Long-term safety profile of anakinra in patients with severe cryopyrin-associated periodic syndromes

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.

Fig. 1

Exposure per dose level in the study population Exposure per dose level (daily s.c. dose).

Fig. 2

Adverse event rates by age group and over time (A) Yearly event rate by age at onset for the safety population (n = 43) in infants (<2 years), children (2–11 years), adolescents (12–17 years) and adults (≥18 years). (B) Adverse event rate over time during the study period. In the line representing non-CAPS related AEs the following AEs were excluded: ocular hyperaemia pyrexia, fatigue, malaise, arthralgia, headache, dizziness, rash and urticaria.