Skip to main content

Advertisement

SpringerLink
Log in

Biologic drugs and arrhythmic risk in chronic inflammatory arthritis: the good and the bad

  • Therapeutic Aspects in Autoimmunity
  • Published:
Immunologic Research Aims and scope Submit manuscript

Abstract

Increasing evidence indicates that patients with chronic inflammatory arthritis (CIA), including rheumatoid arthritis and spondyloarthropathies, have an increased risk of arrhythmic events, significantly contributing to the higher cardiovascular disease (CVD) morbidity and mortality observed in these subjects compared to the general population. Although the mechanisms accounting for such an arrhythmogenic substrate are not fully understood, the main role is probably played by chronic systemic inflammation, able to accelerate the development of structural CVD, as well as to directly affect cardiac electrophysiology. In the past decade, biologic therapies have revolutionized the treatment of CIA by highly enhancing the probability to effectively control disease activity and its systemic consequences, including cardiovascular involvement. Accordingly, accumulating data demonstrated that by potently inhibiting systemic inflammation, biologic drugs can reduce CVD progression and ameliorate arrhythmic risk parameters, with a putative beneficial impact on arrhythmia incidence. Nevertheless, a significant number of reports from clinical trials and postmarketing experience suggest that some of these medications, particularly TNF inhibitor monoclonal antibodies and rituximab, may in some circumstances precipitate arrhythmia occurrence, probably by acutely amplifying myocardial electric instability intrinsically associated with these diseases. In this review, we analyze the intricate link between biologic drugs and arrhythmias in CIA in the effort to identify which factors are involved in the fine-tuning of antiarrhythmic/pro-arrhythmic balance, and understand how this knowledge should be translated in the clinical practice to obtain the most favorable benefit-to-risk profile when biologic drugs are used in these patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Hadam J, Aoun E, Clarke K, Wasko MC. Managing risks of TNF inhibitors: an update for the internist. Cleve Clin J Med. 2014;81:115–27.

    Article  PubMed  Google Scholar 

  2. Woodrick RS, Ruderman EM. Safety of biologic therapy in rheumatoid arthritis. Nat Rev Rheumatol. 2011;7:639–52.

    Article  CAS  PubMed  Google Scholar 

  3. Johnsson HJ, McInnes IB. Interleukin-12 and interleukin-23 inhibition in psoriatic arthritis. Clin Exp Rheumatol. 2015;33:S115–8.

    PubMed  Google Scholar 

  4. Peters MJL, Symmons DPM, McCarey D, Dijkmans BAC, Nicola P, Kvien TK, McInnes IB, Haentzschel H, Gonzalez-Gay MA, Provan S, Semb A. EULAR evidence-based recommendations for cardiovascular risk management in patients with rheumatoid arthritis and other forms of inflammatory arthritis. Ann Rheum Dis. 2010;69:325–31.

    Article  CAS  PubMed  Google Scholar 

  5. John H, Kitas G. Inflammatory arthritis as a novel risk factor for cardiovascular disease. Eur J Intern Med. 2012;23:575–9.

    Article  PubMed  Google Scholar 

  6. Mantel Ä, Holmqvist M, Jernberg T, Wållberg-Jonsson S, Askling J. Rheumatoid arthritis is associated with a more severe presentation of acute coronary syndrome and worse short-term outcome. Eur Heart J. 2015;36:3413–22.

    Article  PubMed  Google Scholar 

  7. Maradit-Kremers H, Crowson CS, Nicola PJ, Ballman KV, Ballman KV, Roger VL, Jacobsen SJ, Gabriel SE. Increased unrecognized coronary heart disease and sudden death in rheumatoid arthritis: a population-based cohort study. Arthritis Rheum. 2005;52:402–11.

    Article  PubMed  Google Scholar 

  8. Ungprasert P, Srivali N, Kittanamongkolchai W. Risk of incident atrial fibrillation in patients with rheumatoid arthritis: a systematic review and meta-analysis. Int J Rheum Dis. 2015. doi:10.1111/1756-185X.12820.

    Google Scholar 

  9. Lazzerini PE, Capecchi PL, Laghi-Pasini F. Systemic inflammation and arrhythmic risk: lessons from rheumatoid arthritis. Eur Heart J. 2016. doi:10.1093/eurheartj/ehw208.

