THU0540 SYSTEMATIC REVIEW OF BIOLOGICAL TREATMENT OF DEFICIENCY OF INTERLEUKIN-36 RECEPTOR ANTAGONIST (DITRA) IN CHILDREN AND ADOLESCENTS

Abstract

Background: Deficiency of interleukin-36 receptor antagonist (DITRA) is a life threatening autoinflammatory disease caused by autosomal recessive mutations of the IL36RN gene leading to recurrent episodes of generalized pustular psoriasis with systemic inflammation and fever. The disease is rare and no standardized treatment guidelines exist Objectives: To systematically review and analyze the literature on biologically treated pediatric DITRA patients Methods: 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. Results: 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 IL36RN 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-αlpha 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. Conclusion: 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-αlpha, 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.