Case Reports
Anakinra for Myocarditis in Juvenile Idiopathic Arthritis
Rajesh Movva, MD, MRCP Suzanne B. Brown, MD D. Lynn Morris, MD Vincent M. Figueredo, MD, FACC
A 20-year-old pregnant woman with a history of juvenile idiopathic arthritis presented with flu-like symptoms, systemic inflammation with myocarditis, and severe cardiomyopathy. Six weeks earlier, her chronic-arthritis therapy had been changed from anakinra, an interleukin-1β receptor antagonist, to etanercept. When she resumed taking anakinra, her condition improved dramatically, including a complete recovery of ventricular function. Myocarditis is a well-recognized complication of systemic vasculitides. This unusual case emphasizes the important pathophysiologic role of interleukin receptors in the successful treatment of myocarditis. We suggest that clinical cardiologists be aware of the therapeutic usefulness of biological agents such as anakinra in patients with rheumatic conditions. (Tex Heart Inst J 2013;40(5):623-5)
C Key words: Anti-inflam matory agents/therapeutic use; antirheumatic agents/ therapeutic use; arthritis, juvenile rheumatoid/ complications/drug therapy; disease susceptibility; heart/ drug effects; interferon-beta/ therapeutic use; interleukin 1 receptor antagonist protein; myocarditis/diagnosis; treatment outcome; ventricular dysfunction, left / drug effects From: Division of Cardiology (Drs. Brown, Figueredo, Morris, and Movva), Einstein Medical Center, Philadelphia, Pennsylvania 19141; and Department of Medicine (Drs. Figueredo and Morris), Jefferson Medical College, Philadelphia, Pennsylvania 19107 Address for reprints: Vincent M. Figueredo, MD, Einstein Institute for Heart & Vascular Health, Einstein Medical Center, 5501 Old York Rd., Philadelphia, PA 19141 E-mail: [email protected] © 2013 by the Texas Heart ® Institute, Houston
Texas Heart Institute Journal
ardiac involvement in chronic rheumatic conditions is well recognized and is possibly associated with higher cardiovascular morbidity and mortality rates. The cardiac manifestations include vasculitis, accelerated atherosclerosis, congestive heart failure, valvular abnormalities, pulmonary hypertension, conduction system abnormalities, pericarditis, and myocarditis. Immunologic mediators such as interleukin-1, tumor necrosis factor (TNF), and other cytokines play a key role in the pathophysiologic course of chronic rheumatic conditions and their cardiac manifestations. It is crucial to recognize cardiac abnormalities and to initiate anti-inflammatory therapies promptly. We describe the case of a young woman with a history of juvenile idiopathic arthritis who presented with myocarditis, and we discuss the outcome of her therapy with an interleukin-1β receptor antagonist.
Case Report A 20-year-old white woman, 24 weeks’ pregnant, was admitted with a oneweek history of fever, sore throat, vomiting, diarrhea, and generalized body aches. At the age of 8 years, she had been diagnosed with juvenile idiopathic arthritis (JIA). This condition had been well controlled with anakinra, an interleukin-1β receptor antagonist. Six weeks before the current admission, the anakinra had been replaced with etanercept because of a change in the patient’s insurance coverage. On examination, she was tachycardic, febrile, and dyspneic, and she developed hypoxia and hypotension. Pulmonary embolism was excluded, and a chest radiograph showed mild pulmonary interstitial edema. An electrocardiogram showed anterolateral ST-segment depressions and T-wave inversions. The patient’s cardiac troponin I levels were 0.41 and 0.67 ng/mL 6 hours apart, and her brain natriuretic peptide level was 280 pg/mL. Her hemoglobin level was 8.7 g/dL. Viral titers were negative. The patient’s inflammatory markers were elevated. An echocardiogram showed moderate right ventricular dysfunction and a left ventricular ejection fraction (LVEF) of 0.20 with severe diffuse hypokinesis. Right-sided heart catheterization yielded a mean pulmonary capillary wedge pressure of 18 mmHg, a pulmonary artery pressure of 37/28 mmHg, a cardiac output of 10.9 L/min, and a cardiac index of 5.11 L/min/m2. The patient was started on inotropic agents and high-dose pulse steroids, and the etanercept therapy was discontinued. However, her clinical condition did not improve: dyspnea (despite diuresis), intermittent fever, and persistent tachycardia (130–140 beats/min) and hypotension (systolic blood pressure, 80–90 mmHg) necessitated inotropic therapy. Six days after admission, she was restarted on anakinra, and her symptoms improved dramatically within 24 hours. This improvement coincided with Anakinra for Myocarditis in Juvenile Arthritis
623
a major increase in LVEF to 0.55 and a return to normal right ventricular systolic function, as revealed on an echocardiogram obtained 3 days after the anakinra was resumed. She was discharged from the hospital the next day, in stable condition.
