This is Cryopyrin-
Associated Periodic
Syndromes (CAPS)

CAPS is a rare, hereditary autoinflammatory disorder caused by mutations in the NLRP3 gene which codes for the protein cryopyrin1

CAPS-associated mutations increase NLRP3 inflammasome activation and production of the proinflammatory cytokine IL-1β, which plays a pivotal role in local and systemic inflammation in CAPS.1

The prevalence of CAPS is 2.7-5.5/million people worldwide, however it may be underestimated as CAPS is not widely known and may be misdiagnosed.2 CAPS includes three main clinical phenotypes: Familial Cold Autoinflammatory Syndrome (FCAS), Muckle-Wells Syndrome (MWS), and Neonatal-Onset Multisystem Inflammatory Disease (NOMID), also known as Chronic Infantile Neurological Cutaneous and Articular Syndrome (CINCA). CAPS is characterized by systemic inflammation, leading to symptoms such as fever, rash, joint pain, and fatigue. If left uncontrolled, it can result in irreversible organ damage, including hearing loss, AA amyloidosis*, vision loss, skeletal deformities, and cognitive disability.3

The symptoms of CAPS range in severity and are often present in childhood, but diagnosis may be delayed due to its rarity and lack of disease awareness. Early diagnosis and treatment initiation are critical to delay and/or prevent irreversible organ damage in patients with the more severe forms of CAPS.1-4

common symptoms

Typical signs and symptoms associated with CAPS3

Treatment of CAPS

The goal of treatment in CAPS is to suppress systemic inflammation, prevent organ damage and improve the patient’s quality of life.1-4

EULAR/ACR currently recommend three IL-1 inhibitors, including Kineret, as the standard of care for CAPS. Dosing should be adjusted according to the severity and activity of the disease in a treat-to-target approach to resolve clinical symptoms and normalize inflammatory markers, and adjusted for weight gain and appropriate development in the growing patient. Regular monitoring by a multidisciplinary team to help manage any organ manifestations is recommended.3

efficacy in cryopyrin-associated periodic syndromes (caps)

A valuable asset for the treatment of CAPS

Clinical studies in CAPS have shown that Kineret provides rapid and sustained resolution of CAPS symptoms and reduction of inflammatory biomarkers.5 In the severe forms of CAPS, long-term treatment with Kineret has been shown to improve the systemic inflammatory organ manifestations of the eye, inner ear, and CNS.8

Kineret provide rapid and sustained resolution of CAPS symptoms5-8

In a pivotal study assessing the efficacy of Kineret in both children and adults with NOMID, the most severe form of CAPS, patients who were treated with anakinra (up to 5 mg/kg/day) experienced a significant and rapid reduction in frequently occurring symptoms such as fever, rash, joint pain, headache, fatigue, and conjunctivitis.6-7

Blocking IL-1 led to improvement and stabilization of inflammatory biomarkers such as SAA, CRP, and ESR.6-7

During Kineret treatment:

  • Mean corticosteroid usage was reduced7
  • Global diary score decreased significantly6
  • CHAQ-score decreased significantly6
  • Hearing loss and vision impairment were halted or improved with Kineret treatment across the age ranges6
  • No further bony lesions were seen after initiating Kineret7
  • Markers of CNS inflammation were reduced significantly at 36 months7

Global Diary Score= Median daily scores of five symptoms (fever, rash, headache, joint pain, and vomiting) were evaluated daily with the use of a scale that ranged from 0 (no symptoms) to 4 (severe symptoms) (possible total range, 0 to 20). The maximal daily score measured was 14; the minimal score was 0.

* AA Amyloidosis can occur as a response to a chronic inflammatory disease or infection. These conditions cause the liver to produce high levels of a protein called serum amyloid A (SAA), which may form abnormal fibril protein aggregates in tissues and organs, leading to AA amyloidosis.

Abbreviations

CHAQ, Childhood Health Assessment Questionnaire (CHAQ), a standardized test for the assessment of disability, range from 0 to 3, with higher scores indicating more severe impairment; NLRP3, NOD-like receptor family pyrin domain-containing 3; CRP, C-reactive protein; SAA, serum amyloid A; ESR, erythrocyte sedimentation rate; IL-1, Interleukin-1; CNS, central nervous system

Kineret Q&A

How is Kineret administered?
  • Kineret is given in a pre-filled syringe containing 100 mg of anakinra per 0.67 ml (150 mg/ml).1
  • Kineret is given as a subcutaneous injection.1
  • Dosage depends on indication. In children, the dose is determined depending on body weight. Please refer to current SmPC.
How should Kineret be stored?
  • Kineret should be stored in a refrigerator between 2°C and 8°C.1
  • Kineret should not be frozen or shaken.1
  • Kineret should be kept in its original carton and away from light.1