  10. Huikuri HV, Castellanos A, Myerburg RJ. Sudden death due to cardiac arrhythmias. N Engl J Med. 2001;345:1473–82.

    Article  CAS  PubMed  Google Scholar 

  11. Lazzerini PE, Capecchi PL, Acampa M, Galeazzi M, Laghi-Pasini F. Arrhythmic risk in rheumatoid arthritis: the driving role of systemic inflammation. Autoimmun Rev. 2014;13:936–44.

    Article  PubMed  Google Scholar 

  12. Panoulas VF, Toms TE, Douglas KM, Sandoo A, Metsios GS, Stavropoulos-Kalinoglou A, Kitas GD. Prolonged QTc interval predicts all-cause mortality in patients with rheumatoid arthritis: an association driven by high inflammatory burden. Rheumatology. 2014;53:131–7.

    Article  PubMed  Google Scholar 

  13. Chauhan K, Ackerman M, Crowson CS, Matteson EL, Gabriel SE. Population-based study of QT interval prolongation in patients with rheumatoid arthritis. Clin Exp Rheumatol. 2015;33:84–9.

    PubMed  PubMed Central  Google Scholar 

  14. Peters MJ, van der Horst-Bruinsma IE, Dijkmans BA, Nurmohamed MT. Cardiovascular risk profile of patients with spondyloarthropathies, particularly ankylosing spondylitis and psoriatic arthritis. Semin Arthritis Rheum. 2004;34(585–5):92.

    Google Scholar 

  15. Jamnitski A, Symmons D, Peters MJ, Sattar N, McInnes I, Nurmohamed MT. Cardiovascular comorbidities in patients with psoriatic arthritis: a systematic review. Ann Rheum Dis. 2013;72:211–6.

    Article  PubMed  Google Scholar 

  16. Szabo SM, Levy AR, Rao SR, Kirbach SE, Lacaille D, Cifaldi M, Maksymowych WP. Increased risk of cardiovascular and cerebrovascular diseases in individuals with ankylosing spondylitis: a population-based study. Arthritis Rheum. 2011;63:3294–304.

    Article  PubMed  Google Scholar 

  17. Mathieu S, Gossec L, Dougados M, Soubrier M. Cardiovascular profile in ankylosing spondylitis: a systematic review and meta-analysis. Arthritis Care Res. 2011;63:557–63.

    Article  Google Scholar 

  18. Chiu HY, Chang WL, Huang WF, Wen YW, Tsai YW, Tsai TF. Increased risk of arrhythmia in patients with psoriatic disease: a nationwide population-based matched cohort study. J Am Acad Dermatol. 2015;73:429–38.

    Article  PubMed  Google Scholar 

  19. Ahlehoff O, Gislason GH, Jørgensen CH, Lindhardsen J, Charlot M, Olesen JB, Abildstrøm SZ, Skov L, Torp-Pedersen C, Hansen PR. Psoriasis and risk of atrial fibrillation and ischaemic stroke: a Danish Nationwide cohort study. Eur Heart J. 2012;33:2054–64.

    Article  PubMed  Google Scholar 

  20. Keller JJ, Hsu JL, Lin SM, Chou CC, Wang LH, Wang J, Bai CH, Chiou HY. Increased risk of stroke among patients with ankylosing spondylitis: a population-based matched-cohort study. Rheumatol Int. 2014;34:255–63.

    Article  PubMed  Google Scholar 

  21. Lazzerini PE, Acampa M, Capecchi PL, Hammoud M, Maffei S, Bisogno S, Barreca C, Galeazzi M, Laghi-Pasini F. Association between high sensitivity C-reactive protein, heart rate variability and corrected QT interval in patients with chronic inflammatory arthritis. Eur J Intern Med. 2013;24:368–74.

    Article  CAS  PubMed  Google Scholar 

  22. Lazzerini PE, Capecchi PL, Laghi-Pasini F. Long QT syndrome: an emerging role for inflammation and immunity. Front Cardiovasc Med. 2015;2:26.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Simsek H, Sahin M, Akyol A, Akdag S, Ozkol HU, Gumrukcuoglu HA, Gunes Y. Increased risk of atrial and ventricular arrhythmia in long-lasting psoriasis patients. Sci World J. 2013;2013:901215.

    Article  Google Scholar 

  24. Bacaksiz A, Erdogan E, Tasal A, Vatankulu MA, Kul S, Sevgili E, Ertas G, Dizman D, Onsun N, Uysal O. Electrocardiographic P-wave characteristics in patients with psoriasis vulgaris. Ups J Med Sci. 2013;118:35–41.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Borman P, Gokoglu F, Kocaoglu S, Yorgancioglu ZR. The autonomic dysfunction in patients with ankylosing spondylitis: a clinical and electrophysiological study. Clin Rheumatol. 2008;27:1267–73.

