Anti-tumour necrosis factor treatment for the prevention of ischaemic events in patients with deficiency of adenosine deaminase 2 (DADA2).
Level 4 - case-series / case-control
Retrospective before-and-after case series without a concurrent control group
PubMed 33420503 · doi:10.1093/rheumatology/keaa837
What was done
A retrospective before-and-after analysis was conducted on 31 patients with genetically confirmed deficiency of adenosine deaminase 2 (DADA2) referred from six centres to Great Ormond Street Hospital. Ischaemic events (CNS and non-CNS), vasculitic disease activity (Paediatric Vasculitis Activity Score, PVAS), and biochemical, immunological, and radiological features were evaluated and compared before and after anti-TNF treatment (received by 27 patients for a median of 32 months).
What was found
The median rate of ischemic events decreased from 2.37 per 100 patient-months (IQR 1.25–3.63) prior to anti-TNF therapy to 0.00 per 100 patient-months (IQR 0.0–0.0) following treatment (p < 0.0001). Vasculitis disease activity on the PVAS decreased from a median of 20/63 (IQR 13.0–25.8) pre-treatment to 2/63 (IQR 0.0–3.8) post-treatment (p < 0.0001), with mild livedoid rash remaining as the main persistent feature. Anti-TNF therapy showed no efficacy for severe immunodeficiency or bone marrow failure, which necessitated haematopoietic stem cell transplantation.
Why it matters
These findings provide strong observational evidence that anti-TNF agents effectively control vasculopathy and halt stroke and other ischemic complications in DADA2, while clarifying that haematopoietic stem cell transplantation remains necessary for hematological and immunodeficiency manifestations.
Limits
The study is limited by its retrospective design, small sample size (n = 31, with 27 treated), and reliance on historical within-patient controls rather than a concurrent comparator group. Details regarding specific anti-TNF agents and dosing regimens were not specified in the abstract.