Discussion The differential diagnosis in this case included JIA-induced myocarditis or cardiomyopathy, viral myocarditis, etanercept-induced heart failure, non-ST-segment-elevation myocardial infarction, peripartum cardiomyopathy, and stress-induced cardiomyopathy. The evolution of systemic symptoms over only a few days—combined with mildly elevated cardiac biomarkers, electrocardiographic changes, a lack of segmental wall-motion abnormalities, and elevated inflammatory markers— suggested a diagnosis of JIA flare-up, with myocarditis leading to severe cardiomyopathy. The cardiac output was elevated disproportionately to the grossly decreased left ventricular (LV) systolic function; however, this could be explained by the patient’s anemia and pregnancy. The rapid improvement in symptoms and LVEF soon after resumption of anakinra therapy also supported a diagnosis of an acute inflammatory process, rather than one of chronic decompensated cardiomyopathy. Myocarditis as part of the systemic inflammatory process can be found in up to 5% of JIA patients, with recurrence in up to 60%. Of note, most women report either no change or an overall amelioration in JIA activity during pregnancy. Elevations in white blood cell count, sedimentation rate, C-reactive protein, and ferritin, although nonspecific, might provide diagnostic clues. Viral titers should be measured. Although we did not perform cardiac magnetic resonance in our patient, this method can reveal a hyperenhancement-sparing subendocardium characteristic of myocarditis. In addition, cardiac catheterization and a myocardial biopsy can be considered, if they are clinically indicated. The conventional therapy for acute myocarditis is to support the LV function. Most patients improve when placed on a standard therapeutic regimen that includes an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, a β-blocker, and a diuretic, if needed. In patients whose condition deteriorates despite optimal medical management, mechanical circulatory support such as ventricular assist devices or extracorporeal membrane oxygenation can be considered as a bridge to transplantation or recovery. In patients with viral persistence in chronic, stable dilated cardiomyopathy, interferon-β has led to viral clearance and substantial improvement in LV function.1 In patients with biopsy-proven, virus-negative inflammatory cardiomyopathy, immunosuppressive therapy appears to be effective and safe in combination with supportive treatment for cardiac failure.2 Intravenous gamma globulin has 624
Anakinra for Myocarditis in Juvenile Arthritis
been associated with improved recovery of LV function and a trend toward better survival rates in children with acute myocarditis.3 In a small retrospective study, this therapy improved LVEFs in women who had peripartum cardiomyopathy.4 Interleukin-1 is thought to play a key role in the pathogenesis of JIA. Conventional therapies for JIA include nonsteroidal anti-inflammatory agents and corticosteroids. Treatment with TNF-a antagonists has produced variable results. In one study, etanercept significantly improved LVEF and LV remodeling.5 Conversely, in 2 larger randomized trials, etanercept had no effect on mortality rates or on hospitalization for heart failure,6 and therapy with infliximab resulted in an increased risk of those endpoints.7 Of note, TNF-a antagonists are not recommended in patients with New York Heart Association functional class III–IV heart failure or class I–II heart failure with depressed LV function.8 Anakinra has been used successfully as a first-line therapy for JIA; however, its cardiac effects vary. On one hand, dilated cardiomyopathy and sudden cardiac death have been reported after therapy with anakinra,9,10 but so have major improvements in cardiac tamponade11 and myocarditis.12 Anakinra has improved LV function after 30 days of therapy, as evaluated by improvements in coronary flow reserve and mitral annular velocities.13 In addition, vascular function (evaluated by flow-mediated, endothelial-dependent dilation) and aortic distensibility have improved.5 Anakinra has significantly ameliorated the ventricular remodeling process by inhibiting cardiac apoptosis in experimental studies of acute myocardial infarction14,15 and has provided protection against ischemia-reperfusion injury.16 After ST-segment-elevation myocardial infarction, the subcutaneous administration of anakinra significantly improved LV end-systolic and end-diastolic volume indices, as well as C-reactive protein levels.17 Currently, there is insufficient evidence regarding the use of anakinra during pregnancy.18,19 Systemic vasculitides are associated with a wide range of cardiac manifestations. Rheumatologists are now using novel biological therapies to treat these conditions. We consider it important for clinical cardiologists to be aware of the potential cardiac complications of these diseases and the increasing number of therapies available to treat them.