    Article  PubMed  Google Scholar 

  26. Acar G, Yorgun H, Inci MF, Akkoyun M, Bakan B, Nacar AB, Dirnak I, Cetin GY, Bozoglan O. Evaluation of Tp-e interval and Tp-e/QT ratio in patients with ankylosing spondylitis. Mod Rheumatol. 2014;24:327–30.

    Article  PubMed  Google Scholar 

  27. Libby P. Role of inflammation in atherosclerosis associated with rheumatoid arthritis. Am J Med. 2008;121:S21–31.

    Article  CAS  PubMed  Google Scholar 

  28. Rudominer RL, Roman MJ, Devereux RB, Paget SA, Schwartz JE, Lockshin MD, Crow MK, Sammaritano L, Levine DM, Salmon JE. Independent association of rheumatoid arthritis with increased left ventricular mass but not with reduced ejection fraction. Arthritis Rheum. 2009;60:22–9.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Liang KP, Myasoedova E, Crowson CS, Davis JM, Roger VL, Karon BL, Borgeson DD, Therneau TM, Rodeheffer RJ, Gabriel SE. Increased prevalence of diastolic dysfunction in rheumatoid arthritis. Ann Rheum Dis. 2010;69:1665–70.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Kobayashi Y, Giles JT, Hirano M, Yokoe I, Nakajima Y, Bathon JM, Lima JA, Kobayashi H. Assessment of myocardial abnormalities in rheumatoid arthritis using a comprehensive cardiac magnetic resonance approach: a pilot study. Arthritis Res Ther. 2010;12:R171.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Gabriel SE. Cardiovascular morbidity and mortality in rheumatoid arthritis. Am J Med. 2008;121:S9–14.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Han C, Robinson DW Jr, Hackett MV, Paramore LC, Fraeman KH, Bala MV. Cardiovascular disease and risk factors in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. J Rheumatol. 2006;33:2167–72.

    PubMed  Google Scholar 

  33. Aviña-Zubieta JA, Choi HK, Sadatsafavi M, Etminan M, Esdaile JM, Lacaille D. Risk of cardiovascular mortality in patients with rheumatoid arthritis: a meta-analysis of observational studies. Arthritis Rheum. 2008;59:1690–7.

    Article  PubMed  Google Scholar 

  34. Nicola PJ, Crowson CS, Maradit-Kremers H, Ballman KV, Roger VL, Jacobsen SJ, Gabriel SE. Contribution of congestive heart failure and ischemic heart disease to excess mortality in rheumatoid arthritis. Arthritis Rheum. 2006;54:60–7.

    Article  PubMed  Google Scholar 

  35. Tomaselli GF, Zipes DP. What causes sudden death in heart failure? Circ Res. 2004;95:754–63.

    Article  CAS  PubMed  Google Scholar 

  36. Di Diego JM, Antzelevitch C. Ischemic ventricular arrhythmias: experimental models and their clinical relevance. Heart Rhythm. 2011;8:1963–8.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Lubitz SA, Benjamin EJ, Ellinor PT. Atrial fibrillation in congestive heart failure. Heart Fail Clin. 2010;6:187–200.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Nattel S, Maguy A, Le Bouter S, Yeh YH. Arrhythmogenic ion-channel remodeling in the heart: heart failure, myocardial infarction, and atrial fibrillation. Physiol Rev. 2007;87:425–56.

    Article  CAS  PubMed  Google Scholar 

  39. Nattel S, Burstein B, Dobrev D. Atrial remodeling and atrial fibrillation: mechanisms and implications. Circ Arrhythm Electrophysiol. 2008;1:62–73.

    Article  PubMed  Google Scholar 

  40. Elenkov IJ, Wilder RL, Chrousos GP, Vizi S. The sympathetic nerve: an integrative interface between two supersystems: the brain and the immune system. Pharmacol Rev. 2000;52:595–638.

    CAS  PubMed  Google Scholar 

  41. Tracey KJ. The inflammatory reflex. Nature. 2002;420:853–9.

    Article  CAS  PubMed  Google Scholar 

  42. Martelli D, Yao ST, McKinley MJ, McAllen RM. Reflex control of inflammation by sympathetic nerves, not the vagus. J Physiol. 2014;592:1677–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Anderson KP. Sympathetic nervous system activity and ventricular tachyarrhythmias: recent advances. Ann Noninvasive Electrocardiol. 2003;8:75–89.

