Background/Purpose: Cryopyrin-Associated Periodic Syndromes (CAPS) include a group of rare inherited autoinflammatory diseases consisting of Familial Cold Autoinflammatory Syndrome (FCAS), Muckle-Wells Syndrome and the most severe form, Neonatal-Onset Multisystem Inflammatory Disease (NOMID). Data on the effect of anakinra on measures of central nervous system (CNS) inflammation and headaches have been reported in a broad range of severe CAPS patients, showing that headaches and cerebrospinal fluid (CSF) leukocytosis improved dramatically during anakinra treatment^1,2. The objective of this analysis is to evaluate the effect of anakinra on CNS inflammation and headache scores in CAPS children initiating anakinra treatment at an early age compared with adolescents/adults.

Methods: A prospective, open-label, long-term study of anakinra treatment in a total of 43 patients with severe CAPS was conducted at the National Institutes of Health^1,2. The patients were treated with anakinra for up to 5 years. CNS inflammation was evaluated with CSF white blood cell (WBC) count and magnetic resonance imaging (MRI) was used to characterize different CNS lesions (presence of leptomeningeal enhancement). Headaches were assessed daily with diaries and scored on a scale from 0 (no symptoms) to 4 (severe symptoms). The patients were classified as children (age <12 years) or adolescents/adults (age ≥12 years) based on age at anakinra treatment start, including subgroup analysis in infants/toddlers (age <2 years at treatment start). The changes from baseline in children versus adolescents/adults were compared using Mixed Model for Repeated Measures. References: ¹Goldbach-Mansky R, et al. NEJM. 2006;355:581-592.²Sibley CH, et al. Arthritis Rheum. 2012;64:2375-2386.

Results: Children (N=22) and adolescents/adults (N=8) presented with comparable symptoms at baseline, as assessed by CSF WBC count and presence of leptomeningeal enhancement as well as headache scores. For CSF WBC count and leptomeningeal enhancement, both children and adolescents/adults showed significant decreases from baseline and had comparable low values throughout the treatment period. The average (standard error) headache scores at baseline were 0.8 (0.2) for children and 1.1 (0.4) for adolescents/adults. Following the initiation of anakinra treatment, the headache scores decreased significantly. The decrease among children (average score of 0.1 or lower for up to Month 60) was larger than in adolescents/adults (average score of 0.3 to 0.6 at different visits); p=0.026. Among the 4 infants/toddlers, the headaches were present in 2 patients at baseline and decreased or disappeared during the treatment.

Conclusion: Both children and adolescents/adults presented with comparable CNS inflammation measures and headache scores at baseline. All measures improved after initiation of anakinra treatment and the headache scores decreased even more in children compared with adolescents/adults. The headaches decreased or disappeared in infants/toddlers with symptoms at baseline. These data further suggest that every effort should be made for early diagnosis and treatment initiation to preserve normal organ function in children with CAPS.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-effect-of-il-1-receptor-antagonist-anakinra-kineret-on-measures-of-central-nervous-system-inflammation-and-headaches-in-pediatric-patients-with-severe-cryopyrin-associated-periodic-syndrom/