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Interleukin (IL)-1 Blocking Compounds and Their Use in Autoinflammatory Diseases

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Textbook of Autoinflammation

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Abstract

Autoinflammatory diseases are driven by an excessive production of proinflammatory cytokines. Hypersecretion of interleukin (IL)-1β plays a pivotal role in the pathogenesis of many of these disorders and explains a large part of the clinical manifestations of these multisystem diseases. Several drugs which block the IL-1 pathway have been developed. In this chapter, we summarize the properties of the three compounds, namely anakinra, rilonacept and canakinumab, which are currently approved for treatment of a variety of autoinflammatory diseases. We focus on their mode of action, summarize the data of their use in autoinflammatory diseases derived from case reports, case series, clinical trials, and registries, outline their pharmacokinetic and pharmacodynamics properties and discuss safety aspects of these medications.

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Abbreviations

ACR:

American College of Rheumatology

ADA:

Anti-drug antibodies

AISLE:

Autoinflammatory syndrome associated with lymphedema

AOSD:

Adult-onset Still disease

AP1S3:

Adaptor related protein complex 1 sigma 3

APLAID:

Autoinflammation and PLCG2-associated antibody deficiency and immune dysregulation

AUC:

Area under the curve

CAPS:

Cryopyrin-associated periodic syndrome

CARD:

Caspase recruitment domain

CNS:

Central nervous system

CSF:

Cerebrospinal fluid

DADA2:

Deficiency of adenosine deaminase 2

DIRA:

Deficiency of the IL-1 receptor antagonist

DITRA:

Deficiency of the IL-36 receptor antagonist

DMARD:

Disease modifying antirheumatic drugs

EMA:

European Medicines Agency

ESRD:

End-stage renal disease

FDA:

Food and Drug Administration

FMF:

Familial Mediterranean fever

HOIL:

Heme-oxidized iron regulatory protein 2 ubiquitin ligase-1

IC50:

50% inhibitory concentration

IL:

Interleukin

IL-1Ra:

Interleukin-1 receptor antagonist

IL-1R-AcP:

IL-1 receptor accessory protein

LPS:

Lipopolysaccharide

MAS:

Macrophage activation syndrome

MKD:

Mevalonate kinase deficiency

MTX:

Methotrexate

NLR:

NOD-like receptor

NOMID:

Neonatal onset multisystem inflammatory disease

PAAND:

Pyrin-associated autoinflammation with neutrophilic dermatosis

PAPA:

Pyogenic arthritis, pyoderma gangrenosum and acne

PFAPA:

Periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis

PFIT:

Periodic fever, immunodeficiency, and thrombocytopenia

RA:

Rheumatoid arthritis

SAPHO:

Synovitis, acne, pustulosis, hyperostosis, osteitis

SIFD:

Sideroblastic anemia with immunodeficiency, fevers, and developmental delay

sJIA:

Systemic juvenile idiopathic arthritis

SOBI:

Swedish Orphan Biovitrum

TNFRSF:

TNF receptor superfamily member

TRAP:

Target-related affinity profiling

TRAPS:

Tumor necrosis factor receptor-associated periodic syndrome

References

  1. Dinarello CA, Simon A, van der Meer JW. Treating inflammation by blocking interleukin-1 in a broad spectrum of diseases. Nat Rev Drug Discov. 2012;11:633–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Balavoine JF, de Rochemonteix B, Williamson K, Seckinger P, Cruchaud A, Dayer JM. Prostaglandin E2 and collagenase production by fibroblasts and synovial cells is regulated by urine-derived human interleukin 1 and inhibitor(s). J Clin Invest. 1986;78:1120–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Eisenberg SP, Evans RJ, Arend WP, et al. Primary structure and functional expression from complementary DNA of a human interleukin-1 receptor antagonist. Nature. 1990;343:341–6.

    Article  CAS  PubMed  Google Scholar 

  4. Stahl S, Gräslund T, Eriksson Karlström A, Frejd FY, Nygren PÅ, Löfblom J. Affibody molecules in biotechnological and medical applications. Trends Biotechnol. 2017;35:691–712.

    Article  PubMed  CAS  Google Scholar 

  5. Arend WP. Cytokine imbalance in the pathogenesis of rheumatoid arthritis: the role of interleukin-1 receptor antagonist. Semin Arthritis Rheum. 2001;30:1–6.

    Article  CAS  PubMed  Google Scholar 

  6. Arend WP, Welgus HG, Thompson RC, Eisenberg SP. Biological properties of recombinant human monocyte-derived interleukin 1 receptor antagonist. J Clin Invest. 1990;85:1694–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Seckinger P, Yaron I, Meyer FA, Yaron M, Dayer JM. Modulation of the effects of interleukin-1 on glycosaminoglycan synthesis by the urine-derived interleukin-1 inhibitor, but not by interleukin-6. Arthritis Rheum. 1990;33:1807–14.

    Article  CAS  PubMed  Google Scholar 

  8. Seckinger P, Kaufmann MT, Dayer JM. An interleukin 1 inhibitor affects both cell-associated interleukin 1-induced T cell proliferation and PGE2/collagenase production by human dermal fibroblasts and synovial cells. Immunobiology. 1990;180:316–27.

    Article  CAS  PubMed  Google Scholar 

  9. Smith RJ, Chin JE, Sam LM, Justen JM. Biologic effects of an interleukin-1 receptor antagonist protein on interleukin-1-stimulated cartilage erosion and chondrocyte responsiveness. Arthritis Rheum. 1991;34:78–83.

    Article  CAS  PubMed  Google Scholar 

  10. Seckinger P, Klein-Nulend J, Alander C, Thompson RC, Dayer JM, Raisz LG. Natural and recombinant human IL-1 receptor antagonists block the effects of IL-1 on bone resorption and prostaglandin production. J Immunol. 1990;145:4181–4.

    CAS  PubMed  Google Scholar 

  11. Schwab JH, Anderle SK, Brown RR, Dalldorf FG, Thompson RC. Pro- and anti-inflammatory roles of interleukin-1 in recurrence of bacterial cell wall-induced arthritis in rats. Infect Immun. 1991;59:4436–42.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Matsukawa A, Ohkawara S, Maeda T, Takagi K, Yoshinaga M. Production of IL-1 and IL-1 receptor antagonist and the pathological significance in lipopolysaccharide-induced arthritis in rabbits. Clin Exp Immunol. 1993;93:206–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Wooley PH, Whalen JD, Chapman DL, et al. The effect of an interleukin-1 receptor antagonist protein on type II collagen-induced arthritis and antigen-induced arthritis in mice. Arthritis Rheum. 1993;36:1305–14.