References 1. Kuhl U, Pauschinger M, Schwimmbeck PL, Seeberg B, Lober C, Noutsias M, et al. Interferon-beta treatment eliminates cardiotropic viruses and improves left ventricular function in patients with myocardial persistence of viral genomes and left ventricular dysfunction. Circulation 2003;107(22):2793-8. 2. Schultheiss HP, Kuhl U, Cooper LT. The management of myocarditis. Eur Heart J 2011;32(21):2616-25. 3. Drucker NA, Colan SD, Lewis AB, Beiser AS, Wessel DL, Takahashi M, et al. Gamma-globulin treatment of acute myo-
Volume 40, Number 5, 2013
4.
5.
6.
7.
8. 9.
10.
11.
carditis in the pediatric population. Circulation 1994;89(1): 252-7. Bozkurt B, Villaneuva FS, Holubkov R, Tokarczyk T, Alvarez RJ Jr, MacGowan GA, et al. Intravenous immune globulin in the therapy of peripartum cardiomyopathy. J Am Coll Cardiol 1999;34(1):177-80. Bozkurt B, Torre-Amione G, Warren MS, Whitmore J, Soran OZ, Feldman AM, Mann DL. Results of targeted anti-tumor necrosis factor therapy with etanercept (ENBREL) in patients with advanced heart failure. Circulation 2001;103(8):1044-7. Mann DL, McMurray JJ, Packer M, Swedberg K, Borer JS, Colucci WS, et al. Targeted anticytokine therapy in patients with chronic heart failure: results of the Randomized Etanercept Worldwide Evaluation (RENEWAL). Circulation 2004;109(13):1594-602. 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-tosevere heart failure: results of the anti-TNF Therapy Against Congestive Heart Failure (ATTACH) trial. Circulation 2003;107(25):3133-40. Lin J, Ziring D, Desai S, Kim S, Wong M, Korin Y, et al. TNF alpha blockade in human diseases: an overview of efficacy and safety. Clin Immunol 2008;126(1):13-30. Zeft AS, Menon SC, Miller D. Fatal myocarditis in a child with systemic onset juvenile idiopathic arthritis during treatment with an interleukin 1 receptor antagonist. Pediatr Rheumatol Online J 2012;10:8. Ruiz PJ, Masliah E, Doherty TA, Quach A, Firestein GS. Cardiac death in a patient with adult-onset Still’s disease treated with the interleukin 1 receptor inhibitor anakinra. Ann Rheum Dis 2007;66(3):422-3. Merlin E, Berthomieu L, Dauphin C, Stephan JL. Cardiac tamponade in a child with systemic-onset juvenile idiopathic arthritis: dramatic improvement after interleukin-1 blockade by anakinra. Pediatr Cardiol 2011;32(6):862-3.
