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

  • Tilmann Kallinich
  • Fabrizio de BenedettiEmail author
Chapter

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.

Keywords

Interleukin (IL-1) IL-1 receptor antagonist Anakinra Rilonacept Canakinumab 

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

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Pediatric Pulmonology, Immunology and Intensive Care MedicineCharité University Medicine BerlinBerlinGermany
  2. 2.Division of Rheumatology and Laboratory of Immuno RheumatologyOspedale Pediatrico Bambino GesùRomeItaly

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