THU0540 SYSTEMATIC REVIEW OF BIOLOGICAL TREATMENT OF DEFICIENCY OF INTERLEUKIN-36 RECEPTOR ANTAGONIST (DITRA) IN CHILDREN AND ADOLESCENTS
Authors: Toni Hospach, Fabian Glowatzki, Friederike Blankenburg, Dennis Conzelmann, Christian Strinkorb, Chris Sandra Muellerschoen, Peter Driesch von den, Lisa Koehler, Meino Rohlfs, Christoph Klein, Fabian Hauck
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Deficiency of interleukin-36 receptor antagonist (DITRA) is a life threatening autoinflammatory disease caused by autosomal recessive mutations of the <i>IL36RN</i> gene leading to recurrent episodes of generalized pustular psoriasis with systemic inflammation and fever. The disease is rare and no standardized treatment guidelines exist <h3>Objectives</h3> To systematically review and analyze the literature on biologically treated pediatric DITRA patients <h3>Methods</h3> A NCBI pubmed database research was performed to identify all relevant articles on pediatric DITRA patients treated with biologicals. According to defined response criteria therapeutic efficacy was analyzed. <h3>Results</h3> Our literature research revealed 13 pediatric patients with DITRA and biolocial treatment. Ten patients were homozygous including six with the p.Leu27Pro, three with the p.Arg10 Argfs* and one with the p.Thr123Met mutation and three were compound heterozygous. We add an unreported DITRA patient with a compound heterozygous <i>IL36RN</i> p.Pro76Leu/pSer113Leu mutation. In total 29 flares in 14 patients were treated with biological agents- targeting IL-1/R, IL-17, IL-12/23 and TNF-α. Complete response was achieved in 15 (52%), partial in 4 (14%), and no response in 10 (34%) of the flares. Response rates were heterogeneous among the different agents. While complete/partial/no response with inhibition of TNF-alpha could be achieved in 6 (46%)/3 (23%)/4 (31%), the inhibition of IL-17 and of IL-12/23 led in each 4 flares to a 100% complete response. IL-1/R inhibition led to complete/partial response in each 1 (13%) and was not effective in 6 (75%) flares. Of note, the unreported patient was successfully treated with weekly dosed adalimumab. <h3>Conclusion</h3> DITRA is a rare disease that has to be considered in patients with generalized pustular psoriasis with systemic inflammation and fever. It can be effectively treated with specific biological inhibition of TNF-alpha, IL-12/23 and IL- 17, while anti-IL-1/R treatment seems less effective. Weekly dosed adalimumab appears to be a novel treatment option for pediatric patients. Further reports and studies of biological treated pediatric DITRA patients are warranted for evaluation of optimal treatment. <h3>Reference</h3> [1] Marrakchi, S., P. Guigue, et al. (2011). "Interleukin-36-receptor antagonist deficiency and generalized pustular psoriasis." N Engl J Med 365(7): 620-628. <h3>Disclosure of Interests</h3> Toni Hospach Speakers bureau: Chugai, Roche, Novartis, Fabian Glowatzki: None declared, Friederike Blankenburg: None declared, Dennis Conzelmann: None declared, Christian Strinkorb: None declared, Chris Sandra Muellerschoen: None declared, Peter Driesch von den: None declared, Lisa Koehler: None declared, Meino Rohlfs: None declared, Christoph Klein: None declared, Fabian Hauck: None declared