PMID- 33420503 OWN - NLM STAT- MEDLINE DCOM- 20211004 LR - 20211004 IS - 1462-0332 (Electronic) IS - 1462-0324 (Linking) VI - 60 IP - 9 DP - 2021 Sep 1 TI - Anti-tumour necrosis factor treatment for the prevention of ischaemic events in patients with deficiency of adenosine deaminase 2 (DADA2). PG - 4373-4378 LID - 10.1093/rheumatology/keaa837 [doi] AB - OBJECTIVE: To evaluate the impact of anti-Tumour Necrosis Factor-alpha (anti-TNF) treatment on the occurrence of vasculitic ischaemic events in patients with deficiency of adenosine deaminase 2 (DADA2). METHODS: A retrospective analysis of DADA2 patients referred from six centres to Great Ormond Street Hospital for Children was conducted. Ischaemic events, vasculitic disease activity, biochemical, immunological, and radiological features were compared, before and after anti-TNF treatment. RESULTS: A total of 31 patients with genetically confirmed DADA2 were included in the study. The median duration of active disease activity prior to anti-TNF treatment was 73 months (inter-quartile range [IQR] 27.5-133.5 months). Twenty seven/31 patients received anti-TNF treatment for a median of 32 months (IQR 12.0-71.5 months). The median event rate of central nervous system (CNS) and non-CNS ischemic events before anti-TNF treatment was 2.37 per 100 patient-months (IQR 1.25-3.63); compared with 0.00 per 100 patient-months (IQR 0.0-0.0) post-treatment (p< 0.0001). Paediatric vasculitis activity score (PVAS) was also significantly reduced: median score of 20/63 (IQR 13.0-25.8/63) pre-treatment vs. 2/63 (IQR 0.0-3.8/63) following anti-TNF treatment (p< 0.0001), with mild livedoid rash being the main persisting feature. Anti-TNF treatment was not effective for severe immunodeficiency or bone marrow failure, which required haematopoietic stem cell transplantation (HSCT). CONCLUSION: Anti-TNF treatment significantly reduced the incidence of ischaemic events and other vasculitic manifestations of DADA2, but was not effective for immunodeficiency or bone marrow failure. CI - (c) The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com. FAU - Cooray, Samantha AU - Cooray S AD - Infection, Inflammation and Rheumatology Section, University College London Great Ormond Street Institute of Child Health, London. FAU - Omyinmi, Ebun AU - Omyinmi E AD - Infection, Inflammation and Rheumatology Section, University College London Great Ormond Street Institute of Child Health, London. FAU - Hong, Ying AU - Hong Y AD - Infection, Inflammation and Rheumatology Section, University College London Great Ormond Street Institute of Child Health, London. FAU - Papadopoulou, Charalampia AU - Papadopoulou C AD - Infection, Inflammation and Rheumatology Section, University College London Great Ormond Street Institute of Child Health, London. FAU - Harper, Lorraine AU - Harper L AD - Institute of Applied Health Research, University of Birmingham. FAU - Al-Abadi, Eslam AU - Al-Abadi E AD - Rheumatology Department, Birmingham Women's and Children's NHS Foundation Trust, Birmingham. FAU - Goel, Ruchika AU - Goel R AD - Institute of Applied Health Research, University of Birmingham. FAU - Dubey, Shirish AU - Dubey S AD - Rheumatology Department, Oxford University Hospitals NHS Foundation Trust, Oxford. FAU - Wood, Mark AU - Wood M AD - Paediatric Rheumatology Department, Leeds Teaching Hospitals NHS Trust, Leeds. FAU - Jolles, Stephen AU - Jolles S AD - Department of Immunology, University Hospital of Wales, Cardiff, UK. FAU - Berg, Stefan AU - Berg S AD - Paediatric Rheumatology, The Queen Silvia Children's Hospital and University of Gothenburg, Gothenburg. FAU - Ekelund, Maria AU - Ekelund M AD - Ryhov County Hospital, Jonkoping, Sweden. FAU - Armon, Kate AU - Armon K AD - Department of Paediatric Rheumatology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK. FAU - Eleftheriou, Despina AU - Eleftheriou D AD - Infection, Inflammation and Rheumatology Section, University College London Great Ormond Street Institute of Child Health, London. FAU - Brogan, Paul A AU - Brogan PA AD - Infection, Inflammation and Rheumatology Section, University College London Great Ormond Street Institute of Child Health, London. LA - eng GR - 21791/VAC_/Versus Arthritis/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Rheumatology (Oxford) JT - Rheumatology (Oxford, England) JID - 100883501 RN - 0 (Intercellular Signaling Peptides and Proteins) RN - 0 (Tumor Necrosis Factor Inhibitors) RN - EC 3.5.4.4 (ADA2 protein, human) RN - EC 3.5.4.4 (Adenosine Deaminase) RN - Severe combined immunodeficiency due to adenosine deaminase deficiency SB - IM CIN - Rheumatology (Oxford). 2021 Jun 18;60(6):e218-e219. PMID: 33515254 MH - Adenosine Deaminase/*genetics MH - Adolescent MH - Agammaglobulinemia/complications/*genetics MH - Female MH - Humans MH - Intercellular Signaling Peptides and Proteins/*genetics MH - Ischemia/etiology/*prevention & control MH - Male MH - Mutation MH - Phenotype MH - Retrospective Studies MH - Severe Combined Immunodeficiency/complications/*genetics MH - Tumor Necrosis Factor Inhibitors/*therapeutic use OTO - NOTNLM OT - DADA2 OT - PVAS OT - anti-TNF OT - inflammation OT - ischaemia OT - stroke OT - vasculitis EDAT- 2021/01/10 06:00 MHDA- 2021/10/05 06:00 CRDT- 2021/01/09 05:49 PHST- 2020/10/08 00:00 [received] PHST- 2020/11/12 00:00 [revised] PHST- 2021/01/10 06:00 [pubmed] PHST- 2021/10/05 06:00 [medline] PHST- 2021/01/09 05:49 [entrez] AID - 6071499 [pii] AID - 10.1093/rheumatology/keaa837 [doi] PST - ppublish SO - Rheumatology (Oxford). 2021 Sep 1;60(9):4373-4378. doi: 10.1093/rheumatology/keaa837.