    Article  CAS  PubMed  Google Scholar 

  14. Arner EC, Harris RR, DiMeo TM, Collins RC, Galbraith W. Interleukin-1 receptor antagonist inhibits proteoglycan breakdown in antigen induced but not polycation induced arthritis in the rabbit. J Rheumatol. 1995;22:1338–46.

    CAS  PubMed  Google Scholar 

  15. Lewthwaite J, Blake SM, Hardingham TE, Warden PJ, Henderson B. The effect of recombinant human interleukin 1 receptor antagonist on the induction phase of antigen induced arthritis in the rabbit. J Rheumatol. 1994;21:467–72.

    CAS  PubMed  Google Scholar 

  16. Carter DB, Deibel MR Jr, Dunn CJ, et al. Purification, cloning, expression and biological characterization of an interleukin-1 receptor antagonist protein. Nature. 1990;344:633–8.

    Article  CAS  PubMed  Google Scholar 

  17. Mertens M, Singh JA. Anakinra for rheumatoid arthritis. Cochrane Database Syst Rev. 2009;CD005121.

    Google Scholar 

  18. Mertens M, Singh JA. Anakinra for rheumatoid arthritis: a systematic review. J Rheumatol. 2009;36:1118–25.

    Article  CAS  PubMed  Google Scholar 

  19. Thaler K, Chandiramani DV, Hansen RA, Gartlehner G. Efficacy and safety of anakinra for the treatment of rheumatoid arthritis: an update of the Oregon drug effectiveness review project. Biologics. 2009;3:485–98.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Akar S, Cetin P, Kalyoncu U, et al. A nationwide experience with the off-label use of interleukin-1 targeting treatment in familial Mediterranean fever patients. Arthritis Care Res (Hoboken). 2017;70:1090–4.

    Article  CAS  Google Scholar 

  21. Ben-Zvi I, Kukuy O, Giat E, et al. Anakinra for colchicine-resistant familial Mediterranean fever: a randomized, double-blind, placebo-controlled trial. Arthritis Rheumatol. 2017;69:854–62.

    Article  CAS  PubMed  Google Scholar 

  22. Bodar EJ, Kuijk LM, Drenth JP, van der Meer JW, Simon A, Frenkel J. On-demand anakinra treatment is effective in mevalonate kinase deficiency. Ann Rheum Dis. 2011;70:2155–8.

    Article  CAS  PubMed  Google Scholar 

  23. Bodar EJ, van der Hilst JC, Drenth JP, van der Meer JW, Simon A. Effect of etanercept and anakinra on inflammatory attacks in the hyper-IgD syndrome: introducing a vaccination provocation model. Neth J Med. 2005;63:260–4.

    CAS  PubMed  Google Scholar 

  24. Gattorno M, Pelagatti MA, Meini A, et al. Persistent efficacy of anakinra in patients with tumor necrosis factor receptor-associated periodic syndrome. Arthritis Rheum. 2008;58:1516–20.

    Article  CAS  PubMed  Google Scholar 

  25. Simon A, Bodar EJ, van der Hilst JC, et al. Beneficial response to interleukin 1 receptor antagonist in traps. Am J Med. 2004;117:208–10.

    Article  CAS  PubMed  Google Scholar 

  26. Obici L, Meini A, Cattalini M, et al. Favourable and sustained response to anakinra in tumour necrosis factor receptor-associated periodic syndrome (TRAPS) with or without AA amyloidosis. Ann Rheum Dis. 2011;70:1511–2.

    Article  CAS  PubMed  Google Scholar 

  27. Lovell DJ, Bowyer SL, Solinger AM. Interleukin-1 blockade by anakinra improves clinical symptoms in patients with neonatal-onset multisystem inflammatory disease. Arthritis Rheum. 2005;52:1283–6.

    Article  CAS  PubMed  Google Scholar 

  28. Goldbach-Mansky R, Dailey NJ, Canna SW, et al. Neonatal-onset multisystem inflammatory disease responsive to interleukin-1beta inhibition. N Engl J Med. 2006;355:581–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Kullenberg T, Lofqvist M, Leinonen M, Goldbach-Mansky R, Olivecrona H. Long-term safety profile of anakinra in patients with severe cryopyrin-associated periodic syndromes. Rheumatology. 2016;55:1499–506.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Hawkins PN, Lachmann HJ, McDermott MF. Interleukin-1-receptor antagonist in the Muckle-Wells syndrome. N Engl J Med. 2003;348:2583–4.

    Article  PubMed  Google Scholar 

  31. Hoffman HM, Rosengren S, Boyle DL, et al. Prevention of cold-associated acute inflammation in familial cold autoinflammatory syndrome by interleukin-1 receptor antagonist. Lancet. 2004;364:1779–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Arostegui JI, Arnal C, Merino R, et al. NOD2 gene-associated pediatric granulomatous arthritis: clinical diversity, novel and recurrent mutations, and evidence of clinical improvement with interleukin-1 blockade in a Spanish cohort. Arthritis Rheum. 2007;56:3805–13.

    Article  CAS  PubMed  Google Scholar 

  33. Dierselhuis MP, Frenkel J, Wulffraat NM, Boelens JJ. Anakinra for flares of pyogenic arthritis in PAPA syndrome. Rheumatology. 2005;44:406–8.

    Article  CAS  PubMed  Google Scholar 

  34. Brenner M, Ruzicka T, Plewig G, Thomas P, Herzer P. Targeted treatment of pyoderma gangrenosum in PAPA (pyogenic arthritis, pyoderma gangrenosum and acne) syndrome with the recombinant human interleukin-1 receptor antagonist anakinra. Br J Dermatol. 2009;161:1199–201.

    Article  CAS  PubMed  Google Scholar 

  35. Herlin T, Fiirgaard B, Bjerre M, et al. Efficacy of anti-IL-1 treatment in Majeed syndrome. Ann Rheum Dis. 2013;72:410–3.

    Article  CAS  PubMed  Google Scholar 

  36. Schnellbacher C, Ciocca G, Menendez R, et al. Deficiency of interleukin-1 receptor antagonist responsive to anakinra. Pediatr Dermatol. 2013;30:758–60.

    Article  PubMed  Google Scholar 

  37. Aksentijevich I, Masters SL, Ferguson PJ, et al. An autoinflammatory disease with deficiency of the interleukin-1-receptor antagonist. N Engl J Med. 2009;360:2426–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Reddy S, Jia S, Geoffrey R, et al. An autoinflammatory disease due to homozygous deletion of the IL1RN locus. N Engl J Med. 2009;360:2438–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Rossi-Semerano L, Piram M, Chiaverini C, De Ricaud D, Smahi A, Koné-Paut I. First clinical description of an infant with interleukin-36-receptor antagonist deficiency successfully treated with anakinra. Pediatrics. 2013;132:e1043–7.

