Prescribing information

 

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ILARIS is the first selective IL-1β inhibitor for the treatment of FMF, HIDS/MKD, TRAPS, CAPS and Still’s disease (AOSD and SJIA) in adults, adolescents and children aged ≥2 years.1–3

 

 

ILARIS mechanism of action

 

Image of target with a green centre.

In autoinflammatory diseases such as SJIA, dysregulation of the innate immune system results in aberrant activation of phagocytes, consequently leading to overproduction of key inflammatory cytokines, such as IL-1β.17

ILARIS is a fully human monoclonal antibody that binds with high affinity to the proinflammatory cytokine IL-1β, blocking its interaction with IL-1 receptors, thereby neutralising its activity.1

 

Image showing the mechanism of action of ILARIS in periodic fever syndromes

Image created using information from references 1,4 and 17

ILARIS works to prevent IL-1β-induced gene activation and the production of inflammatory mediators1

 

Study designs

CLUSTER: A randomised, double-blind, placebo-controlled study to evaluate the efficacy and safety of ILARIS in patients with crFMF (n=63), HIDS/MKD (n=72) and TRAPS (n=46). Patients were randomised to receive 150 mg of ILARIS SC or placebo every 4 weeks. The primary outcome was complete response (resolution of their flare and no flare until Week 16). In the subsequent phase up to Week 40, patients who had complete response underwent a second randomisation to receive ILARIS every 8 weeks. The secondary outcomes were the proportion of patients who had PGA score of less than 2, a CRP level of 10 mg less per litre, or an SAA level of 10 mg or less per litre at Week 16.10,13

Lachmann HJ, et al. 2009: A three-part, randomised, 48-week, double blind, placebo-controlled withdrawal study of ILARIS in patients with CAPS (N=35). The primary outcome measure was the proportion of patients with a relapse of CAPS during canakinumab treatment, as compared with placebo, in part 2. Secondary outcome measures included the proportion of patients with a complete response in part 1, values of inflammatory markers, global assessments by physicians and patients, and safety and tolerability.11

Ruperto N, et al. 2012: Two parallel studies investigating the efficacy and safety of ILARIS in patients with SJIA. In trial 1, patients (aged 2 to 19 years) with SJIA and active systemic features (fever; ≥2 active joints; C-reactive protein, >30 mg per litre; and glucocorticoid dose, ≤1.0 mg per kilogram of body weight per day), were randomly assigned to receive ILARIS or placebo. The primary outcome, termed adapted JIA ACR 30 response, was defined as improvement of 30% or more in at least three of the six core criteria for JIA, worsening of more than 30% in no more than one of the criteria, and resolution of fever. In trial 2, after 32 weeks of open-label treatment with ILARIS, patients who had a response and underwent glucocorticoid tapering were randomly assigned to continued treatment with ILARIS or to placebo. The primary outcome was time to flare of systemic JIA.6
 

Indications1

Periodic fever syndromes
ILARIS is indicated for the treatment of the following autoinflammatory periodic fever syndromes in adults, adolescents and children aged 2 years and older:

  • CAPS, including:
    • Muckle-Wells syndrome (MWS)
    • Neonatal-onset multisystem inflammatory disease (NOMID)/chronic infantile neurological, cutaneous, articular syndrome (CINCA)
    • Severe forms of familial cold autoinflammatory syndrome (FCAS)/familial cold urticaria (FCU) presenting with signs and symptoms beyond cold-induced urticarial skin rash
  • TRAPS
  • HIDS/MKD
  • FMF
    • ILARIS should be given in combination with colchicine, if appropriate.

Still’s disease
ILARIS is also indicated in patients who have responded inadequately to previous therapy with non-steroidal anti-inflammatory drugs (NSAIDs) and systemic corticosteroids, for the treatment of:

  • Still’s disease, including:
    • Adult-onset Still’s disease (AOSD) 
    • Systemic juvenile idiopathic arthritis (SJIA) in patients aged 2 years and older 
    • ILARIS can be given as monotherapy or in combination with methotrexate 

ACR, albumin to creatinine ratio; AOSD, adult-onset Still’s disease; CAPS, cryopyrin-associated periodic syndromes; crFMF, colchicine-resistant familial Mediterranean fever; CRP, c-reactive protein; FCAS, familial cold autoinflammatory syndrome; FCU, familial cold urticaria; FMF, familial Mediterranean fever; HIDS, hyperimmunoglobulin D syndrome; IL, interleukin; JIA, juvenile idiopathic arthritis; MAS, macrophage activation syndrome; MKD, mevalonate kinase deficiency; PCS, SF-12 mental component summary score; PFS, SF-12 physical component summary score; PGA, physician global assessment; PhS, CHQ-PF50 physical component score; PsS, CHQ-PF5 psychosocial component summary score; SAA, serum amyloid A; SC, subcutaneous; SJIA, systemic juvenile idiopathic arthritis; TRAPS, tumour necrosis factor receptor-associated periodic syndrome.

References     

  1. ILARIS® (canakinumab) Summary of Product Characteristics.
  2. NHS England. Clinical Commissioning Policy: Canakinumab for treating periodic fever syndromes: TRAPS, HIDS/MKD and FMF (ages 2 years and older). February 2020. Available at: https://www.england.nhs.uk/wp-content/uploads/2020/03/Canakinumab-for-tr... [Accessed May 2023].
  3. NHS. Canakinumab engagement report. Available at: https://www.england.nhs.uk/wp-content/uploads/2022/10/2002-canakinumab-e... [Accessed May 2023].
  4. Lachmann HJ, et al. Arthritis Rheum 2011;63(2):314–324.
  5. Ruperto N, et al. Ann Rheum Dis 2016;75:265–266.
  6. Ruperto N, et al. N Engl J Med 2012;367(25):2396–2406.
  7. Özen S, et al. Ann Rheum Dis 2020;79:1362–1369.
  8. Migita K, et al. Immunologic Med 2018;41(2):55–61.
  9. Karabulut Y, et al. Rheumatol Int 2022;42(1):81–86.
  10. De Benedetti F, et al. N Engl J Med 2018;378(20):1908–1919.
  11. Lachmann HJ, et al. N Engl J Med 2009;360(23):2416–2425.
  12. Kuemmerle-Deschner J, et al. Pediatr Rheumatol 2015;13(Suppl 1):P3.
  13. Lachmann HJ, et al. Clin Exp Rheumatol 2021;39(Suppl 132[5]):51–58.
  14. Tomaras S, et al. J Clin Med 2021;10(4):733.
  15. Galozzi P, et al. Biologics 2021;16:21–34.
  16. Efthimiou P, et al. Semin Arthritis Rheum 2021;51(4):858–874.
  17. Lin YT et al. Autoimmun Rev 2011;10(8):482–489.
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UK | May 2023 | 261181

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