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.

Abstract

Objective: Anakinra is approved for the treatment of RA and cryopyrin-associated periodic syndromes (CAPS). While the anakinra safety profile is well established in RA, the long-term safety profile in severe CAPS is less well documented and will therefore be discussed in this report.

Methods: A prospective, open-label, single centre, clinical cohort study was conducted at the National Institutes of Health in the USA, from 2003 to 2010, investigating the efficacy and safety of anakinra treatment for up to 5 years in 43 patients with CAPS. Safety was evaluated using adverse event (AE) reports, laboratory assessments, vital signs and diary reports.

Results: In total, 1233 AEs were reported during the study, with a yearly rate of 7.7 AEs per patient. The event rate decreased over time, and dose escalation during the study did not affect AE frequency. Anakinra had similar safety profiles in adults and children. The most frequently reported AEs were typical CAPS disease symptoms such as headache and arthralgia. Injection site reactions occurred mainly during the first month of anakinra treatment. In total, 14 patients experienced 24 serious AEs (SAEs), all of which resolved during the study period. The most common types of SAEs were infections such as pneumonia and gastroenteritis. There were no permanent discontinuations of treatment due to AEs.

Conclusion: In this study anakinra treatment of patients with severe CAPS for up to 5 years was safe and well tolerated both in paediatric and adult patients, with most AEs emerging during the first months after treatment initiation.

Trial registration: ClincialTrials.gov, clinicaltrials.gov, NCT00069329.

Keywords: adverse event (AE); anakinra; clinical trial; cryopyrin-associated periodic syndromes (CAPS); headache; infections; injection site reactions (ISR); neonatal-onset multisystem inflammatory disease (NOMID); safety.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adolescent
  • Adult
  • Antirheumatic Agents / administration & dosage
  • Antirheumatic Agents / adverse effects*
  • Arthralgia / chemically induced
  • Child
  • Child, Preschool
  • Cryopyrin-Associated Periodic Syndromes / drug therapy*
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Gastroenteritis / chemically induced
  • Headache Disorders / chemically induced
  • Humans
  • Injections, Subcutaneous
  • Interleukin 1 Receptor Antagonist Protein / administration & dosage
  • Interleukin 1 Receptor Antagonist Protein / adverse effects*
  • Male
  • Middle Aged
  • Patient Safety
  • Pneumonia / chemically induced
  • Prospective Studies
  • Treatment Outcome
  • Young Adult

Substances

  • Antirheumatic Agents
  • Interleukin 1 Receptor Antagonist Protein

Associated data

  • ClinicalTrials.gov/NCT00069329