    Article  PubMed  Google Scholar 

  44. Wu CT, Nattel S. Triggering of cardiac arrhythmic events in long QT syndrome: lessons from funny bunnies. J Physiol. 2012;590:1311–2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Roubille C, Richer V, Starnino T, McCourt C, McFarlane A, Fleming P, Siu S, Kraft J, Lynde C, Pope J, Gulliver W, Keeling S, Dutz J, Bessette L, Bissonnette R, Haraoui B. 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. Ann Rheum Dis. 2015;74:480–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Dixon WG, Watson KD, Lunt M, Hyrich KL, British Society for Rheumatology Biologics Register Control Centre Consortium, Silman AJ, Symmons DP, British Society for Rheumatology Biologics Register. Reduction in the incidence of myocardial infarction in patients with rheumatoid arthritis who respond to anti-tumor necrosis factor alpha therapy: results from the British Society for Rheumatology Biologics Register. Arthritis Rheum. 2007;56:2905–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Ikonomidis I, Tzortzis S, Andreadou I, Paraskevaidis I, Katseli C, Katsimbri P, Pavlidis G, Parissis J, Kremastinos D, Anastasiou-Nana M, Lekakis J. Increased benefit of interleukin-1 inhibition on vascular function, myocardial deformation, and twisting in patients with coronary artery disease and coexisting rheumatoid arthritis. Circ Cardiovasc Imaging. 2014;7:619–28.

    Article  PubMed  Google Scholar 

  48. Provan SA, Berg IJ, Hammer HB, Mathiessen A, Kvien TK, Semb AG. The impact of newer biological disease modifying anti-rheumatic drugs on cardiovascular risk factors: a 12-month longitudinal study in rheumatoid arthritis patients treated with rituximab, Abatacept and tociliziumab. PLoS One. 2015;10:e0130709.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Rao VU, Pavlov A, Klearman M, Musselman D, Giles JT, Bathon JM, Sattar N, Lee JS. An evaluation of risk factors for major adverse cardiovascular events during tocilizumab therapy. Arthritis Rheumatol. 2015;67:372–80.

    Article  CAS  PubMed  Google Scholar 

  50. Lazzerini PE, Acampa M, Capecchi PL, Fineschi I, Selvi E, Moscadelli V, Zimbone S, Gentile D, Galeazzi M, Laghi-Pasini F. Antiarrhythmic potential of anti-cytokine therapy in rheumatoid arthritis: tocilizumab reduces QTc interval by controlling systemic inflammation. Arthritis Care Res. 2015;67:332–9.

    Article  CAS  Google Scholar 

  51. Senel S, Cobankara V, Taskoylu O, Guclu A, Evrengul H, Kaya MG. Effect of infliximab treatment on QT intervals in patients with ankylosing spondylitis. J Investig Med. 2011;59:1273–5.

    Article  CAS  PubMed  Google Scholar 

  52. Di Franco M, Paradiso M, Ceccarelli F, Scrivo R, Spinelli FR, Iannuccelli C, Valesini G. Biological drug treatment of rheumatoid arthritis and spondyloarthritis: effects on QT interval and QT dispersion. J Rheumatol. 2012;39:41–5.

    Article  CAS  Google Scholar 

  53. Lazzerini PE, Acampa M, Hammoud M, Maffei S, Capecchi PL, Selvi E, Bisogno S, Guideri F, Galeazzi M, Pasini FL. Arrhythmic risk during acute infusion of infliximab: a prospective, single-blind, placebo-controlled, crossover study in patients with chronic arthritis. J Rheumatol. 2008;35:1958–65.

    CAS  PubMed  Google Scholar 

  54. Syngle A, Verma I, Krishan P, Garg N, Syngle V. Disease-modifying anti-rheumatic drugs improve autonomic neuropathy in arthritis: DIANA study. Clin Rheumatol. 2015;34:1233–41.

    Article  PubMed  Google Scholar 

  55. Syngle A, Verma I, Krishan P. Interleukin-6 blockade improves autonomic dysfunction in rheumatoid arthritis. Acta Reumatol Port. 2015;40:85–8.

    PubMed  Google Scholar 

  56. Meek IL, Vonkeman HE, van de Laar MA. Cardiovascular case fatality in rheumatoid arthritis is decreasing; first prospective analysis of a current low disease activity rheumatoid arthritis cohort and review of the literature. BMC Musculoskelet Disord. 2014;15:142.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  57. Remicade: Infliximab. Product information: summary of product characteristics. European Medicine Agency (EMA). http://www.ema.europa.eu.