    Article  PubMed  Google Scholar 

  40. Tauber M, Viguier M, Le Gall C, Smahi A, Bachelez H. Is it relevant to use an interleukin-1-inhibiting strategy for the treatment of patients with deficiency of interleukin-36 receptor antagonist? Br J Dermatol. 2014;170:1198–9.

    Article  CAS  PubMed  Google Scholar 

  41. Huffmeier U, Watzold M, Mohr J, Schon MP, Mossner R. Successful therapy with anakinra in a patient with generalized pustular psoriasis carrying IL36RN mutations. Br J Dermatol. 2014;170:202–4.

    Article  CAS  PubMed  Google Scholar 

  42. Di Zazzo A, Tahvildari M, Florakis GJ, Dana R. Ocular manifestations of inherited phospholipase-cgamma2-associated antibody deficiency and immune dysregulation. Cornea. 2016;35:1656–7.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Canna SW, de Jesus AA, Gouni S, et al. An activating NLRC4 inflammasome mutation causes autoinflammation with recurrent macrophage activation syndrome. Nat Genet. 2014;46:1140–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Masters SL, Lagou V, Jéru I, et al. Familial autoinflammation with neutrophilic dermatosis reveals a regulatory mechanism of pyrin activation. Sci Transl Med. 2016;8:332ra345.

    Article  CAS  Google Scholar 

  45. Volker-Touw CM, de Koning HD, Giltay JC, et al. Erythematous nodes, urticarial rash and arthralgias in a large pedigree with NLRC4-related autoinflammatory disease, expansion of the phenotype. Br J Dermatol. 2017;176:244–8.

    Article  CAS  PubMed  Google Scholar 

  46. Stojanov S, Lapidus S, Chitkara P, et al. Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) is a disorder of innate immunity and Th1 activation responsive to IL-1 blockade. Proc Natl Acad Sci U S A. 2011;108:7148–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Cantarini L, Vitale A, Galeazzi M, Frediani B. A case of resistant adult-onset periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome responsive to anakinra. Clin Exp Rheumatol. 2012;30:593.

    PubMed  Google Scholar 

  48. Pardeo M, Pires Marafon D, Messia V, Garganese MC, De Benedetti F, Insalaco A. Anakinra in a cohort of children with chronic nonbacterial osteomyelitis. J Rheumatol. 2017;44:1231–8.

    Article  PubMed  Google Scholar 

  49. Wendling D, Prati C, Aubin F. Anakinra treatment of SAPHO syndrome: short-term results of an open study. Ann Rheum Dis. 2012;71:1098–100.

    Article  CAS  PubMed  Google Scholar 

  50. Vastert SJ, de Jager W, Noordman BJ, et al. Effectiveness of first-line treatment with recombinant interleukin-1 receptor antagonist in steroid-naive patients with new-onset systemic juvenile idiopathic arthritis: results of a prospective cohort study. Arthritis Rheumatol. 2014;66:1034–43.

    Article  CAS  PubMed  Google Scholar 

  51. Dewitt EM, Kimura Y, Beukelman T, et al. Consensus treatment plans for new-onset systemic juvenile idiopathic arthritis. Arthritis Care Res (Hoboken). 2012;64:1001–10.

    CAS  Google Scholar 

  52. Pardeo M, Pires Marafon D, Insalaco A, et al. Anakinra in systemic juvenile idiopathic arthritis: a single-center experience. J Rheumatol. 2015;42:1523–7.

    Article  CAS  PubMed  Google Scholar 

  53. Quartier P, Allantaz F, Cimaz R, et al. A multicentre, randomised, double-blind, placebo-controlled trial with the interleukin-1 receptor antagonist anakinra in patients with systemic-onset juvenile idiopathic arthritis (ANAJIS trial). Ann Rheum Dis. 2011;70:747–54.

    Article  CAS  PubMed  Google Scholar 

  54. Horneff G, Schulz AC, Klotsche J, et al. Experience with etanercept, tocilizumab and interleukin-1 inhibitors in systemic onset juvenile idiopathic arthritis patients from the BIKER registry. Arthritis Res Ther. 2017;19:256.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. Woerner A, Uettwiller F, Melki I, et al. Biological treatment in systemic juvenile idiopathic arthritis: achievement of inactive disease or clinical remission on a first, second or third biological agent. RMD Open. 2015;1:e000036.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Hong D, Yang Z, Han S, Liang X, Kuifen MA, Zhang X. Interleukin 1 inhibition with anakinra in adult-onset Still disease: a meta-analysis of its efficacy and safety. Drug Des Devel Ther. 2014;8:2345–57.

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Nordstrom D, Knight A, Luukkainen R, et al. Beneficial effect of interleukin 1 inhibition with anakinra in adult-onset Still’s disease. An open, randomized, multicenter study. J Rheumatol. 2012;39:2008–11.

    Article  CAS  PubMed  Google Scholar 

  58. Balasubramaniam G, Parker T, Turner D, et al. Feasibility randomised multicentre, double-blind, double-dummy controlled trial of anakinra, an interleukin-1 receptor antagonist versus intramuscular methylprednisolone for acute gout attacks in patients with chronic kidney disease (ASGARD): protocol study. BMJ Open. 2017;7:e017121.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Ottaviani S, Moltó A, Ea HK, et al. Efficacy of anakinra in gouty arthritis: a retrospective study of 40 cases. Arthritis Res Ther. 2013;15:R123.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  60. Grayson PC, Yazici Y, Merideth M, et al. Treatment of mucocutaneous manifestations in Behcet’s disease with anakinra: a pilot open-label study. Arthritis Res Ther. 2017;19:69.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  61. Fabiani C, Vitale A, Emmi G, et al. Interleukin (IL)-1 inhibition with anakinra and canakinumab in Behcet’s disease-related uveitis: a multicenter retrospective observational study. Clin Rheumatol. 2017;36:191–7.

    Article  PubMed  Google Scholar 

  62. Picco P, Brisca G, Traverso F, Loy A, Gattorno M, Martini A. Successful treatment of idiopathic recurrent pericarditis in children with interleukin-1beta receptor antagonist (anakinra): an unrecognized autoinflammatory disease? Arthritis Rheum. 2009;60:264–8.

