Blocking interleukin-1 as a novel therapeutic strategy for secondary prevention of cardiovascular events

BioDrugs

Volumn 26, Issue 4, 2012, Pages 217-233

  Abbate, Antonio ^a   Van Tassell, Benjamin W ^a   Biondi Zoccai, Giuseppe G L ^b  

^a VIRGINIA COMMONWEALTH UNIVERSITY   (United States)

^b SAPIENZA UNIVERSITY OF ROME   (Italy)

Author keywords

Atherosclerosis; Cardiovascular therapies; Inflammation; Interleukin 1

Indexed keywords

C REACTIVE PROTEIN; CANAKINUMAB; ETANERCEPT; GAMMA INTERFERON; GEVOKIZUMAB; HEMOGLOBIN A1C; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INFLIXIMAB; INTERLEUKIN 1; INTERLEUKIN 1ALPHA; INTERLEUKIN 1BETA; INTERLEUKIN 1BETA CONVERTING ENZYME; INTERLEUKIN 6; MELOXICAM; MONOCYTE CHEMOTACTIC PROTEIN 1; PLACEBO; RECOMBINANT INTERLEUKIN 1 RECEPTOR BLOCKING AGENT; RILONACEPT; ROFECOXIB; ROSUVASTATIN; SERUM AMYLOID A;

ACUTE CORONARY SYNDROME; ACUTE HEART INFARCTION; AMINOTRANSFERASE BLOOD LEVEL; ARTICLE; ATHEROSCLEROSIS; ATHEROSCLEROTIC PLAQUE; BILIRUBIN BLOOD LEVEL; BRAIN ISCHEMIA; CARDIOVASCULAR DISEASE; CONGESTIVE HEART FAILURE; CORONARY ARTERY DISEASE; CREATININE BLOOD LEVEL; DIABETES MELLITUS; DISEASE COURSE; DISEASE SEVERITY; DOWN REGULATION; DRUG ANTAGONISM; DRUG CONTRAINDICATION; DRUG EFFECT; DRUG ELUTING STENT; DRUG HALF LIFE; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; FOLLOW UP; HEART FAILURE; HEART INFARCTION SIZE; HEART LEFT VENTRICLE ENDSYSTOLIC VOLUME; HEART MUSCLE REVASCULARIZATION; HEART RUPTURE; HEART VENTRICLE REMODELING; HEMOGLOBIN BLOOD LEVEL; HUMAN; INJECTION SITE ERYTHEMA; INJECTION SITE REACTION; LOADING DRUG DOSE; META ANALYSIS (TOPIC); MORTALITY; MULTICENTER STUDY (TOPIC); NON ST SEGMENT ELEVATION MYOCARDIAL INFARCTION; NONHUMAN; PATIENT COMPLIANCE; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); RISK BENEFIT ANALYSIS; SECONDARY PREVENTION; SIDE EFFECT; SIGNAL TRANSDUCTION; ST SEGMENT ELEVATION MYOCARDIAL INFARCTION; SURVIVAL; THROMBOSIS; TREATMENT DURATION;

ANTIBODIES, MONOCLONAL; ANTIBODIES, MONOCLONAL, HUMANIZED; CARDIOVASCULAR DISEASES; HUMANS; INTERLEUKIN 1 RECEPTOR ANTAGONIST PROTEIN; INTERLEUKIN-1; RANDOMIZED CONTROLLED TRIALS AS TOPIC; RECOMBINANT FUSION PROTEINS; SECONDARY PREVENTION; TREATMENT OUTCOME;

EID: 84863459500     PISSN: 11738804     EISSN: 1179190X     Source Type: Journal    
DOI: 10.2165/11631570-000000000-00000     Document Type: Article

References (106)

