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Extended report
A 24-month open-label study of canakinumab in neonatal-onset multisystem inflammatory disease
  1. Cailin H Sibley1,
  2. Andrea Chioato2,
  3. Sandra Felix2,
  4. Laurence Colin2,
  5. Abhijit Chakraborty2,
  6. Nikki Plass1,
  7. Jackeline Rodriguez-Smith1,
  8. Carmen Brewer3,
  9. Kelly King3,
  10. Christopher Zalewski3,
  11. H Jeffrey Kim3,
  12. Rachel Bishop4,
  13. Ken Abrams2,
  14. Deborah Stone1,
  15. Dawn Chapelle1,
  16. Bahar Kost1,
  17. Christopher Snyder1,
  18. John A Butman5,
  19. Robert Wesley6,
  20. Raphaela Goldbach-Mansky1
  1. 1Translational Autoinflammatory Disease Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases at the National Institutes of Health, Bethesda, Maryland, USA
  2. 2Novartis Institutes for BioMedical Research, Basel, Switzerland
  3. 3Otolaryngology Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland, USA
  4. 4National Eye Institute, National Institutes of Health, Bethesda, Maryland, USA
  5. 5Diagnostic Radiology Department, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA
  6. 6Clinical Center, National Institutes of Health, Bethesda, Maryland, USA
  1. Correspondence to Dr Raphaela Goldbach-Mansky, Translational Autoinflammatory Section, NIH/NIAMS, Building 10 Room 6D47-B, 10 Center Dr., Bethesda, MD 20892, USA; goldbacr{at}


Objective To study efficacy and safety of escalating doses of canakinumab, a fully human anti-IL-1β monoclonal antibody in the severe cryopyrin-associated periodic syndrome, neonatal-onset multisystem inflammatory disease (NOMID).

Methods 6 patients were enrolled in this 24-month, open-label phase I/II study. All underwent anakinra withdrawal. The initial subcutaneous canakinumab dose was 150 mg (or 2 mg/kg in patients ≤40 kg) or 300 mg (or 4 mg/kg) with escalation up to 600 mg (or 8 mg/kg) every 4 weeks. Full remission was remission of patient-reported clinical components and measures of systemic inflammation and CNS inflammation. Hearing, vision and safety were assessed. Primary endpoint was full remission at month 6.

Results All patients flared after anakinra withdrawal, and symptoms and serum inflammatory markers improved with canakinumab. All patients required dose escalation to the maximum dose. At month 6, none had full remission, although 4/6 achieved inflammatory remission, based on disease activity diary scores and normal C-reactive proteins. None had CNS remission; 5/6 due to persistent CNS leucocytosis. At the last study visit, 5/6 patients achieved inflammatory remission and 4/6 had continued CNS leucocytosis. Visual acuity and field were stable in all patients, progressive hearing loss occurred in 1/10 ears. Adverse events (AEs) were rare. One serious AE (abscess due to a methicillin-resistant Staphylococcus aureus infection) occurred.

Conclusions Canakinumab at the studied doses improves symptoms and serum inflammatory features of NOMID, although low-grade CNS leukocytosis in four patients and headaches in one additional patient persisted. Whether further dose intensifications are beneficial in these cases remains to be assessed. identifier NCT00770601.

  • Cytokines
  • DMARDs (Biologic)
  • Disease Activity
  • Inflammation

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