    Article  CAS  PubMed  Google Scholar 

  63. Finetti M, Insalaco A, Cantarini L, et al. Long-term efficacy of interleukin-1 receptor antagonist (anakinra) in corticosteroid-dependent and colchicine-resistant recurrent pericarditis. J Pediatr. 2014;164:1425–31.

    Article  CAS  PubMed  Google Scholar 

  64. Vassilopoulos D, Lazaros G, Tsioufis C, Vasileiou P, Stefanadis C, Pectasides D. Successful treatment of adult patients with idiopathic recurrent pericarditis with an interleukin-1 receptor antagonist (anakinra). Int J Cardiol. 2012;160:66–8.

    Article  PubMed  Google Scholar 

  65. Lazaros G, Vasileiou P, Koutsianas C, et al. Anakinra for the management of resistant idiopathic recurrent pericarditis. Initial experience in 10 adult cases. Ann Rheum Dis. 2014;73:2215–7.

    Article  CAS  PubMed  Google Scholar 

  66. Brucato A, Imazio M, Gattorno M, et al. Effect of Anakinra on recurrent pericarditis among patients with colchicine resistance and corticosteroid dependence: the AIRTRIP randomized clinical trial. JAMA. 2016;316:1906–12.

    Article  PubMed  Google Scholar 

  67. Ahn MJ, Yu JE, Jeong J, Sim DW, Koh YI. A case of Schnitzler’s syndrome without monoclonal Gammopathy-associated chronic Urticaria treated with Anakinra. Yonsei Med J. 2018;59:154–7.

    Article  PubMed  Google Scholar 

  68. Sonnichsen A, Saulite I, Mangana J, et al. Interleukin-1 receptor antagonist (anakinra) for Schnitzler syndrome. J Dermatolog Treat. 2016;27:436–8.

    Article  CAS  PubMed  Google Scholar 

  69. Rowczenio DM, Pathak S, Arostegui JI, et al. Molecular genetic investigation, clinical features and response to treatment in 21 patients with Schnitzler’s syndrome. Blood. 2017;131:974–81.

    Article  PubMed  CAS  Google Scholar 

  70. Vanderschueren S, van der Veen A. The Schnitzler syndrome: chronic urticaria in disguise: a single-centre report of 11 cases and a critical reappraisal of the literature. Clin Exp Rheumatol. 2017;35:69–73.

    PubMed  Google Scholar 

  71. Tzanetakou V, Kanni T, Giatrakou S, et al. Safety and efficacy of anakinra in severe hidradenitis suppurativa: a randomized clinical trial. JAMA Dermatol. 2016;152:52–9.

    Article  PubMed  Google Scholar 

  72. Abbate A, Van Tassell BW, Biondi-Zoccai G, et al. Effects of interleukin-1 blockade with anakinra on adverse cardiac remodeling and heart failure after acute myocardial infarction [from the Virginia Commonwealth University-Anakinra remodeling trial (2) (VCU-ART2) pilot study]. Am J Cardiol. 2013;111:1394–400.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Moran A, Bundy B, Becker DJ, et al. Interleukin-1 antagonism in type 1 diabetes of recent onset: two multicentre, randomised, double-blind, placebo-controlled trials. Lancet. 2013;381:1905–15.

    Article  CAS  PubMed  Google Scholar 

  74. Hahn KJ, Ho N, Yockey L, et al. Treatment with Anakinra, a recombinant IL-1 receptor antagonist, unlikely to induce lasting remission in patients with CGD colitis. Am J Gastroenterol. 2015;110:938–9.

    Article  CAS  PubMed  Google Scholar 

  75. Vambutas A, Lesser M, Mullooly V, et al. Early efficacy trial of anakinra in corticosteroid-resistant autoimmune inner ear disease. J Clin Invest. 2014;124:4115–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Galea J, Ogungbenro K, Hulme S, et al. Reduction of inflammation after administration of interleukin-1 receptor antagonist following aneurysmal subarachnoid hemorrhage: results of the subcutaneous interleukin-1Ra in SAH (SCIL-SAH) study. J Neurosurg. 2018;128:515–23.

    Article  PubMed  Google Scholar 

  77. 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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  78. Lust JA, Lacy MQ, Zeldenrust SR, et al. Induction of a chronic disease state in patients with smoldering or indolent multiple myeloma by targeting interleukin 1{beta}-induced interleukin 6 production and the myeloma proliferative component. Mayo Clin Proc. 2009;84:114–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Bresnihan B, Alvaro-Gracia JM, Cobby M, et al. Treatment of rheumatoid arthritis with recombinant human interleukin-1 receptor antagonist. Arthritis Rheum. 1998;41:2196–204.

    Article  CAS  PubMed  Google Scholar 

  80. Cohen S, Hurd E, Cush J, et al. Treatment of rheumatoid arthritis with anakinra, a recombinant human interleukin-1 receptor antagonist, in combination with methotrexate: results of a twenty-four-week, multicenter, randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2002;46:614–24.

    Article  CAS  PubMed  Google Scholar 

  81. Cohen SB, Moreland LW, Cush JJ, et al. A multicentre, double blind, randomised, placebo controlled trial of anakinra (Kineret), a recombinant interleukin 1 receptor antagonist, in patients with rheumatoid arthritis treated with background methotrexate. Ann Rheum Dis. 2004;63:1062–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Fleischmann RM, Schechtman J, Bennett R, et al. Anakinra, a recombinant human interleukin-1 receptor antagonist (r-metHuIL-1ra), in patients with rheumatoid arthritis: a large, international, multicenter, placebo-controlled trial. Arthritis Rheum. 2003;48:927–34.

    Article  CAS  PubMed  Google Scholar 

  83. Garg N, Kasapcopur O, Foster J 2nd, et al. Novel adenosine deaminase 2 mutations in a child with a fatal vasculopathy. Eur J Pediatr. 2014;173:827–30.

    Article  PubMed  Google Scholar 

  84. Zhou Q, Yang D, Ombrello AK, et al. Early-onset stroke and vasculopathy associated with mutations in ADA2. N Engl J Med. 2014;370:911–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. van Montfrans J, Zavialov A, Zhou Q. Mutant ADA2 in vasculopathies. N Engl J Med. 2014;371:478.

    Article  PubMed  Google Scholar 

  86. Jeru I, Hentgen V, Normand S, et al. Role of interleukin-1beta in NLRP12-associated autoinflammatory disorders and resistance to anti-interleukin-1 therapy. Arthritis Rheum. 2011;63:2142–8.

    Article  CAS  PubMed  Google Scholar 

  87. Granowitz EV, Porat R, Mier JW, et al. Pharmacokinetics, safety and immunomodulatory effects of human recombinant interleukin-1 receptor antagonist in healthy humans. Cytokine. 1992;4:353–60.

