Background Deficiency in interleukin-1 (IL-1) receptor (IL-R) antagonist (DIRA) is a rare genetic autoinflammatory disorder resulting from autsomal recessive mutations in the IL1RN gene. The use of IL-1 antagonists may prove to be a valid therapeutic alternative, but there is a lack of secondary studies that summarise the use of IL-1-targeting agents in this disease.

Purpose To summarise the efficacy and safety of IL-1 antagonist drugs in DIRA following the scoping review’s methodology.

Material and methods The study was conducted and reported using the methodology described in the Joanna Briggs Institute Reviewer’s Manual¹ and the PRISMA Extension for Scoping Reviews.²

Results Fifteen case reports studies describing 19 DIRA patients between 2009 and 2017 were found. Nine different mutations in IL1RN were described, showing a homozygous genotype in all cases. Pustular dermatitis and localised swelling represented the most frequent symptom of onset of the disease. These patients were previously treated with corticosteroids (n=13), antibiotics (n=12), NSAIDs (n=4), antifungals (n=3), acitretin (n=3) and, to a lesser frequency, with immunomodulatory drugs (methotrexate, cyclosporine, intravenous immunoglobulins, azathioprine, thalidomide or etanercept). The length of therapy with anakinra (n=17) and canakinumab (n=2) varied between 2 weeks and 4.5 years. All patients achieved immediate (day-hours) clinical responses and most patients also showed good clinical responses in the short (<12 weeks) (n=15) and medium-long (>24 weeks) (n=10) term. In the two patients treated with canakinumab, one showed good overall response, and the other required a dose increase to achieve a good response in the short term with no data available in the medium/long-term. With respect to drug safety, anakinra was associated with transient injection site reactions (n=3) and anaphylactic reactions (n=2). Discontinuation of anakinra in nine patients was reported following a flare-up of their disease. An episode of vomiting and diarrhoea was reported in a patient treated with high doses of canakinumab.

Conclusion The observed efficacy was high in patients with DIRA at all times, both with anakinra and canakinumab. However, evidence is scarce and of low quality, thus larger studies need to be conducted to reach more accurate conclusions.

References and/or acknowledgements 1. The Joanna Briggs Institute. The Joanna Briggs Institute Reviewer’s Manual 2015. http://joannabriggs.org/assets/docs/sumari/Reviewers-Manual_Methodology-for-JBI-Scoping-Reviews_2015_v2.pdf (accessed 29 Sept 2018.)

2. PRISMA Extension for Scoping Reviews (PRISMA-ScR): Checklist and explanation. http://annals.org/aim/fullarticle/2700389/prisma-extension-scoping-reviews-prisma-scr-checklist-explanation (accessed 29 Sept 2018.)

No conflict of interest.