh, Paul
    McInnes, Iain B.
    Wolbink, Gertjan
    Dijkmans, Ben A. C.
    Sattar, Naveed
    Nurmohamed, Michael T.
    [J]. ANNALS OF THE RHEUMATIC DISEASES, 2010, 69 (07) : 1281 - 1285
  • [17] Ridker Paul M, 2013, Trans Am Clin Climatol Assoc, V124, P174
  • [18] Elevation of Cardiac Troponin T, But Not Cardiac Troponin I, in Patients With Neuromuscular Diseases
    Rittoo, Dylmitr
    Jones, Alan
    Lecky, Bryan
    Neithercut, Duncan
    [J]. JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2014, 63 (22) : 2411 - 2420
  • [19] The effects of tumour necrosis factor inhibitors, methotrexate, non-steroidal anti-inflammatory drugs and corticosteroids on cardiovascular events in rheumatoid arthritis, psoriasis and psoriatic arthritis: a systematic review and meta-analysis
    Roubille, Camille
    Richer, Vincent
    Starnino, Tara
    McCourt, Collette
    McFarlane, Alexandra
    Fleming, Patrick
    Siu, Stephanie
    Kraft, John
    Lynde, Charles
    Pope, Janet
    Gulliver, Wayne
    Keeling, Stephanie
    Dutz, Jan
    Bessette, Louis
    Bissonnette, Robert
    Haraoui, Boulos
    [J]. ANNALS OF THE RHEUMATIC DISEASES, 2015, 74 (03) : 480 - 489
  • [20] Association Between Biologic Therapies for Chronic Plaque Psoriasis and Cardiovascular Events A Meta-analysis of Randomized Controlled Trials
    Ryan, Caitriona
    Leonardi, Craig L.
    Krueger, James G.
    Kimball, Alexa B.
    Strober, Bruce E.
    Gordon, Kenneth B.
    Langley, Richard G.
    de Lemos, James A.
    Daoud, Yahya
    Blankenship, Derek
    Kazi, Salahuddin
    Kaplan, Dan H.
    Friedewald, Vincent E.
    Menter, Alan
    [J]. JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2011, 306 (08): : 864 - 871