1. Roger VL, Go AS, Lloyd-Jones DM, et al., American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics - 2011 update: A report from the American Heart Association. Circulation 2011; 123: E18-209
2. O'Keefe JH, Carter MD, Lavie CJ. Primary and secondary prevention of cardiovascular diseases: A practical evidence-based approach. Mayo Clin Proc 2009; 84: 741-757
3. Velagaleti RS, Pencina MJ, Murabito JM, et al. Long-term trends in the incidence of heart failure after myocardial infarction. Circulation 2008; 118: 2057-2062
4. Libby P. The interface of atherosclerosis and thrombosis: Basic mechanisms. Vasc Med 1998; 3 (3): 225-9
5. Franco M, Cooper RS, Bilal U, et al. Challenges and opportunities for cardiovascular disease prevention. Am J Med 2011 Feb; 124 (2): 95-102
6. Ross R. Atherosclerosis-An inflammatory disease. N Engl J Med 1999; 340: 115-126
7. Luster AD. Chemokines - chemotactic cytokines that mediate inflammation. N Engl J Med 1998; 338: 436-445
8. Dinarello CA. Interleukin-1 in the pathogenesis and treatment of inflammatory diseases. Blood 2011; 117: 3720-3732
9. Stutz A, Golenbock D, Latz E. Inflammasomes: Too big to miss. J Clin Invest 2009; 119: 3502-3511
10. Duewell P, Kono H, Rayner KJ, et al. NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals. Nature 2010; 464: 1357-1361
11. Rajamäki K, Lappalainen J, Oörni K, et al. Cholesterol crystals activate the NLRP3 inflammasome in human macrophages: A novel link between cholesterol metabolism and inflammation. PLoS ONE 2010; 5: E11765
12. Chamberlain J, Francis S, Brookes Z, et al. Interleukin-1 regulates multiple atherogenic mechanisms in response to fat feeding. PLoS ONE 2009; 4: E5073
13. Fernandes-Alnemri T, Wu J, Yu JW, et al. The pyroptosome: A supramolecular assembly of ASC dimmers mediating inflammatory cell death via caspase-1 activation. Cell Death Diff 2007; 14: 1590-1604
14. Maseri A, Fuster V. Is there a vulnerable plaque? Circ 2003; 107: 2068-2071
15. Schaar JA, Muller JE, Falk E, et al. Terminology for high-risk and vulnerable coronary artery plaques. Report of a meeting on the vulnerable plaque, June 17 and 18, 2003, Santorini, Greece. Eur Heart J 2004; 25: 1077-1082
16. Abbate A, Bonanno E, Mauriello A, et al. Widespread myocardial inflammation and infarct-related artery patency. Circulation 2004; 110: 46-50
17. Abbate A, Bussani R, Liuzzo G, et al. Sudden coronary death, fatal acute myocardial infarction and widespread coronary and myocardial inflammation. Heart 2008; 94: 737-742
18. Dewberry R, Holden H, Crossman D, et al. Interleukin-1 receptor antagonist expression in human endothelial cells and atherosclerosis. Arterioscler Thromb Vasc Biol 2000; 20: 2394-2400
19. Chamberlain J, Evans D, King A, et al. Interleukin-1beta and signaling of interleukin-1 in vascular wall and circulating cells modulates the extent of neointima formation in mice. Am J Pathol 2006; 168: 1396-1403
20. Isoda K, Sawada S, Ishigami N, et al. Lack of interleukin-1 receptor antagonist modulates plaque composition in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol 2004; 24: 1068-1073
21. Bhaskar V, Yin J, Mirza AM, et al. Monoclonal antibodies targeting IL-1 beta reduce biomarkers of atherosclerosis in vitro and inhibit atherosclerotic plaque formation in apolipoprotein E-deficient mice. Atherosclerosis 2011; 216: 313-320