  58. Enbrel: Etanercept. Product information: summary of product characteristics. European Medicine Agency (EMA). http://www.ema.europa.eu.

  59. Humira: Adalimumab. Product information: summary of product characteristics. European Medicine Agency (EMA). http://www.ema.europa.eu.

  60. Cimzia: Certolizumab pegol. Product information: summary of product characteristics. European Medicine Agency (EMA). http://www.ema.europa.eu.

  61. Simponi: Golimumab. Product information: summary of product characteristics. European Medicine Agency (EMA). http://www.ema.europa.eu.

  62. MabThera: Rituximab. Product information: summary of product characteristics. European Medicine Agency (EMA). http://www.ema.europa.eu.

  63. RoActemra: Tocilizumab. Product information: summary of product characteristics. European Medicine Agency (EMA). http://www.ema.europa.eu.

  64. Kineret: Anakinra. Product information: summary of product characteristics. European Medicine Agency (EMA). http://www.ema.europa.eu.

  65. Stelara: Ustekinumab. Product information: summary of product characteristics. European Medicine Agency (EMA). http://www.ema.europa.eu.

  66. Orencia: Abatacept. Product information: summary of product characteristics. European Medicine Agency (EMA). http://www.ema.europa.eu.

  67. Clari F, Salani I, Safwan E, Giannacco A. Sudden death in a patient without heart failure after a single infusion of 200 mg infliximab: does TNF-α have protective effects on failing heart, or does infliximab have direct harmful cardiovascular effects? Circulation. 2002;105:E183.

    Article  Google Scholar 

  68. Boyer JF, Jamard B, El Mahou S, Laroche M, Mazieres B, Cantagrel A, Constantin A. New-onset acute heart failure and ventricular tachycardia after therapy with a tumor necrosis factor antagonist. Clin Exp Rheumatol. 2005;23:274–5.

    CAS  PubMed  Google Scholar 

  69. Eder P, Lykowska-Szuber L, Krela-Kazmierczak I, Stawczyk-Eder K, Linke K. Ventricular tachyarrhythmia after adalimumab therapy in a patient with Crohn’s disease. Acta Gastroenterol Belg. 2013;76:74–5.

    CAS  PubMed  Google Scholar 

  70. Ozcan OU, Ozcan DS, Polat CS, Ozyuncu N, Erol C. Ventricular arrhythmia with cessation of infliximab in a patient with ankylosing spondylitis. J Ankara Univ Fac Med. 2015;68:77–9.

    Google Scholar 

  71. Wooten MD, Reddy GV, Johnson RD. Atrial fibrillation occurring in a patient taking etanercept plus methotrexate for rheumatoid arthritis. Del Med J. 2000;72:517–9.

    CAS  PubMed  Google Scholar 

  72. Choi JW, Tae HJ, Oh IH, Lee MK, Shin JH, Kim TH, Jun JB, Uhm WS. A case of atrial fibrillation induced by infliximab in a patient with rheumatoid arthritis. J Rheum Dis. 2011;18:302–5.

    Article  Google Scholar 

  73. Singh M, Diwan MM, Patel KC. A rare case of supraventricular tachycardia induced by infliximab: a case report. Cases J. 2009;2:147.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Sood A, Midha V. Symptomatic sinus bradycardia with infliximab. Indian J Gastroenterol. 2004;23:118–9.

    PubMed  Google Scholar 

  75. Sofos S, Savoye G, Ramirez S, Bauer F, Lerebours E. Transient type III atrioventricular block after infliximab infusion in a fistulizing perianal Crohn’s disease patient. Am J Gastroenterol. 2007;102:217–9.

    PubMed  Google Scholar 

  76. Sote Y, Green S, Maddison P. Complete heart block after infliximab therapy. Rheumatology. 2008;47:227–8.

    Article  CAS  PubMed  Google Scholar 

  77. Anand CP, Al-Juburi A, Bhargava S. Heart block occurring during infliximab infusion: a report of two cases. Am J Gastroenterol. 2003;98:S144.

    Article  Google Scholar 

  78. Gasparyan AY, Ayvazyan L, Cocco G, Kitas GD. Adverse cardiovascular effects of antirheumatic drugs: implications for clinical practice and research. Curr Pharm Des. 2012;18:1543–55.

