Background/Purpose: The autoinflammatory diseases (AIDs) are a group of disorders of the innate immune system characterized by seemingly unprovoked inflammation¹. A variety of genetic alterations are attributed to the clinical and pathological manifestations of these conditions; however, many of the patients presenting with clinical features of AIDs do not have a pathogenic mutation to be classified under one of the monogenic AIDs². These patients are referred to as having an undifferentiated autoinflammatory syndrome. Blocking of the interleukin 1 (IL-1) pathway is defined as a treatment modality in some of the AIDs (FMF, CAPS, TRAPS and MVK); but, there is limited data on their use in undifferentiated autoinflammatory syndromes.

Aim: We aim to review the treatment effects of the IL-1 receptor antagonist, anakinra, in pediatric undifferentiated autoinflammatory syndrome patients.

Methods: We identified the pediatric patients enrolled in the protocol 94-HG-0105 “Genetics and Pathophysiology of Familial Mediterranean Fever and Related Disorders” who were prescribed Anakinra between October 2010 and October 2016. Patients who tested positive for known genetic mutation to cause periodic fever syndromes (FMF, CAPS, TRAPS, MKD, PAPA, DIRA, HA20and DADA2) by commercially available methods were excluded. Medical records were reviewed to identify the response to treatment with Anakinra. Clinical response was determined based on the patient reported outcome. Laboratory data ((White Blood Cell Count (WBC), ESR and CRP)) were compared before and after the treatment. Statistical tests were done using RStudio (http://www.R-project.org). Clinical response to treatment were presented as frequency diagram. Laboratory data before and after the use of Anakinra was compared using the Wilcoxon signed rank test.

Results: We identified 75 patients who met the pre-specified criteria. Among the 75 patients, the majority of the patients were male (65%). The disease was predominantly seen among Caucasians (84%). Anakinra was prescribed as needed (PRN) for 56% of the patients, 44% required a daily dose. 59% of the patients were responders, 9% were partial responders and 17% did not have clinical response to the treatment. 13% of the patients were non-compliants, 1% could not tolerated and 1% of the patient did not have a follow up. Among the patients who had clinical response to treatment, we found a statistically significant decrease in ESR after treatment with anakinra (p-value = 0.01416, 95 percent confidence interval: 1.000085 8.999991).

Conclusion: The management of pediatric undifferentiated autoinflammatory syndromes is challenging. We found anakinra a very effective treatment option for use on both an intermittent and continuous basis. Anakinra has the potential to significantly improve the quality of life of such patients.

Refrences:

1. Kastner, Daniel L. “Hereditary periodic fever syndromes.” ASH Education Program Book 2005.1 (2005): 74-81.

2. Rigante, Donato, et al. “The hereditary autoinflammatory disorders uncovered.” Autoimmunity reviews 13.9 (2014): 892-900.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/interleukin-1-receptor-antagonist-is-a-potential-treatment-for-undifferentiated-autoinflammatory-syndromes/