Pos0863 Real-Life Data Comparing the Long-Term Outcome and Treatment in Adult and Pediatric Dada2 Patients: Single Center Experience Over 10 Years

Background: The deficiency of adenosine deaminase 2 enzyme (DADA2), a hereditary autoinflammatory condition due ADA2 enzyme deficiency, disrupts vascular integrity, increases proinflammatory macrophages, and triggers vascular inflammation via tumor necrosis factor (TNF). Objectives: Investigating real-world outcomes, our focus is on anti-TNF agents as a primary treatment for individuals with DADA2, acknowledging TNF's pivotal role in the disease. Methods: This descriptive analysis encompassed all adult and pediatric patients with DADA2 from our Vasculitis Research Centre prospective database. We documented demographics, clinical features, and treatment specifics. Among the entire cohort, we specifically examined patients who underwent anti-TNF therapy, analyzing the treatment duration, dosage, indications, and outcomes. Physicians' assessments determined treatment responses, categorized as full response (symptom-free state with normal acute phase reactants) or partial/no response. If applicable, available information on the reasons for patient deaths was also investigated. Results: A total of 32 patients (adult/pediatric, n=19/13) were analyzed. The mean (SD) current age of the living patients was 27.4 (8.5) years in adults and 11.2 (3.5) years in children. The mean age at diagnosis was 14.9 (9.2) years. The G47R mutation was homozygous in 25/27 (92.5%) and heterozygous in 2/27 (7.4%) of the patients. 28 of the 32 patients were prescribed anti-TNF agents (etanercept, n=26; adalimumab, n=2) (Table 1). During the median (IQR) 60 (66) months of follow-up on anti-TNF treatment, 10 (35.7%) of the patients showed a complete response. Patients with a complete response had received anti-TNF agents for predominant nervous system involvement (n=6), renal involvement (n=1), constitutional symptoms (n=1) or skin involvement (n=3). Nine, patients (32.1%) had a partial response and in 3 patients the outcome was not available. Two patients underwent bone marrow transplantation, with one patient dying and the other being cured and off treatment. Of the patients who received anti-TNF treatment, 20/28 are still on treatment. 13/20 (65%) patients are currently receiving tapered anti-TNF treatment according to their physician's decision. The first patient was diagnosed in 2013 and in the last 10 years 6/32 (18.75%) of the patients have died. Five out of 6 deceased patients received TNFi: One patient with haematological involvement did not respond to anti-TNF and died after bone marrow transplantation. The other patient died in 2015 after 3 months of anti-TNF. In one patient, anti-TNF was discontinued due to cardiomyopathy. One patient had resistant digital necrosis the last patient had a novel mutation with both haematological/immunological and neurological involvement, both died of sepsis. Conclusion: In conclusion, although anti-TNF drugs are the main treatment for DADA2, hematological involvement does not respond. The clinical course of patients is diverse, with a mortality rate of up to 20% over a 10-year period. However, in certain instances, treatment tapering may be feasible, emphasizing the need for individualized decision-making in patient management. REFERENCES: NIL. Table 1. Demographic and clinical characteristics of patients Acknowledgements: First two authors have equally contributed. Disclosure of Interests: None declared.