22. Chamberlain J, Gunn J, Francis S, et al. Temporal and spatial distribution of interleukin-1 beta in balloon injured porcine coronary arteries. Cardiovasc Res 1999; 44: 156-165
23. Alexander MR, Moehle CW, Johnson JL, et al. Genetic inactivation of IL-1 signaling enhances atherosclerotic plaque instability and reduces outward vessel remodeling in advanced atherosclerosis in mice. J Clin Invest 2012; 122 (1): 70-9
24. Bevilacqua MP, Pober JS, Majeau GR, et al. Interleukin 1 (IL-1) induces biosynthesis and cell surface expression of procoagulant activity in human vascular endothelial cells. J Exp Med 1984; 160: 618-623
25. Donath MY, Shoelson SE. Type 2 diabetes as an inflammatory disease. Nat Rev Immunol 2011; 11: 98-107
26. Libby P, Ridker PM, Maseri A. Inflammation and atherosclerosis. Circ 2002; 105: 1135-1143
27. Liuzzo G, Biasucci LM, Gallimore JR, et al. The prognostic value of C-reactive protein and serum amyloid a protein in severe unstable angina. N Engl J Med 1994; 331: 417-424
28. Abbate A, Biondi-Zoccai GG, Brugaletta S, et al. C-reactive protein and other inflammatory biomarkers as predictors of outcome following acute coronary syndromes. Semin Vasc Med 2003; 3: 375-384
29. Biasucci LM, Bellocci F, Landolina M, et al. Risk stratification of ischaemic patients with implantable cardioverter defibrillators by C-reactive protein and a multi-markers strategy: Results of the CAMI-GUIDE study. Eur Heart J. Epub 2012 Jan 26
30. Biasucci LM, CDC; AHA. CDC/AHA Workshop on Markers of Inflammation and Cardiovascular Disease: Application to Clinical and Public Health Practice: Clinical use of inflammatory markers in patients with cardiovascular diseases: A background paper. Circulation 2004; 110: E560-7
31. Ridker PM, Cushman M, Stampfer MJ, et al. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men.NEngl J Med 1997; 336: 973-9
32. Ridker PM, Hennekens CH, Buring JE, et al. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med 2000; 342: 836-843
33. Ridker PM, Rifai N, Clearfield M, et al., Air Force/Texas Coronary Atherosclerosis Prevention Study Investigators. Measurement of C-reactive protein for the targeting of statin therapy in the primary prevention of acute coronary events. N Engl J Med 2001; 344: 1959-1965
34. Emerging Risk Factors Collaboration, Kaptoge S, Di Angelantonio E, et al. C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: An individual participant meta-Analysis. Lancet 2010; 375: 132-140
35. Ikonomidis I, Andreotti F, Economou E, et al. Increased proinflammatory cytokines in patients with chronic stable angina and their reduction by aspirin. Circulation 1999; 100: 793-8
36. Saitoh T, Kishida H, Tsukada Y, et al. Clinical significance of increased plasma concentration of macrophage colony-stimulating factor in patients with angina pectoris. J Am Coll Cardiol 2000; 35: 655-665
37. Ikonomidis I, Lekakis J, Revela I, et al. Increased circulating C-reactive protein and macrophage-colony stimulating factor are complementary predictors of long-term outcome in patients with chronic coronary artery disease. Eur Heart J 2005 Aug; 26 (16): 1618-1624
38. Kilic T, Ural D, Ural E, et al. Relation between proinflammatory to antiinflammatory cytokine ratios and long-term prognosis in patients with non-ST elevation acute coronary syndrome. Heart 2006; 92: 1041-6
39. Correia LC, Andrade BB, Borges VM, et al. Prognostic value of cytokines and chemokines in addition to the GRACE Score in non-ST-elevation acute coronary syndromes. Clin Chim Acta 2010; 411: 540-5