Texas Heart Institute Journal
12. Raffeiner B, Botsios C, Dinarello C, Ometto F, Punzi L, Ramonda R. Adult-onset Still’s disease with myocarditis successfully treated with the interleukin-1 receptor antagonist anakinra. Joint Bone Spine 2011;78(1):100-1. 13. Ikonomidis I, Lekakis JP, Nikolaou M, Paraskevaidis I, Andreadou I, Kaplanoglou T, et al. Inhibition of interleukin-1 by anakinra improves vascular and left ventricular function in patients with rheumatoid arthritis. Circulation 2008;117(20):2662-9. 14. Salloum FN, Chau V, Varma A, Hoke NN, Toldo S, BiondiZoccai GG, et al. Anakinra in experimental acute myocardial infarction--does dosage or duration of treatment matter? Cardiovasc Drugs Ther 2009;23(2):129-35. 15. Abbate A, Salloum FN, Vecile E, Das A, Hoke NN, Straino S, et al. Anakinra, a recombinant human interleukin-1 receptor antagonist, inhibits apoptosis in experimental acute myocardial infarction. Circulation 2008;117(20):2670-83. 16. Suzuki K, Murtuza B, Smolenski RT, Sammut IA, Suzuki N, Kaneda Y, Yacoub MH. Overexpression of interleukin-1 receptor antagonist provides cardioprotection against ischemiareperfusion injury associated with reduction in apoptosis. Circulation 2001;104(12 Suppl 1):I308-I3. 17. Abbate A, Kontos MC, Grizzard JD, Biondi-Zoccai GG, Van Tassell BW, Robati R, et al. Interleukin-1 blockade with anakinra to prevent adverse cardiac remodeling after acute myocardial infarction (Virginia Commonwealth University Anakinra Remodeling Trial [VCU-ART] Pilot study). Am J Cardiol 2010;105(10):1371-7.e1. 18. Berger CT, Recher M, Steiner U, Hauser TM. A patient’s wish: anakinra in pregnancy [published erratum appears in Ann Rheum Dis 2010;69(1):28]. Ann Rheum Dis 2009;68 (11):1794-5. 19. Fischer-Betz R, Specker C, Schneider M. Successful outcome of two pregnancies in patients with adult-onset Still’s disease treated with IL-1 receptor antagonist (anakinra). Clin Exp Rheumatol 2011;29(6):1021-3.
Anakinra for Myocarditis in Juvenile Arthritis
625
Anakinra for Myocarditis in Juvenile Idiopathic Arthritis
Rajesh Movva, MD, MRCP Suzanne B. Brown, MD D. Lynn Morris, MD Vincent M. Figueredo, MD, FACC
A 20-year-old pregnant woman with a history of juvenile idiopathic arthritis presented with flu-like symptoms, systemic inflammation with myocarditis, and severe cardiomyopathy. Six weeks earlier, her chronic-arthritis therapy had been changed from anakinra, an interleukin-1β receptor antagonist, to etanercept. When she resumed taking anakinra, her condition improved dramatically, including a complete recovery of ventricular function. Myocarditis is a well-recognized complication of systemic vasculitides. This unusual case emphasizes the important pathophysiologic role of interleukin receptors in the successful treatment of myocarditis. We suggest that clinical cardiologists be aware of the therapeutic usefulness of biological agents such as anakinra in patients with rheumatic conditions. (Tex Heart Inst J 2013;40(5):623-5)
C Key words: Anti-inflam matory agents/therapeutic use; antirheumatic agents/ therapeutic use; arthritis, juvenile rheumatoid/ complications/drug therapy; disease susceptibility; heart/ drug effects; interferon-beta/ therapeutic use; interleukin 1 receptor antagonist protein; myocarditis/diagnosis; treatment outcome; ventricular dysfunction, left / drug effects From: Division of Cardiology (Drs. Brown, Figueredo, Morris, and Movva), Einstein Medical Center, Philadelphia, Pennsylvania 19141; and Department of Medicine (Drs. Figueredo and Morris), Jefferson Medical College, Philadelphia, Pennsylvania 19107 Address for reprints: Vincent M. Figueredo, MD, Einstein Institute for Heart & Vascular Health, Einstein Medical Center, 5501 Old York Rd., Philadelphia, PA 19141 E-mail: [email protected] © 2013 by the Texas Heart ® Institute, Houston
Texas Heart Institute Journal
ardiac involvement in chronic rheumatic conditions is well recognized and is possibly associated with higher cardiovascular morbidity and mortality rates. The cardiac manifestations include vasculitis, accelerated atherosclerosis, congestive heart failure, valvular abnormalities, pulmonary hypertension, conduction system abnormalities, pericarditis, and myocarditis. Immunologic mediators such as interleukin-1, tumor necrosis factor (TNF), and other cytokines play a key role in the pathophysiologic course of chronic rheumatic conditions and their cardiac manifestations. It is crucial to recognize cardiac abnormalities and to initiate anti-inflammatory therapies promptly. We describe the case of a young woman with a history of juvenile idiopathic arthritis who presented with myocarditis, and we discuss the outcome of her therapy with an interleukin-1β receptor antagonist.