    Article  CAS  PubMed  Google Scholar 

  79. Foran JM, Rohatiner AZ, Cunningham D, Popescu RA, Solal-Celigny P, Ghielmini M, Coiffier B, Johnson PW, Gisselbrecht C, Reyes F, Radford JA, Bessell EM, Souleau B, Benzohra A, Lister TA. European phase II study of rituximab (chimeric anti-CD20 monoclonal antibody) for patients with newly diagnosed mantle-cell lymphoma and previously treated mantle-cell lymphoma, immunocytoma, and small B-cell lymphocytic lymphoma. J Clin Oncol. 2000;18:317–24.

    Article  CAS  PubMed  Google Scholar 

  80. Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R, Morel P, Van Den Neste E, Salles G, Gaulard P, Reyes F, Lederlin P, Gisselbrecht C. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002;346:235–42.

    Article  CAS  PubMed  Google Scholar 

  81. Moreno M, Sancho JM, Gardella S, Coll R, García O, Gallardo D, Ribera JM. Non-pegylated liposomal doxorubicin in combination with cyclophosphamide, vincristine, prednisone and rituximab for the treatment of non-Hodgkin’s lymphoma: study of 26 patients. Med Clin. 2010;30(134):72–5.

    Article  Google Scholar 

  82. Zaja F, Bacigalupo A, Patriarca F, Stanzani M, Van Lint MT, Filì C, Scimè R, Milone G, Falda M, Vener C, Laszlo D, Alessandrino PE, Narni F, Sica S, Olivieri A, Sperotto A, Bosi A, Bonifazi F, Fanin R, GITMO (Gruppo Italiano Trapianto Midollo Osseo). Treatment of refractory chronic GVHD with rituximab: a GITMO study. Bone Marrow Transpl. 2007;40:273–7.

    Article  CAS  Google Scholar 

  83. Tournamille JF, Rigal-Huguet F, Pathak A, Montastruc JL, Lapeyre-Mestre M. Cardiac effects of cytokines produced after rituximab infusion. Bull Cancer. 2005;92:769–71.

    CAS  PubMed  Google Scholar 

  84. van Sijl AM, van der Weele W, Nurmohamed MT. Myocardial infarction after rituximab treatment for rheumatoid arthritis: is there a link? Curr Pharm Des. 2014;20(4):496–9.

    Article  PubMed  CAS  Google Scholar 

  85. Poterucha JT, Westberg M, Nerheim P, Lovell JP. Rituximab-induced polymorphic ventricular tachycardia. Tex Heart Inst J. 2010;37:218–20.

    PubMed  PubMed Central  Google Scholar 

  86. Arai Y, Tadokoro J, Mitani K. Ventricular tachycardia associated with infusion of rituximab in mantle cell lymphoma. Am J Hematol. 2005;78:317–8.

    Article  PubMed  Google Scholar 

  87. Passalia C, Minetto P, Arboscello E, Balleari E, Bellodi A, Del Corso L, Molinari E, Ponassi I, Oneto C, Sicbaldi V, Ghio R. Cardiovascular adverse events complicating the administration of rituximab: report of two cases. Tumori. 2013;99:288e–92e.

    PubMed  Google Scholar 

  88. Sheikh M, Moza A, Grubb BP. Rituximab induced left bundle branch block. Heart Views. 2015;16:21–2.

    Article  PubMed  PubMed Central  Google Scholar 

  89. Cervera Grau JM, Esquerdo Galiana G, Belso Candela A, Llorca Ferrándiz C, Juárez Marroquí A, Maciá Escalante S. Complete atrioventricular block induced by rituximab in monotherapy in an aged patient with non-Hodgkin’s diffuse large B-cell lymphoma. Clin Transl Oncol. 2008;10:298–9.

    Article  CAS  PubMed  Google Scholar 

  90. Kwon HJ, Coté TR, Cuffe MS, Kramer JM, Braun MM. Case reports of heart failure after therapy with a tumor necrosis factor antagonist. Ann Intern Med. 2003;138:807–11.

    Article  PubMed  Google Scholar 

  91. Chung ES, Packer M, Lo KH, Fasanmade AA, Willerson JT, Anti-TNF Therapy Against Congestive Heart Failure Investigators. Randomized, double-blind, placebo-controlled, pilot trial of infliximab, a chimeric monoclonal antibody to tumor necrosis factor-alpha, in patients with moderate-to-severe heart failure: results of the anti-TNF therapy against congestive heart failure (ATTACH) trial. Circulation. 2003;107:3133–4310.

    Article  CAS  PubMed  Google Scholar 

  92. Hofbauer KH, Schoof E, Kurtz A, Sandner P. Inflammatory cytokines stimulate adrenomedullin expression through nitric oxide-dependent and -independent pathways. Hypertension. 2002;39:161–7.