40. Biasucci LM, Liuzzo G, Fantuzzi G, et al. Increasing levels of interleukin (IL)-1Ra and IL-6 during the first 2 days of hospitalization in unstable angina are associated with increased risk of in-hospital coronary events. Circulation 1999; 99: 2079-84
41. Patti G, Di Sciascio G, D'Ambrosio A, et al. Prognostic value of interleukin-1 receptor antagonist in patients undergoing percutaneous coronary intervention. Am J Cardiol 2002; 89: 372-6
42. Biasucci LM, Vitelli A, Liuzzo G, et al. Elevated levels of interleukin-6 in unstable angina. Circulation 1996 Sep 1; 94 (5): 874-7
43. Kohli P, Bonaca MP, Kakkar R, et al. Role of ST2 in non-ST-elevation acute coronary syndrome in the MERLIN-TIMI 36 trial. Clin Chem 2012; 58: 257-266
44. Ikonomidis I, Lekakis JP, Nikolaou M, et al. Inhibition of interleukin-1 by anakinra improves vascular and left ventricular function in patients with rheumatoid arthritis. Circulation 2008; 117: 2662-9
45. Ikonomidis I, Tzortzis S, Lekakis J, et al. Lowering interleukin-1 activity with anakinra improves myocardial deformation in rheumatoid arthritis. Heart 2009; 95: 1502-7
46. Ikonomidis I, Tzortzis S, Lekakis J, et al. Association of soluble apoptotic markers with impaired left ventricular deformation in patients with rheumatoid arthritis: Effects of inhibition of interleukin-1 activity by anakinra. Thromb Haemost 2011; 106: 959-967
47. Biasucci LM, Liuzzo G, Grillo RL, et al. Elevated levels of C-reactive protein at discharge in patients with unstable angina predict recurrent instability. Circulation 1999; 99: 855-860
48. Ridker PM, Cannon CP, Morrow D, et al. Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 (PROVE IT-TIMI 22) Investigators. C-reactive protein levels and outcomes after statin therapy. N Engl J Med 2005; 352: 20-8
49. Versaci F, Gaspardone A, Tomai F, et al. Immunosuppressive Therapy for the Prevention of Restenosis after Coronary Artery Stent Implantation (IMPRESS Study). J Am Coll Cardiol 2002; 40: 1935-1942
50. Ribichini F, Tomai F, Ferrero V, et al. Immunosuppressive oral prednisone after percutaneous interventions in patients with multi-vessel coronary artery disease: The IMPRESS-2/MVDstudy. EuroIntervention 2005; 1: 173-180
51. Ridker PM, Danielson E, Fonseca FA, et al., JUPITER Study Group. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med 2008; 359: 2195-2207
52. Cristell N, Cianflone D, Durante A, et al., FAMI Study Investigators. Highsensitivity C-reactive protein is within normal levels at the very onset of first ST-segment elevation acute myocardial infarction in 41% of cases: A multiethnic case-control study. J Am Coll Cardiol 2011; 58: 2654-2661
53. Giugliano GR, Giugliano RP, Gibson CM, et al. Meta-Analysis of corticosteroid treatment in acute myocardial infarction. Am J Cardiol 2003; 91: 1055-9
54. Antman EM, Anbe DT, Armstrong PW, et al., American College of Cardiology; American Heart Association Task Force on Practice Guidelines; Canadian Cardiovascular Society. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1999 Guidelines for the Management of Patients with Acute Myocardial Infarction). Circulation 2004 Aug 31; 110 (9): E82-292
55. Altman R, Luciardi HL, Muntaner J, et al. Efficacy assessment of meloxicam, a preferential cyclooxygenase-2 inhibitor, in acute coronary syndromes without ST-segment elevation: The Nonsteroidal Anti-Inflammatory Drugs in Unstable Angina Treatment-2 (NUT-2) pilot study. Circulation 2002; 106: 191-5