Case Report A 20-year-old white woman, 24 weeks’ pregnant, was admitted with a oneweek history of fever, sore throat, vomiting, diarrhea, and generalized body aches. At the age of 8 years, she had been diagnosed with juvenile idiopathic arthritis (JIA). This condition had been well controlled with anakinra, an interleukin-1β receptor antagonist. Six weeks before the current admission, the anakinra had been replaced with etanercept because of a change in the patient’s insurance coverage. On examination, she was tachycardic, febrile, and dyspneic, and she developed hypoxia and hypotension. Pulmonary embolism was excluded, and a chest radiograph showed mild pulmonary interstitial edema. An electrocardiogram showed anterolateral ST-segment depressions and T-wave inversions. The patient’s cardiac troponin I levels were 0.41 and 0.67 ng/mL 6 hours apart, and her brain natriuretic peptide level was 280 pg/mL. Her hemoglobin level was 8.7 g/dL. Viral titers were negative. The patient’s inflammatory markers were elevated. An echocardiogram showed moderate right ventricular dysfunction and a left ventricular ejection fraction (LVEF) of 0.20 with severe diffuse hypokinesis. Right-sided heart catheterization yielded a mean pulmonary capillary wedge pressure of 18 mmHg, a pulmonary artery pressure of 37/28 mmHg, a cardiac output of 10.9 L/min, and a cardiac index of 5.11 L/min/m2. The patient was started on inotropic agents and high-dose pulse steroids, and the etanercept therapy was discontinued. However, her clinical condition did not improve: dyspnea (despite diuresis), intermittent fever, and persistent tachycardia (130–140 beats/min) and hypotension (systolic blood pressure, 80–90 mmHg) necessitated inotropic therapy. Six days after admission, she was restarted on anakinra, and her symptoms improved dramatically within 24 hours. This improvement coincided with Anakinra for Myocarditis in Juvenile Arthritis
623
a major increase in LVEF to 0.55 and a return to normal right ventricular systolic function, as revealed on an echocardiogram obtained 3 days after the anakinra was resumed. She was discharged from the hospital the next day, in stable condition.
Discussion The differential diagnosis in this case included JIA-induced myocarditis or cardiomyopathy, viral myocarditis, etanercept-induced heart failure, non-ST-segment-elevation myocardial infarction, peripartum cardiomyopathy, and stress-induced cardiomyopathy. The evolution of systemic symptoms over only a few days—combined with mildly elevated cardiac biomarkers, electrocardiographic changes, a lack of segmental wall-motion abnormalities, and elevated inflammatory markers— suggested a diagnosis of JIA flare-up, with myocarditis leading to severe cardiomyopathy. The cardiac output was elevated disproportionately to the grossly decreased left ventricular (LV) systolic function; however, this could be explained by the patient’s anemia and pregnancy. The rapid improvement in symptoms and LVEF soon after resumption of anakinra therapy also supported a diagnosis of an acute inflammatory process, rather than one of chronic decompensated cardiomyopathy. Myocarditis as part of the systemic inflammatory process can be found in up to 5% of JIA patients, with recurrence in up to 60%. Of note, most women report either no change or an overall amelioration in JIA activity during pregnancy. Elevations in white blood cell count, sedimentation rate, C-reactive protein, and ferritin, although nonspecific, might provide diagnostic clues. Viral titers should be measured. Although we did not perform cardiac magnetic resonance in our patient, this method can reveal a hyperenhancement-sparing subendocardium characteristic of myocarditis. In addition, cardiac catheterization and a myocardial biopsy can be considered, if they are clinically indicated. The conventional therapy for acute