    Article  CAS  PubMed  Google Scholar 

  88. Fisher CJ Jr, Dhainaut JF, Opal SM, et al. Recombinant human interleukin 1 receptor antagonist in the treatment of patients with sepsis syndrome. Results from a randomized, double-blind, placebo-controlled trial. Phase III rhIL-1ra Sepsis Syndrome Study Group. JAMA. 1994;271:1836–43.

    Article  PubMed  Google Scholar 

  89. Genovese MC, Cohen S, Moreland L, et al. Combination therapy with etanercept and anakinra in the treatment of patients with rheumatoid arthritis who have been treated unsuccessfully with methotrexate. Arthritis Rheum. 2004;50:1412–9.

    Article  CAS  PubMed  Google Scholar 

  90. Li T, Lu WL, Hong HY, et al. Pharmacokinetics and anti-asthmatic potential of non-parenterally administered recombinant human interleukin-1 receptor antagonist in animal models. J Pharmacol Sci. 2006;102:321–30.

    Article  CAS  PubMed  Google Scholar 

  91. Urien S, Bardin C, Bader-Meunier B, et al. Anakinra pharmacokinetics in children and adolescents with systemic-onset juvenile idiopathic arthritis and autoinflammatory syndromes. BMC Pharmacol Toxicol. 2013;14:40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Kim DC, Reitz B, Carmichael DF, Bloedow DC. Kidney as a major clearance organ for recombinant human interleukin-1 receptor antagonist. J Pharm Sci. 1995;84:575–80.

    Article  CAS  PubMed  Google Scholar 

  93. Yang BB, Baughman S, Sullivan JT. Pharmacokinetics of anakinra in subjects with different levels of renal function. Clin Pharmacol Ther. 2003;74:85–94.

    Article  CAS  PubMed  Google Scholar 

  94. Goshen I, Kreisel T, Ounallah-Saad H, et al. A dual role for interleukin-1 in hippocampal-dependent memory processes. Psychoneuroendocrinology. 2007;32:1106–15.

    Article  CAS  PubMed  Google Scholar 

  95. Lepore L, Paloni G, Caorsi R, et al. Follow-up and quality of life of patients with cryopyrin-associated periodic syndromes treated with Anakinra. J Pediatr. 2010;157:310–5.

    Article  PubMed  Google Scholar 

  96. Gutierrez EG, Banks WA, Kastin AJ. Blood-borne interleukin-1 receptor antagonist crosses the blood-brain barrier. J Neuroimmunol. 1994;55:153–60.

    Article  CAS  PubMed  Google Scholar 

  97. Fox E, Jayaprakash N, Pham TH, et al. The serum and cerebrospinal fluid pharmacokinetics of anakinra after intravenous administration to non-human primates. J Neuroimmunol. 2010;223:138–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Clark SR, McMahon CJ, Gueorguieva I, et al. Interleukin-1 receptor antagonist penetrates human brain at experimentally therapeutic concentrations. J Cereb Blood Flow Metab. 2008;28:387–94.

    Article  CAS  PubMed  Google Scholar 

  99. Galea J, Ogungbenro K, Hulme S, et al. Intravenous anakinra can achieve experimentally effective concentrations in the central nervous system within a therapeutic time window: results of a dose-ranging study. J Cereb Blood Flow Metab. 2011;31:439–47.

    Article  CAS  PubMed  Google Scholar 

  100. Greenhalgh AD, Galea J, Denes A, Tyrrell PJ, Rothwell NJ. Rapid brain penetration of interleukin-1 receptor antagonist in rat cerebral ischaemia: pharmacokinetics, distribution, protection. Br J Pharmacol. 2010;160:153–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Gueorguieva I, Clark SR, McMahon CJ, et al. Pharmacokinetic modelling of interleukin-1 receptor antagonist in plasma and cerebrospinal fluid of patients following subarachnoid haemorrhage. Br J Clin Pharmacol. 2008;65:317–25.

    Article  CAS  PubMed  Google Scholar 

  102. Schiff MH, DiVittorio G, Tesser J, et al. The safety of anakinra in high-risk patients with active rheumatoid arthritis: six-month observations of patients with comorbid conditions. Arthritis Rheum. 2004;50:1752–60.

    Article  CAS  PubMed  Google Scholar 

  103. Salliot C, Dougados M, Gossec L. Risk of serious infections during rituximab, abatacept and anakinra treatments for rheumatoid arthritis: meta-analyses of randomised placebo-controlled trials. Ann Rheum Dis. 2009;68:25–32.

    Article  CAS  PubMed  Google Scholar 

  104. Tesser J, Fleischmann R, Dore R, et al. Concomitant medication use in a large, international, multicenter, placebo controlled trial of anakinra, a recombinant interleukin 1 receptor antagonist, in patients with rheumatoid arthritis. J Rheumatol. 2004;31:649–54.

    CAS  PubMed  Google Scholar 

  105. Fleischmann RM, Tesser J, Schiff MH, et al. Safety of extended treatment with anakinra in patients with rheumatoid arthritis. Ann Rheum Dis. 2006;65:1006–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Galloway JB, Hyrich KL, Mercer LK, et al. The risk of serious infections in patients receiving anakinra for rheumatoid arthritis: results from the British Society for Rheumatology Biologics Register. Rheumatology. 2011;50:1341–2.

    Article  PubMed  Google Scholar 

  107. Kuemmerle-Deschner JB, Tyrrell PN, Koetter I, et al. Efficacy and safety of anakinra therapy in pediatric and adult patients with the autoinflammatory Muckle-Wells syndrome. Arthritis Rheum. 2011;63:840–9.

    Article  PubMed  Google Scholar 

  108. Kafka D, Ling E, Feldman G, et al. Contribution of IL-1 to resistance to Streptococcus pneumoniae infection. Int Immunol. 2008;20:1139–46.

    Article  CAS  PubMed  Google Scholar 

  109. Bendele A, Colloton M, Vrkljan M, Morris J, Sabados K. Cutaneous mast cell degranulation in rats receiving injections of recombinant human interleukin-1 receptor antagonist (rhIL-1ra) and/or its vehicle: possible clinical implications. J Lab Clin Med. 1995;125:493–500.

    CAS  PubMed  Google Scholar 

  110. Desai D, Goldbach-Mansky R, Milner JD, et al. Anaphylactic reaction to anakinra in a rheumatoid arthritis patient intolerant to multiple nonbiologic and biologic disease-modifying antirheumatic drugs. Ann Pharmacother. 2009;43:967–72.