56. Bogaty P, Brophy JM, Noel M, et al. Impact of prolonged cyclooxygenase-2 inhibition on inflammatory markers and endothelial function in patients with ischemic heart disease and raised C-reactive protein: A randomized placebo-controlled study. Circulation 2004; 110: 934-9
57. Mukherjee D, Nissen SE, Topol EJ. Risk of cardiovascular events associated with selective COX-2 inhibitors. JAMA 2001; 286 (8): 954-9
58. Brown DL, DesaiKK, Vakili BA, et al. Clinical and biochemical results of the metalloproteinase inhibition with subantimicrobial doses of doxycycline to prevent acute coronary syndromes (MIDAS) pilot trial. Arterioscler Thromb Vasc Biol 2004; 24: 733-8
59. Fernandes JL, De Oliveira RT, Mamoni RL, et al. Pentoxifylline reduces proinflammatory and increases anti-inflammatory activity in patients with coronary artery disease: A randomized placebo-controlled study. Atherosclerosis 2008; 196: 434-442
60. Ridker PM. Testing the inflammatory hypothesis of atherothrombosis: Scientific rationale for the cardiovascular inflammation reduction trial (CIRT). J Thromb Haemost 2009 Jul; 7 Suppl. 1: 332-9
61. Curtis JR, Singh JA. Use of biologics in rheumatoid arthritis: Current and emerging paradigms of care. Clin Ther 2011 Jun; 33 (6): 679-707
62. Wallis RS. Tumour necrosis factor antagonists: Structure, function, and tuberculosis risks. Lancet Infect Dis 2008 Oct; 8 (10): 601-611
63. Padfield GJ, Din JN, Mills NL, et al. Cardiovascular effects of tumor necrosis factor alpha antagonism in patients with acute myocardial infarction. J Am Coll Cardiol 2010; 55: A102.E952
64. Mann DL, McMurray JJ, Packer M, et al. Targeted anticytokine therapy in patients with chronic heart failure: Results of the Randomized Etanercept Worldwide Evaluation (RENEWAL). Circulation 2004; 109: 1594-1602
65. Chung ES, Packer M, Lo KH, et al., 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: 3133-3140
66. Deswal A, Bozkurt B, Seta Y, et al. Safety and efficacy of a soluble P75 tumor necrosis factor receptor (Enbrel, etanercept) in patients with advanced heart failure. Circulation 1999; 99 (25): 3224-6
67. Mann DL. Targeted anticytokine therapy and the failing heart. Am J Cardiol 2005; 95 (11A): 9C-16C 68.
68. Scallon BJ, Moore MA, Trinh H, et al. Chimeric anti-TNF-Alpha monoclonal antibody cA2 binds recombinant transmembrane TNF-Alpha and activates immune effector functions. Cytokine 1995; 7: 251-259
69. Furst DE. Anakinra: Review of recombinant human interleukin-I receptor antagonist in the treatment of rheumatoid arthritis. Clin Ther 2004; 26: 1960-1975
70. Dinarello CA. Blocking interleukin-1b in acute and chronic autoinflammatory diseases. J Intern Med 2011; 269: 16-28
71. Crossman DC, Morton AC, Gunn JP, et al. Investigation of the effect of interleukin-1 receptor antagonist (IL-1ra) on markers of inflammation in non-ST elevation acute coronary syndromes (The MRC-ILA-HEART Study). Trials 2008; 9: 8
72. Morton AC, Foley CE, Rothman A, et al. Investigation of IL-1 inhibition in patients presenting witih non-ST elevation myocardial infarction acute coronary syndromes (The MRC-ILA-HEART study) [abstract]. Heart 2011; 97: A13
73. Abbate A, Kontos MC, Grizzard JD, et al., VCU-ART Investigators. 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: 1371-7