    Article  CAS  PubMed  Google Scholar 

  93. Irace C, Mancuso G, Fiaschi E, Madia A, Sesti G, Gnasso A. Effect of anti TNFalpha therapy on arterial diameter and wall shear stress and HDL cholesterol. Atherosclerosis. 2004;177:113–8.

    Article  CAS  PubMed  Google Scholar 

  94. Abedin M, Scheurich D, Reimold SC, Reimold AM. Acute coronary syndrome after infliximab infusion. Cardiol Rev. 2006;14:50–2.

    Article  PubMed  Google Scholar 

  95. Panteris V, Perdiou A, Tsirimpis V, Karamanolis DG. Acute coronary syndrome after infliximab therapy in a patient with Crohn’s disease. World J Gastroenterol. 2006;12:6235–8.

    Article  PubMed  PubMed Central  Google Scholar 

  96. Kumar A, Ghose T, Mendiratta N, Prajapati PK, Abrol A. Acute coronary syndrome caused by infliximab in a patient with ankylosing spondylitis. Int J Rheum Dis. 2013;16:235–6.

    Article  PubMed  Google Scholar 

  97. Sarzi-Puttini P, Atzeni F, Shoenfeld Y, Ferraccioli G. TNF-alpha, rheumatoid arthritis, and heart failure: a rheumatological dilemma. Autoimmun Rev. 2005;4:153–61.

    Article  CAS  PubMed  Google Scholar 

  98. Mitoma H, Horiuchi T, Tsukamoto H, Tamimoto Y, Kimoto Y, Uchino A, To K, Harashima S, Hatta N, Harada M. Mechanisms for cytotoxic effects of anti-tumor necrosis factor agents on transmembrane tumor necrosis factor alpha-expressing cells: comparison among infliximab, etanercept, and adalimumab. Arthritis Rheum. 2008;58:1248–57.

    Article  CAS  PubMed  Google Scholar 

  99. Kaymakcalan Z, Sakorafas P, Bose S, Scesney S, Xiong L, Hanzatian DK, Salfeld J, Sasso EH. Comparisons of affinities, avidities, and complement activation of adalimumab, infliximab, and etanercept in binding to soluble and membrane tumor necrosis factor. Clin Immunol. 2009;131:308–1316.

    Article  CAS  PubMed  Google Scholar 

  100. Torre-Amione G, Bozkurt B, Deswal A, Mann DL. An overview of tumor necrosis factor alpha and the failing human heart. Curr Opin Cardiol. 1999;14:206–10.

    Article  CAS  PubMed  Google Scholar 

  101. Rossi MA, Celes MR, Prado CM, Saggioro FP. Myocardial structural changes in long-term human severe sepsis/septic shock may be responsible for cardiac dysfunction. Shock. 2007;27:10–8.

    Article  CAS  PubMed  Google Scholar 

  102. Zhang XJ, Yue J, Zhao TB. Expression change of TNF-α in myocardium and hepatic tissue of rats with compound stress of hyperthermia and lipopolysaccharide. Asian Pac J Trop Med. 2013;6:300–4.

    Article  CAS  PubMed  Google Scholar 

  103. Bonnemeier H, Wiegand UKH, Brandes A, Kluge N, Katus HA, Richardt G, Potratz J. Circadian profile of cardiac autonomic nervous modulation in healthy subjects: differing effects of aging and gender on heart rate variability. J Cardiovasc Electrophysiol. 2003;14:8791–9.

    Article  Google Scholar 

  104. Tvede N, Nielsen LP, Andersen V. Bradycardia after high-dose intravenous methylprednisolone therapy. Scand J Rheumatol. 1986;15:302–4.

    Article  CAS  PubMed  Google Scholar 

  105. Pudil R, Hrncir Z. Severe bradycardia after a methylprednisolone “minipulse” treatment. Arch Intern Med. 2001;161:1778–9.

    Article  CAS  PubMed  Google Scholar 

  106. Akikusa JD, Feldman BM, Gross GJ, Silverman ED, Schneider R. Sinus bradycardia after intravenous pulse methylprednisolone. Pediatrics. 2007;119:e778–82.

    Article  PubMed  Google Scholar 

  107. Winkler U, Jensen M, Manzke O, Schulz H, Diehl V, Engert A. Cytokine-release syndrome in patients with B-cell chronic lymphocytic leukemia and high lymphocyte counts after treatment with an anti-CD20 monoclonal antibody (rituximab, IDEC-C2B8). Blood. 1999;94:2217–24.