References

  • Kuemmerle-Deschner JB, Ozen S, Tyrrell PN, Kone-Paut I, Goldbach-Mansky R, Lachmann H, Blank N, Hoffman HM, Weissbarth- Riedel E, Hugle B, Kallinich T, Gattorno M, Gul A, Ter Haar N, Oswald M, Dedeoglu F, Cantarini L, Benseler SM. Diagnostic criteria for cryopyrin-associated periodic syndrome (CAPS). Ann Rheum Dis. 2017 Jun;76(6):942-947. doi: 10.1136/ annrheumdis-2016-209686. Epub 2016 Oct 4. PMID: 27707729.
  • Welzel T, Kuemmerle-Deschner JB. Diagnosis and Management of the Cryopyrin-Associated Periodic Syndromes (CAPS): What Do We Know Today? J Clin Med. 2021 Jan 1;10(1):128. doi: 10.3390/jcm10010128. PMID: 33401496; PMCID: PMC7794776.
  • Romano M, Arici ZS, Piskin D, Alehashemi S, Aletaha D, Barron KS, Benseler S, Berard R, Broderick L, Dedeoglu F, Diebold M, Durrant KL, Ferguson P, Foell D, Hausmann J, Jones OY, Kastner DL, Lachmann HJ, Laxer RM, Rivera D, Ruperto N, Simon A, Twilt M, Frenkel J, Hoffman H, de Jesus AA, Kuemmerle-Deschner JB, Ozen S, Gattorno M, Goldbach-Mansky R, Demirkaya E. The 2021 EULAR/American College of Rheumatology points to consider for diagnosis, management and monitoring of the interleukin-1 mediated autoinflammatory diseases: cryopyrin-associated periodic syndromes, tumour necrosis factor receptor-associated periodic syndrome, mevalonate kinase deficiency, and deficiency of the interleukin-1 receptor antagonist. Ann Rheum Dis. 2022 Jul;81(7):907-921. doi: 10.1136/annrheumdis-2021-221801. Epub 2022 May 27. PMID: 35623638.
  • Hansmann S, Lainka E, Horneff G, Holzinger D, Rieber N, Jansson AF, Rösen-Wolff A, Erbis G, Prelog M, Brunner J, Benseler SM, Kuemmerle-Deschner JB. Consensus protocols for the diagnosis and management of the hereditary autoinflammatory syndromes CAPS, TRAPS and MKD/HIDS: a German PRO-KIND initiative. Pediatr Rheumatol Online J. 2020 Feb 17;18(1):17. doi: 10.1186/ s12969-020-0409-3. PMID: 32066461; PMCID: PMC7027082.
  • Swedish Orphan Biovitrum AB (publ). Kineret summary of product characteristics [SmPC]. Latest version available from: https:// www.ema.europa.eu/en/documents/product-information/kineret-epar-product-information_en.pdf
  • Goldbach-Mansky R, Dailey NJ, Canna SW, Gelabert A, Jones J, Rubin BI, Kim HJ, Brewer C, Zalewski C, Wiggs E, Hill S, Turner ML, Karp BI, Aksentijevich I, Pucino F, Penzak SR, Haverkamp MH, Stein L, Adams BS, Moore TL, Fuhlbrigge RC, Shaham B, Jarvis JN, O'Neil K, Vehe RK, Beitz LO, Gardner G, Hannan WP, Warren RW, Horn W, Cole JL, Paul SM, Hawkins PN, Pham TH, Snyder C, Wesley RA, Hoffmann SC, Holland SM, Butman JA, Kastner DL. Neonatal-onset multisystem inflammatory disease responsive to interleukin-1beta inhibition. N Engl J Med. 2006 Aug 10;355(6):581-92. doi: 10.1056/NEJMoa055137. PMID: 16899778; PMCID: PMC4178954.
  • Sibley CH, Plass N, Snow J, Wiggs EA, Brewer CC, King KA, Zalewski C, Kim HJ, Bishop R, Hill S, Paul SM, Kicker P, Phillips Z, Dolan JG, Widemann B, Jayaprakash N, Pucino F, Stone DL, Chapelle D, Snyder C, Butman JA, Wesley R, Goldbach-Mansky R. Sustained response and prevention of damage progression in patients with neonatal-onset multisystem inflammatory disease treated with anakinra: a cohort study to determine three- and five-year outcomes. Arthritis Rheum. 2012 Jul;64(7):2375-86. doi: 10.1002/ art.34409. PMID: 22294344; PMCID: PMC3474541.
  • Kullenberg T, Löfqvist M, Leinonen M, Goldbach-Mansky R, Olivecrona H. Long-term safety profile of anakinra in patients with severe cryopyrin-associated periodic syndromes. Rheumatology (Oxford). 2016 Aug;55(8):1499-506. doi: 10.1093/rheumatology/ kew208. Epub 2016 May 3. PMID: 27143789; PMCID: PMC4957676.