myocarditis is to support the LV function. Most patients improve when placed on a standard therapeutic regimen that includes an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, a β-blocker, and a diuretic, if needed. In patients whose condition deteriorates despite optimal medical management, mechanical circulatory support such as ventricular assist devices or extracorporeal membrane oxygenation can be considered as a bridge to transplantation or recovery. In patients with viral persistence in chronic, stable dilated cardiomyopathy, interferon-β has led to viral clearance and substantial improvement in LV function.1 In patients with biopsy-proven, virus-negative inflammatory cardiomyopathy, immunosuppressive therapy appears to be effective and safe in combination with supportive treatment for cardiac failure.2 Intravenous gamma globulin has 624
Anakinra for Myocarditis in Juvenile Arthritis
been associated with improved recovery of LV function and a trend toward better survival rates in children with acute myocarditis.3 In a small retrospective study, this therapy improved LVEFs in women who had peripartum cardiomyopathy.4 Interleukin-1 is thought to play a key role in the pathogenesis of JIA. Conventional therapies for JIA include nonsteroidal anti-inflammatory agents and corticosteroids. Treatment with TNF-a antagonists has produced variable results. In one study, etanercept significantly improved LVEF and LV remodeling.5 Conversely, in 2 larger randomized trials, etanercept had no effect on mortality rates or on hospitalization for heart failure,6 and therapy with infliximab resulted in an increased risk of those endpoints.7 Of note, TNF-a antagonists are not recommended in patients with New York Heart Association functional class III–IV heart failure or class I–II heart failure with depressed LV function.8 Anakinra has been used successfully as a first-line therapy for JIA; however, its cardiac effects vary. On one hand, dilated cardiomyopathy and sudden cardiac death have been reported after therapy with anakinra,9,10 but so have major improvements in cardiac tamponade11 and myocarditis.12 Anakinra has improved LV function after 30 days of therapy, as evaluated by improvements in coronary flow reserve and mitral annular velocities.13 In addition, vascular function (evaluated by flow-mediated, endothelial-dependent dilation) and aortic distensibility have improved.5 Anakinra has significantly ameliorated the ventricular remodeling process by inhibiting cardiac apoptosis in experimental studies of acute myocardial infarction14,15 and has provided protection against ischemia-reperfusion injury.16 After ST-segment-elevation myocardial infarction, the subcutaneous administration of anakinra significantly improved LV end-systolic and end-diastolic volume indices, as well as C-reactive protein levels.17 Currently, there is insufficient evidence regarding the use of anakinra during pregnancy.18,19 Systemic vasculitides are associated with a wide range of cardiac manifestations. Rheumatologists are now using novel biological therapies to treat these conditions. We consider it important for clinical cardiologists to be aware of the potential cardiac complications of these diseases and the increasing number of therapies available to treat them.
References 1. Kuhl U, Pauschinger M, Schwimmbeck PL, Seeberg B, Lober C, Noutsias M, et al. Interferon-beta treatment eliminates cardiotropic viruses and improves left ventricular function in patients with myocardial persistence of viral genomes and left ventricular dysfunction. Circulation 2003;107(22):2793-8. 2. Schultheiss HP, Kuhl U, Cooper LT. The management of myocarditis. Eur Heart J 2011;32(21):2616-25. 3. Drucker NA, Colan SD, Lewis AB, Beiser AS, Wessel DL, Takahashi M, et al. Gamma-globulin treatment of acute myo-
Volume 40, Number 5, 2013
4.
5.
6.
7.
8. 9.
10.