    Article  PubMed  PubMed Central  Google Scholar 

  111. Leroy V, Lazaro E, Darrigade AS, Taïeb A, Milpied B, Seneschal J. Successful rapid subcutaneous desensitization to anakinra in a case of delayed-type hypersensitivity reaction. Br J Dermatol. 2016;174:1417–8.

    Article  CAS  PubMed  Google Scholar 

  112. Kaiser C, Knight A, Nordström D, et al. Injection-site reactions upon Kineret (anakinra) administration: experiences and explanations. Rheumatol Int. 2012;32:295–9.

    Article  CAS  PubMed  Google Scholar 

  113. Emmi G, Silvestri E, Cantarini L, et al. Rapid desensitization to anakinra-related delayed reaction: need for a standardized protocol. J Dermatol. 2017;44:981–2.

    Article  PubMed  Google Scholar 

  114. Youngstein T, Hoffmann P, Gül A, et al. International multi-centre study of pregnancy outcomes with interleukin-1 inhibitors. Rheumatology. 2017;56:2102–8.

    Article  PubMed  PubMed Central  Google Scholar 

  115. Venhoff N, Voll RE, Glaser C, Thiel J. IL-1-blockade with anakinra during pregnancy : retrospective analysis of efficacy and safety in female patients with familial Mediterranean fever. Z Rheumatol. 2018;77:127–34.

    Article  CAS  PubMed  Google Scholar 

  116. Smith CJF, Chambers CD. Five successful pregnancies with antenatal anakinra exposure. Rheumatology. 2018;57:1271–5.

    Article  PubMed  PubMed Central  Google Scholar 

  117. Chang Z, Spong CY, Jesus AA, et al. Anakinra use during pregnancy in patients with cryopyrin-associated periodic syndromes (CAPS). Arthritis Rheumatol. 2014;66:3227–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. YY. Prescribing Information Kineret. http://www.kineretrx.com/professional/pi.jsp

  119. XX. Prescribing Information Arcalyst. http://www.regeneron.com/ARCALYST-fpi.pdf

  120. Gillespie J, Mathews R, McDermott MF. Rilonacept in the management of cryopyrin-associated periodic syndromes (CAPS). J Inflamm Res. 2010;3:1–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  121. Hoffman HM. Rilonacept for the treatment of cryopyrin-associated periodic syndromes (CAPS). Expert Opin Biol Ther. 2009;9:519–31.

    Article  CAS  PubMed  Google Scholar 

  122. Ilowite NT, Prather K, Lokhnygina Y, et al. Randomized, double-blind, placebo-controlled trial of the efficacy and safety of rilonacept in the treatment of systemic juvenile idiopathic arthritis. Arthritis Rheumatol. 2014;66:2570–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Autmizguine J, Cohen-Wolkowiez M, Ilowite N, Investigators, R. Rilonacept pharmacokinetics in children with systemic juvenile idiopathic arthritis. J Clin Pharmacol. 2015;55:39–44.

    Article  CAS  PubMed  Google Scholar 

  124. Don BR, Spin G, Nestorov I, Hutmacher M, Rose A, Kaysen GA. The pharmacokinetics of etanercept in patients with end-stage renal disease on haemodialysis. J Pharm Pharmacol. 2005;57:1407–13.

    Article  CAS  PubMed  Google Scholar 

  125. Radin A, Marbury T, Osgood G, Belomestnov P. Safety and pharmacokinetics of subcutaneously administered rilonacept in patients with well-controlled end-stage renal disease (ESRD). J Clin Pharmacol. 2010;50:835–41.

    Article  CAS  PubMed  Google Scholar 

  126. Lovell DJ, Giannini EH, Reiff AO, et al. Long-term safety and efficacy of rilonacept in patients with systemic juvenile idiopathic arthritis. Arthritis Rheum. 2013;65:2486–96.

    Article  CAS  PubMed  Google Scholar 

  127. Schumacher HR Jr, Evans RR, Saag KG, et al. Rilonacept (interleukin-1 trap) for prevention of gout flares during initiation of uric acid-lowering therapy: results from a phase III randomized, double-blind, placebo-controlled, confirmatory efficacy study. Arthritis Care Res (Hoboken). 2012;64:1462–70.

    Article  CAS  Google Scholar 

  128. Mitha E, Schumacher HR, Fouche L, et al. Rilonacept for gout flare prevention during initiation of uric acid-lowering therapy: results from the PRESURGE-2 international, phase 3, randomized, placebo-controlled trial. Rheumatology. 2013;52:1285–92.

    Article  CAS  PubMed  Google Scholar 

  129. Sundy JS, Schumacher HR, Kivitz A, et al. Rilonacept for gout flare prevention in patients receiving uric acid-lowering therapy: results of RESURGE, a phase III, international safety study. J Rheumatol. 2014;41:1703–11.

    Article  CAS  PubMed  Google Scholar 

  130. Hoffman HM, Throne ML, Amar NJ, et al. Long-term efficacy and safety profile of rilonacept in the treatment of cryopryin-associated periodic syndromes: results of a 72-week open-label extension study. Clin Ther. 2012;34:2091–103.

    Article  CAS  PubMed  Google Scholar 

  131. Hashkes PJ, Spalding SJ, Giannini EH, et al. Rilonacept for colchicine-resistant or -intolerant familial Mediterranean fever: a randomized trial. Ann Intern Med. 2012;157:533–41.

    Article  PubMed  Google Scholar 

  132. Hoffman HM, Throne ML, Amar NJ, et al. Efficacy and safety of rilonacept (interleukin-1 trap) in patients with cryopyrin-associated periodic syndromes: results from two sequential placebo-controlled studies. Arthritis Rheum. 2008;58:2443–52.

    Article  CAS  PubMed  Google Scholar 

  133. Goldbach-Mansky R, Shroff SD, Wilson M, et al. A pilot study to evaluate the safety and efficacy of the long-acting interleukin-1 inhibitor rilonacept (interleukin-1 trap) in patients with familial cold autoinflammatory syndrome. Arthritis Rheum. 2008;58:2432–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Garg M, de Jesus AA, Chapelle D et al. Rilonacept maintains long-term inflammatory remission in patients with deficiency of the IL-1 receptor antagonist. JCI Insight. 2017;2.

    Google Scholar 

  135. Petryna O, Cush JJ, Efthimiou P. IL-1 trap rilonacept in refractory adult onset Still’s disease. Ann Rheum Dis. 2012;71:2056–7.