    CAS  PubMed  Google Scholar 

  108. Agarwal A, Vieira CA, Book BK, Sidner RA, Fineberg NS, Pescovitz MD. Rituximab, anti-CD20, induces in vivo cytokine release but does not impair ex vivo T-cell responses. Am J Transplant. 2004;4:1357–60.

    Article  CAS  PubMed  Google Scholar 

  109. Pescovitz MD. Rituximab, an anti-cd20 monoclonal antibody: history and mechanism of action. Am J Transpl. 2006;6:859–66.

    Article  CAS  Google Scholar 

  110. Kumar A, Thota V, Dee L, Olson J, Uretz E, Parrillo JE. Tumor necrosis factor alpha and interleukin 1beta are responsible for in vitro myocardial cell depression induced by human septic shock serum. J Exp Med. 1996;183:949–58.

    Article  CAS  PubMed  Google Scholar 

  111. Hofmann U, Heuer S, Meder K, Boehler J, Lange V, Quaschning T, Ertl G, Bonz A. The proinflammatory cytokines TNF-alpha and IL-1 beta impair economy of contraction in human myocardium. Cytokine. 2007;39:157–62.

    Article  CAS  PubMed  Google Scholar 

  112. Aukrust P, Sandberg WJ, Otterdal K, Vinge LE, Gullestad L, Yndestad A, Halvorsen B, Ueland T. Tumor necrosis factor superfamily molecules in acute coronary syndromes. Ann Med. 2011;43:90–103.

    Article  CAS  PubMed  Google Scholar 

  113. Armitage JD, Montero C, Benner A, Armitage JO, Bociek G. Acute coronary syndromes complicating the first infusion of rituximab. Clin Lymphoma Myeloma. 2008;8:253–5.

    Article  PubMed  Google Scholar 

  114. Roy A, Khanna N, Senguttuvan NB. Rituximab-vincristine chemotherapy-induced acute anterior wall myocardial infarction with cardiogenic shock. Tex Heart Inst J. 2014;41:80–2.

    Article  PubMed  PubMed Central  Google Scholar 

  115. Gogia A, Khurana S, Paramanik R. Acute myocardial infarction after first dose of rituximab infusion. Turk J Haematol. 2014;31:95–6.

    Article  PubMed  PubMed Central  Google Scholar 

  116. Arunprasath P, Gobu P, Dubashi B, Satheesh S, Balachander J. Rituximab induced myocardial infarction: a fatal drug reaction. J Cancer Res Ther. 2011;7:346–8.

    Article  PubMed  Google Scholar 

  117. Nikolaidis LA. When cancer and heart failure cross paths: a case report of severe cardiorenal compromise associated with the anti-CD20 monoclonal antibody rituximab in a patient with dilated cardiomyopathy. Congest Heart Fail. 2001;7:223–7.

    Article  CAS  PubMed  Google Scholar 

  118. Renard D, Cornillet L, Castelnovo G. Myocardial infarction after rituximab infusion. Neuromuscul Disord. 2013;23:599–601.

    Article  PubMed  Google Scholar 

  119. Millward PM, Bandarenko N, Chang PP, Stagg KF, Afenyi-Annan A, Hay SN, Brecher ME. Cardiogenic shock complicates successful treatment of refractory thrombotic thrombocytopenia purpura with rituximab. Transfusion. 2005;45:1481–6.

    Article  CAS  PubMed  Google Scholar 

  120. Maloney DG, Liles TM, Czerwinski DK, Waldichuk C, Rosenberg J, Grillo-Lopez A, Levy R. Phase I clinical trial using escalating single-dose infusion of chimeric anti-CD20 monoclonal antibody (IDEC-C2B8) in patients with recurrent B-cell lymphoma. Blood. 1994;84:2457–66.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Policlinico “Le Scotte”, Viale Bracci, Siena, Italy

    Pietro Enea Lazzerini, Pier Leopoldo Capecchi, Mauro Galeazzi & Franco Laghi-Pasini

Authors
  1. Pietro Enea Lazzerini
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Pier Leopoldo Capecchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mauro Galeazzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Franco Laghi-Pasini
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Pietro Enea Lazzerini.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lazzerini, P.E., Capecchi, P.L., Galeazzi, M. et al. Biologic drugs and arrhythmic risk in chronic inflammatory arthritis: the good and the bad. Immunol Res 65, 262–275 (2017). https://doi.org/10.1007/s12026-016-8833-7

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12026-016-8833-7

Keywords

Search

Navigation