74. Abbate A, Salloum FN, Vecile E, et al. Anakinra, a recombinant human interleukin-1 receptor antagonist, inhibits apoptosis in experimental acute myocardial infarction. Circulation 2008; 117: 2670-2683
75. Mezzaroma E, Toldo S, Farkas D, et al. The inflammasome promotes adverse cardiac remodeling following acute myocardial infarction in the mouse. Proc Natl Acad Sci U S A 2011; 108: 19725-30
76. Abbate A, Salloum FN, Van Tassell BW, et al. Alterations in the interleukin-1/interleukin-1 receptor antagonist balance modulate cardiac remodeling following myocardial infarction in the mouse. PLoS ONE 2011; 6: E27923
77. Van Tassell BW, Varma A, Salloum FN, et al. Interleukin-1 trap attenuates cardiac remodeling after experimental acute myocardial infarction in mice. J Cardiovasc Pharmacol 2010; 55: 117-122
78. Abbate A, Van Tassell BW, Seropian IM, et al. Interleukin-1beta modulation using a genetically engineered antibody prevents adverse cardiac remodelling following acute myocardial infarction in the mouse. Eur J Heart Fail 2010; 12: 319-322
79. Van Tassell BW, Seropian IM, Toldo S, et al. Pharmacologic inhibition of myeloid differentiation factor 88 (MyD88) prevents left ventricular dilation and hypertrophy after experimental acute myocardial infarction in the mouse. J Cardiovasc Pharmacol 2010; 55: 385-390
80. Van Tassell BW, Bhardwaj HL, Grizzard JD, et al. Right ventricular systolic dysfunction in patients with reperfused ST-segment elevation acute myocardial infarction. Int J Cardiol 2012 Mar 8; 155 (2): 314-6
81. Van Tassell BW, Arena RA, Toldo S, et al. Enhanced Interleukin-1 activity contributes to exercise intolerance in patients with systolic heart failure. PLoS One 2012; 7: E33438
82. Ridker PM, Thuren T, Zalewski A, et al. Interleukin-1b inhibition and the prevention of recurrent cardiovascular events: Rationale and design of the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS). Am Heart J 2011; 162: 597-605
83. Stroemer RP, Rothwell NJ. Cortical protection by localized striatal injection of IL-1ra following cerebral ischemia in the rat. J Cereb Blood Flow Metab 1997; 17: 597-604
84. Emsley HC, Smith CJ, Georgiou RF, et al., Acute Stroke Investigators. A randomised phase II study of interleukin-1 receptor antagonist in acute stroke patients. J Neurol Neurosurg Psychiatry 2005; 76: 1366-1372
85. Larsen CM, Faulenbach M, Vaag A, et al. Interleukin-1-receptor antagonist in type 2 diabetes mellitus. N Engl J Med 2007; 356: 1517-1526
86. Kineret- (anakinra): US prescribing information. ThousandOaks (CA): Biovitrum AB, 2009 [online]. Available from URL: www.kineretrx.com [Accessed 2011 Dec 31]
87. Fleischmann RM, Schechtman J, Bennett R, et al., for the 990757 Study Group. Anakinra, a recombinant human interleukin-1 receptor antagonist (r-metHuIL-1ra), in patients with rheumatoid arthritis. Arthritis Rheum 2003; 48: 927-934
88. Fleischmann RM, Tesser J, Schiff MH, et al. Safety of extended treatment with anakinra in patients with rheumatoid arthritis. Ann Rheum Dis 2006; 65: 1006-1012
89. Fisher Jr CJ, Dhainaut JF, Opal SM, et al., Phase III rhIL-1ra Sepsis Syndrome Study Group. Recombinant human interleukin 1 receptor antagonist in the treatment of patients with sepsis syndrome: Results from a randomized, double-blind, placebo-controlled trial. JAMA 1994; 271: 1836-1843
90. Opal SM, Fisher Jr CJ, Dhinainaut JF, et al., The Interleukin-1 Receptor Antagonist Sepsis Investigator Group. Confirmatory interleukin-1 receptor antagonist trial in severe sepsis: A phase III, randomized, double-blind, placebo-controlled, multicenter trial. Crit Care Med 1997; 25: 1115-1124