    Article  PubMed  Google Scholar 

  136. Terkeltaub R, Sundy JS, Schumacher HR, et al. The interleukin 1 inhibitor rilonacept in treatment of chronic gouty arthritis: results of a placebo-controlled, monosequence crossover, non-randomised, single-blind pilot study. Ann Rheum Dis. 2009;68:1613–7.

    Article  CAS  PubMed  Google Scholar 

  137. Schumacher HR Jr, Sundy JS, Terkeltaub R, et al. Rilonacept (interleukin-1 trap) in the prevention of acute gout flares during initiation of urate-lowering therapy: results of a phase II randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2012;64:876–84.

    Article  CAS  PubMed  Google Scholar 

  138. Krause K, Weller K, Stefaniak R, et al. Efficacy and safety of the interleukin-1 antagonist rilonacept in Schnitzler syndrome: an open-label study. Allergy. 2012;67:943–50.

    Article  CAS  PubMed  Google Scholar 

  139. Brik R, Butbul-Aviel Y, Lubin S, et al. Canakinumab for the treatment of children with colchicine-resistant familial Mediterranean fever: a 6-month open-label, single-arm pilot study. Arthritis Rheumatol (Hoboken, NJ). 2014;66:3241–3.

    Article  CAS  Google Scholar 

  140. Gul A, Ozdogan H, Erer B, et al. Efficacy and safety of canakinumab in adolescents and adults with colchicine-resistant familial Mediterranean fever. Arthritis Res Ther. 2015;17:243.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  141. De Benedetti F, Gattorno M, Anton J, et al. Canakinumab for the treatment of autoinflammatory recurrent fever syndromes. N Engl J Med. 2018;378:1908–19.

    Article  PubMed  Google Scholar 

  142. Arostegui JI, Anton J, Calvo I, et al. Open-label, Phase II Study to assess the efficacy and safety of canakinumab treatment in active hyperimmunoglobulinemia D with periodic fever syndrome. Arthritis Rheumatol (Hoboken, NJ). 2017;69:1679–88.

    Article  CAS  Google Scholar 

  143. Gattorno M, Obici L, Cattalini M, et al. Canakinumab treatment for patients with active recurrent or chronic TNF receptor-associated periodic syndrome (TRAPS): an open-label, phase II study. Ann Rheum Dis. 2017;76:173–8.

    Article  CAS  PubMed  Google Scholar 

  144. Caorsi R, Lepore L, Zulian F, et al. The schedule of administration of canakinumab in cryopyrin associated periodic syndrome is driven by the phenotype severity rather than the age. Arthritis Res Ther. 2013;15:R33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Kuemmerle-Deschner JB, Hachulla E, Cartwright R, et al. Two-year results from an open-label, multicentre, phase III study evaluating the safety and efficacy of canakinumab in patients with cryopyrin-associated periodic syndrome across different severity phenotypes. Ann Rheum Dis. 2011;70:2095–102.

    Article  CAS  PubMed  Google Scholar 

  146. Lachmann HJ, Kone-Paut I, Kuemmerle-Deschner JB, et al. Use of canakinumab in the cryopyrin-associated periodic syndrome. N Engl J Med. 2009;360:2416–25.

    Article  CAS  PubMed  Google Scholar 

  147. Ruperto N, Brunner HI, Quartier P, et al. Two randomized trials of canakinumab in systemic juvenile idiopathic arthritis. N Engl J Med. 2012;367:2396–406.

    Article  CAS  PubMed  Google Scholar 

  148. Ruperto N, Quartier P, Wulffraat N, et al. A phase II, multicenter, open-label study evaluating dosing and preliminary safety and efficacy of canakinumab in systemic juvenile idiopathic arthritis with active systemic features. Arthritis Rheum. 2012;64:557–67.

    Article  CAS  PubMed  Google Scholar 

  149. Feist E, Quartier P, Fautrel B, et al. Efficacy and safety of canakinumab in patients with Stills disease: exposure-response analysis of pooled systemic juvenile idiopathic arthritis data by age groups. Clin Exp Rheumatol. 2018;36(4):668–75.

    PubMed  Google Scholar 

  150. Junge G, Mason J, Feist E. Adult onset Still’s disease—the evidence that anti-interleukin-1 treatment is effective and well-tolerated (a comprehensive literature review). Semin Arthritis Rheum. 2017;47:295–302.

    Article  CAS  PubMed  Google Scholar 

  151. Simonini G, Xu Z, Caputo R, et al. Clinical and transcriptional response to the long-acting interleukin-1 blocker canakinumab in Blau syndrome-related uveitis. Arthritis Rheum. 2013;65:513–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Kolios AG, Maul JT, Meier B, et al. Canakinumab in adults with steroid-refractory pyoderma gangrenosum. Br J Dermatol. 2015;173:1216–23.

    Article  CAS  PubMed  Google Scholar 

  153. Moussa T, Bhat V, Kini V, Fathalla BM. Clinical and genetic association, radiological findings and response to biological therapy in seven children from Qatar with non-bacterial osteomyelitis. Int J Rheum Dis. 2017;20:1286–96.

    Article  CAS  PubMed  Google Scholar 

  154. Lopalco G, Rigante D, Vitale A, Caso F, Iannone F. Canakinumab efficacy in refractory adult-onset PFAPA syndrome. Int J Rheum Dis. 2017;20:1050–1.

    Article  PubMed  Google Scholar 

  155. Schlesinger N, Alten RE, Bardin T, et al. Canakinumab for acute gouty arthritis in patients with limited treatment options: results from two randomised, multicentre, active-controlled, double-blind trials and their initial extensions. Ann Rheum Dis. 2012;71:1839–48.

    Article  CAS  PubMed  Google Scholar 

  156. Schlesinger N, Mysler E, Lin HY, et al. Canakinumab reduces the risk of acute gouty arthritis flares during initiation of allopurinol treatment: results of a double-blind, randomised study. Ann Rheum Dis. 2011;70:1264–71.

    Article  CAS  PubMed  Google Scholar 

  157. 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;62:3064–76.

    Article  CAS  PubMed  Google Scholar 

  158. Orlando I, Vitale A, Rigante D, Lopalco G, Fabiani C, Cantarini L. Long-term efficacy and safety of the interleukin-1 inhibitors anakinra and canakinumab in refractory Behcet disease uveitis and concomitant bladder papillary carcinoma. Intern Med J. 2017;47:1086–8.

    Article  CAS  PubMed  Google Scholar 

  159. Ugurlu S, Ucar D, Seyahi E, Hatemi G, Yurdakul S. Canakinumab in a patient with juvenile Behcet’s syndrome with refractory eye disease. Ann Rheum Dis. 2012;71:1589–91.

