The Role of IL-1

How IL-1 fits into autoinflammation

Interleukin-1 alpha (IL-1α) and interleukin-1 beta (IL-1β) are proinflammatory cytokines that play a key role in autoinflammation. IL-1 cytokines are primarily associated with innate immunity, typically as a mechanism of defense.1 When uncontrolled, IL-1 activity can lead to damaging systemic inflammation and the symptoms of autoinflammatory diseases.2-4 The impact of IL-1 is not limited to autoinflammation, but also influences the adaptive immune system, causing persistent inflammation in autoimmune diseases as well.5,6

Uncontrolled IL-1 activity can lead to chronic and sometimes life-threatening systemic inflammation3,5

A chart showing various functions of IL-1 and how it can play a role in various types of systemic inflammation or damage
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When the IL-1 pathway is dysregulated, it creates a destructive immune response that adversely impacts a wide variety of tissues and organs.3,10

IL-1–mediated autoinflammation can have direct and indirect involvement in multiple diseases6

  • IL-1 dysregulation is a primary driver of autoinflammatory disorders such as cryopyrin-associated periodic syndromes (CAPS) and deficiency of interleukin-1 receptor antagonist (DIRA)2,3,6
  • IL-1–mediated autoinflammation can also be a component of diseases like rheumatoid arthritis (RA), typically considered to be autoimmune in nature7

Whether it is driven by the innate or adaptive immune system, extraarticular manifestations of autoinflammation can include:

  • Recurrent fever7,11,12
  • Painful skin rashes7,13
  • Headaches13
  • Fatigue7,11,12
  • Muscle weakness12
  • Keratoconjunctivitis sicca (dry eye)12
  • Hypotension7
  • Elevated acute-phase reactants (C-reactive protein [CRP], erythrocyte sedimentation rate [ESR])7,12
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IL-1–mediated autoinflammation can lead to long-term, irreversible damage and disability14

Learn about how IL-1 impacts
RA patients.

For RA patients

Learn about how IL-1 impacts
NOMID patients.

For NOMID patients

Learn about how IL-1 impacts
DIRA patients.

For DIRA patients
Important Safety Information
INDICATION

KINERET® (anakinra) is an interleukin-1 receptor antagonist indicated for:

Rheumatoid Arthritis (RA). Reduction in signs and symptoms and slowing the progression of structural damage in moderately to severely active rheumatoid arthritis, in patients 18 years of age or older who have failed 1 or more disease-modifying antirheumatic drugs (DMARDs)

Cryopyrin-Associated Periodic Syndromes (CAPS). Treatment of Neonatal-Onset Multisystem Inflammatory Disease (NOMID)

Deficiency of Interleukin-1 Receptor Antagonist (DIRA). Treatment of Deficiency of Interleukin-1 Receptor Antagonist (DIRA)

CONTRAINDICATION

KINERET is contraindicated in patients with known hypersensitivity to E. coli–derived proteins, KINERET, or to any components of the product

IMPORTANT SAFETY INFORMATION

Serious Infections. In RA, discontinue use if serious infection develops. In KINERET-treated NOMID or DIRA patients, the risk of a disease flare when discontinuing KINERET treatment should be weighed against the potential risk of continued treatment. Do not initiate KINERET in patients with active infections

Use in combination with Tumor Necrosis Factor (TNF)-blocking agents is not recommended

Hypersensitivity reactions, including anaphylactic reactions and angioedema, and serious cutaneous reactions including drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported. Patients with DIRA may have an increased risk of allergic reactions, particularly in the first several weeks after starting KINERET treatment

Immunosuppression. The impact of treatment with KINERET on active and/or chronic infections and the development of malignancies is not known

Immunizations. Live vaccines should not be given concurrently with KINERET

Neutrophil counts should be assessed prior to initiating KINERET treatment, and while receiving KINERET, monthly for 3 months, and thereafter quarterly for a period up to 1 year

Serious Adverse Reactions

RA: The most serious adverse reactions were: Serious Infections and Neutropenia, particularly when used in combination with TNF blocking agents.

NOMID and DIRA: The most serious adverse events were infections.

Most Common Adverse Reactions

RA: The most common adverse reactions (incidence ≥ 5%) are injection site reaction, worsening of rheumatoid arthritis, upper respiratory tract infection, headache, nausea, diarrhea, sinusitis, arthralgia, flu-like symptoms, and abdominal pain

NOMID: The most common AEs during the first 6 months of treatment (incidence > 10%) are injection site reaction, headache, vomiting, arthralgia, pyrexia, and nasopharyngitis

DIRA: The most common AEs are upper respiratory tract infections, rash, pyrexia, influenza-like illness, and gastroenteritis

Post-marketing Experience

Hepato-biliary disorders (elevations of transaminases; non-infectious hepatitis) and thrombocytopenia, including severe thrombocytopenia and DRESS have been identified during postapproval use of KINERET. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

These are not all the possible risks associated with KINERET. Please see Full Prescribing Information for KINERET at https://www.KineretRxHCP.com/home.php
To report suspected adverse reactions, contact Sobi North America at 1-866-773-5274 or FDA at 1-800-FDA-1088
Click here for full Prescribing Information for KINERET.
For more information about WAC pricing, click here.

References: 1. Dinarello CA. Overview of the IL-1 family in innate inflammation and acquired immunity. Immunol Rev. 2018;281(1):8-27. 2. KINERET [Prescribing Information]. Stockholm, Sweden: Swedish Orphan Biovitrum AB (publ). 3. Diaz A. Deficiency of the interleukin-1 receptor antagonist (DIRA). In: Efthimiou P (ed). Auto-Inflammatory Syndromes. Springer, Cham; 2019:69-83. 4. Goldbach-Mansky R, Dailey NJ, Canna SW, et al. Neonatal-onset multisystem inflammatory disease responsive to interleukin-1β inhibition. N Engl J Med. 2006;355(6):581-592. 5. Buch MH, Eyre S, McGonagle D. Persistent inflammatory and non-inflammatory mechanisms in refractory rheumatoid arthritis. Nat Rev Rheumatol. 2021;17(1):17-33. 6. Lopalco G, Cantarini L, Vitale A, et al. Interleukin-1 as a common denominator from autoinflammatory to autoimmune disorders: premises, perils, and perspectives. Mediators Inflamm. 2015;2015:194864. 7. Dinarello CA, Simon A, van der Meer JWM. Treating inflammation by blocking interleukin-1 in a broad spectrum of diseases. Nat Rev Drug Discov. 2012;11(8):633-652. 8. Arend WP, Dayer J-M. Cytokines and cytokine inhibitors or antagonists in rheumatoid arthritis. Arthritis Rheum. 1990;33(3):305-315. 9. van den Berg WB. Arguments for interleukin 1 as a target in chronic arthritis. Ann Rheum Dis. 2000;59(suppl 1):i81-i84. 10. Kay J, Calabrese L. The role of interleukin-1 in the pathogenesis of rheumatoid arthritis. Rheumatology (Oxford). 2004;43(suppl 3):iii2-iii9. 11. Dinarello CA. Interleukin-1 in the pathogenesis and treatment of inflammatory diseases. Blood. 2011;117(14):3720-3732. 12. Vela P. Extra-articular manifestations of rheumatoid arthritis, now. Eur Med J Rheumatol. 2014;1:103-112. 13. Hashkes PJ, Toker O. Autoinflammatory syndromes. Pediatr Clin North Am. 2012;59(2):447-470. 14. Goldbach-Mansky R. Current status of understanding the pathogenesis and management of patients with NOMID/CINCA. Curr Rheumatol Rep. 2011;13(2):123-131.