11.
carditis in the pediatric population. Circulation 1994;89(1): 252-7. Bozkurt B, Villaneuva FS, Holubkov R, Tokarczyk T, Alvarez RJ Jr, MacGowan GA, et al. Intravenous immune globulin in the therapy of peripartum cardiomyopathy. J Am Coll Cardiol 1999;34(1):177-80. Bozkurt B, Torre-Amione G, Warren MS, Whitmore J, Soran OZ, Feldman AM, Mann DL. Results of targeted anti-tumor necrosis factor therapy with etanercept (ENBREL) in patients with advanced heart failure. Circulation 2001;103(8):1044-7. Mann DL, McMurray JJ, Packer M, Swedberg K, Borer JS, Colucci WS, et al. Targeted anticytokine therapy in patients with chronic heart failure: results of the Randomized Etanercept Worldwide Evaluation (RENEWAL). Circulation 2004;109(13):1594-602. 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-tosevere heart failure: results of the anti-TNF Therapy Against Congestive Heart Failure (ATTACH) trial. Circulation 2003;107(25):3133-40. Lin J, Ziring D, Desai S, Kim S, Wong M, Korin Y, et al. TNF alpha blockade in human diseases: an overview of efficacy and safety. Clin Immunol 2008;126(1):13-30. Zeft AS, Menon SC, Miller D. Fatal myocarditis in a child with systemic onset juvenile idiopathic arthritis during treatment with an interleukin 1 receptor antagonist. Pediatr Rheumatol Online J 2012;10:8. Ruiz PJ, Masliah E, Doherty TA, Quach A, Firestein GS. Cardiac death in a patient with adult-onset Still’s disease treated with the interleukin 1 receptor inhibitor anakinra. Ann Rheum Dis 2007;66(3):422-3. Merlin E, Berthomieu L, Dauphin C, Stephan JL. Cardiac tamponade in a child with systemic-onset juvenile idiopathic arthritis: dramatic improvement after interleukin-1 blockade by anakinra. Pediatr Cardiol 2011;32(6):862-3.
Texas Heart Institute Journal
12. Raffeiner B, Botsios C, Dinarello C, Ometto F, Punzi L, Ramonda R. Adult-onset Still’s disease with myocarditis successfully treated with the interleukin-1 receptor antagonist anakinra. Joint Bone Spine 2011;78(1):100-1. 13. Ikonomidis I, Lekakis JP, Nikolaou M, Paraskevaidis I, Andreadou I, Kaplanoglou T, et al. Inhibition of interleukin-1 by anakinra improves vascular and left ventricular function in patients with rheumatoid arthritis. Circulation 2008;117(20):2662-9. 14. Salloum FN, Chau V, Varma A, Hoke NN, Toldo S, BiondiZoccai GG, et al. Anakinra in experimental acute myocardial infarction--does dosage or duration of treatment matter? Cardiovasc Drugs Ther 2009;23(2):129-35. 15. Abbate A, Salloum FN, Vecile E, Das A, Hoke NN, Straino S, et al. Anakinra, a recombinant human interleukin-1 receptor antagonist, inhibits apoptosis in experimental acute myocardial infarction. Circulation 2008;117(20):2670-83. 16. Suzuki K, Murtuza B, Smolenski RT, Sammut IA, Suzuki N, Kaneda Y, Yacoub MH. Overexpression of interleukin-1 receptor antagonist provides cardioprotection against ischemiareperfusion injury associated with reduction in apoptosis. Circulation 2001;104(12 Suppl 1):I308-I3. 17. Abbate A, Kontos MC, Grizzard JD, Biondi-Zoccai GG, Van Tassell BW, Robati R, et al. Interleukin-1 blockade with anakinra to prevent adverse cardiac remodeling after acute myocardial infarction (Virginia Commonwealth University Anakinra Remodeling Trial [VCU-ART] Pilot study). Am J Cardiol 2010;105(10):1371-7.e1. 18. Berger CT, Recher M, Steiner U, Hauser TM. A patient’s wish: anakinra in pregnancy [published erratum appears in Ann Rheum Dis 2010;69(1):28]. Ann Rheum Dis 2009;68 (11):1794-5. 19. Fischer-Betz R, Specker C, Schneider M. Successful outcome of two pregnancies in patients with adult-onset Still’s disease treated with IL-1 receptor antagonist (anakinra). Clin Exp Rheumatol 2011;29(6):1021-3.
Anakinra for Myocarditis in Juvenile Arthritis
625