91. Fisher Jr CJ, Agosti JM, Opal SM, et al., The Soluble TNF Receptor Sepsis Study Group. Treatment of septic shock with the tumor necrosis factor receptor: Fc fusion protein. N Engl J Med 1996; 334: 1697-1702
92. Curran MP. Canakinumab: In patients with cryopyrin-Associated periodic syndromes. BioDrugs 2012; 26 (1): 53-9
93. Ilaris- (canakinumab): US prescribing information. East Hanover (NJ): Novartis Pharmaceutical Corp, 2011 [online]. Available from URL: www. ilaris.com [Accessed 2011 Dec 31]
94. Schlesinger N, Mysler E, Lin HY, et al. Canakinumab reduces the risk of acute gouty arthritis flare during initiation of allopurinol treatment: Results of a double-blind randomized study. Ann Rheum Dis 2011; 70: 1264-1271
95. So A, De Meulemeester M, Pikhlak A, et al. Canakinumab for the treatment of acute flares in difficult-to-treat gouty arthritis: Results of a multicenter, phase II, dose-ranging study. Arthritis Rheum 2010; 62: 3064-3076
96. Alten R, Gomez-Reino J, Durez P, et al. Efficacy and safety of the human anti-IL-1beta monoclonal antibody canakinumab in rheumatoid arthritis: Results of a 12-week, phase II, dose-finding study. BMC Musculoskelet Disord 2011; 12: 153-162
97. Stahl N, Radin A, Mellis S. Rilonacept: CAPS and beyond. AnnNYAcad Sci 2009; 1182: 124-134
98. Arcalyst- (rilonacept injection for subcutaneous use): US prescribing information. Tarrytown (NY): Regeneron Pharmaceuticals Inc., 2009 [online]. Available from URL: www.regeneron.com/ARCALYST-fpi.pdf [Accessed 2011 Dec 31]
99. Terkeltaub R, Sundy JS, Schumacher HR, et al. The interleukin 1 inhibitor rilonacept in treatment of chronic gouty arthritis: Results of a placebocontrolled, monosequence crossover, non-randomised, single-blind pilot study. Ann Rheum Dis 2009; 68: 1613-7
100. National Heart, Lung, and Blood Institute (NHLBI). Rilonacept to improve artery function in patients with atherosclerosis [ClinicalTrials.gov identifier NCT00417417]. US National Institutes of Health, Clinical Trials.gov [online]. Available from URL: www.clinicaltrials.gov [Accessed 2011 Dec 31]
101. Geiler J, McDermott MF. Gevokizumab, an anti-IL-1b mAb for the potential treatment of type 1 and 2 diabetes, rheumatoid arthritis and cardiovascular disease. Curr Opin Mol Ther 2010; 12: 755-769
102. Gül A, Tugal-Tutkun I, Dinarello CA, et al. Interleukin-1b- regulating antibody XOMA 052 (gevokizumab) in the treatment of acute exacerbations of resistant uveitis of Behcet's disease: An open-label pilot study. Ann Rheum Dis 2012 Apr; 71 (4): 563-6
103. Roell MK, Issafras H, Bauer RJ, et al. Kinetic approach to pathway attenuation using XOMA 052, a regulatory therapeutic antibody that modulates interleukin-1beta activity. J Biol Chem 2010; 285: 20607-14
104. Owyang AM, Maedler K, Gross L, et al. XOMA 052, an anti-IL-1{beta} monoclonal antibody, improves glucose control and {beta}-cell function in the diet-induced obesity mouse model. Endocrinology 2010; 151: 2515-2527
105. Abbate A, Biondi-ZoccaiGG, Agostoni P, et al. Recurrent angina after coronary revascularization: A clinical challenge. Eur Heart J 2007; 28: 1057-1065
106. Liuzzo G, Angiolillo DJ, Buffon A, et al. Enhanced response of blood monocytes to in vitro lipopolysaccharide-challenge in patients with recurrent unstable angina. Circulation 2001; 103: 2236-2241