    Article  PubMed  Google Scholar 

  160. Vitale A, Rigante D, Caso F, et al. Inhibition of interleukin-1 by canakinumab as a successful mono-drug strategy for the treatment of refractory Behcet’s disease: a case series. Dermatology (Basel, Switzerland). 2014;228:211–4.

    Article  Google Scholar 

  161. de Koning HD, Schalkwijk J, van der Ven-Jongekrijg J, Stoffels M, van der Meer JW, Simon A. Sustained efficacy of the monoclonal anti-interleukin-1 beta antibody canakinumab in a 9-month trial in Schnitzler’s syndrome. Ann Rheum Dis. 2013;72:1634–8.

    Article  PubMed  CAS  Google Scholar 

  162. Krause K, Tsianakas A, Wagner N, et al. Efficacy and safety of canakinumab in Schnitzler syndrome: a multicenter randomized placebo-controlled study. J Allergy Clin Immunol. 2017;139:1311–20.

    Article  CAS  PubMed  Google Scholar 

  163. Ridker PM, Everett BM, Thuren T, et al. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med. 2017;377:1119–31.

    Article  CAS  PubMed  Google Scholar 

  164. Ridker PM, Howard CP, Walter V, et al. Effects of interleukin-1beta inhibition with canakinumab on hemoglobin A1c, lipids, C-reactive protein, interleukin-6, and fibrinogen: a phase IIb randomized, placebo-controlled trial. Circulation. 2012;126:2739–48.

    Article  CAS  PubMed  Google Scholar 

  165. Rissanen A, Howard CP, Botha J, Thuren T. Effect of anti-IL-1beta antibody (canakinumab) on insulin secretion rates in impaired glucose tolerance or type 2 diabetes: results of a randomized, placebo-controlled trial. Diabetes Obes Metab. 2012;14:1088–96.

    Article  CAS  PubMed  Google Scholar 

  166. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Chakraborty A, Tannenbaum S, Rordorf C, et al. Pharmacokinetic and pharmacodynamic properties of canakinumab, a human anti-interleukin-1beta monoclonal antibody. Clin Pharmacokinet. 2012;51:e1–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  168. Chakraborty A, Van LM, Skerjanec A, et al. Pharmacokinetic and pharmacodynamic properties of canakinumab in patients with gouty arthritis. J Clin Pharmacol. 2013;53:1240–51.

    Article  CAS  PubMed  Google Scholar 

  169. Noe A, Howard C, Thuren T, Taylor A, Skerjanec A. Pharmacokinetic and pharmacodynamic characteristics of single-dose canakinumab in patients with type 2 diabetes mellitus. Clin Ther. 2014;36:1625–37.

    Article  CAS  PubMed  Google Scholar 

  170. Sun H, Van LM, Floch D, et al. Pharmacokinetics and pharmacodynamics of canakinumab in patients with systemic juvenile idiopathic arthritis. J Clin Pharmacol. 2016;56:1516–27.

    Article  CAS  PubMed  Google Scholar 

  171. Sibley CH, Chioato A, Felix S, et al. A 24-month open-label study of canakinumab in neonatal-onset multisystem inflammatory disease. Ann Rheum Dis. 2015;74:1714–9.

    Article  CAS  PubMed  Google Scholar 

  172. Rodriguez-Smith J, Lin YC, Tsai WL, et al. Cerebrospinal fluid cytokines correlate with aseptic meningitis and blood-brain barrier function in neonatal-onset multisystem inflammatory disease: central nervous system biomarkers in neonatal-onset multisystem inflammatory disease correlate with central nervous system inflammation. Arthritis Rheumatol (Hoboken, NJ). 2017;69:1325–36.

    Article  CAS  Google Scholar 

  173. Brogan PHM, Kuemmerle-Deschner J. FRI0503 efficacy and safety of canakinumab in patients with cryopyrin associated periodic syndromes: an open-label, phase-III, extension study. Ann Rheum Dis. 2016;75(suppl 2):620–1.

    Article  Google Scholar 

  174. Ridker PM, MacFadyen JG, Thuren T, et al. Effect of interleukin-1beta inhibition with canakinumab on incident lung cancer in patients with atherosclerosis: exploratory results from a randomised, double-blind, placebo-controlled trial. Lancet. 2017;390:1833–42.

    Article  CAS  PubMed  Google Scholar 

  175. Chioato A, Noseda E, Felix SD, et al. Influenza and meningococcal vaccinations are effective in healthy subjects treated with the interleukin-1 beta-blocking antibody canakinumab: results of an open-label, parallel group, randomized, single-center study. Clin Vaccine Immunol. 2010;17:1952–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  176. Jaeger VK, Hoffman HM, van der Poll T, et al. Safety of vaccinations in patients with cryopyrin-associated periodic syndromes: a prospective registry based study. Rheumatology. 2017;56:1484–91.

    Article  CAS  PubMed  Google Scholar 

  177. Walker UA, Hoffman HM, Williams R, Kuemmerle-Deschner J, Hawkins PN. Brief report: severe inflammation following vaccination against streptococcus pneumoniae in patients with cryopyrin-associated periodic syndromes. Arthritis Rheumatol. 2016;68:516–20.

    Article  CAS  PubMed  Google Scholar 

  178. Kang I. Editorial: is the NLPR3 Inflammasome “overheated” by pneumococcal vaccination in cryopyrin-associated periodic syndromes? Arthritis Rheumatol. 2016;68:274–6.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Pediatric Pulmonology, Immunology and Intensive Care Medicine, Charité University Medicine Berlin, Berlin, Germany

    Tilmann Kallinich

  2. Division of Rheumatology and Laboratory of Immuno Rheumatology, Ospedale Pediatrico Bambino Gesù, Rome, Italy

    Fabrizio de Benedetti

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Correspondence to Fabrizio de Benedetti .

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  1. Pediatric Rheumatology Unit, Shaare Zedek Medical Center and Hebrew University, Jerusalem, Israel

    Philip J. Hashkes

  2. Department Paediatrics, Division of Rheumatology, The Hospital for Sick Children and University of Toronto, Toronto, ON, Canada

    Ronald M. Laxer

  3. Department of Internal Medicine, Radboudumc Expertisecenter for Immunodeficiency and Autoinflammation, Radboud University Medical Center, Nijmegen, The Netherlands

    Anna Simon

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Kallinich, T., de Benedetti, F. (2019). Interleukin (IL)-1 Blocking Compounds and Their Use in Autoinflammatory Diseases. In: Hashkes, P., Laxer, R., Simon, A. (eds) Textbook of Autoinflammation. Springer, Cham. https://doi.org/10.1007/978-3-319-98605-0_41

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