Treatment with Elapegademase Restores Immunity in Infants with Adenosine Deaminase Deficient Severe Combined Immunodeficiency.
ADA-SCID
Adenosine deaminase deficiency
Elapegademase
Enzyme replacement therapy
Immune reconstitution
Severe combined immunodeficiency
Journal
Journal of clinical immunology
ISSN: 1573-2592
Titre abrégé: J Clin Immunol
Pays: Netherlands
ID NLM: 8102137
Informations de publication
Date de publication:
27 Apr 2024
27 Apr 2024
Historique:
received:
05
01
2024
accepted:
11
04
2024
medline:
28
4
2024
pubmed:
28
4
2024
entrez:
27
4
2024
Statut:
epublish
Résumé
Patients with adenosine deaminase 1 deficient severe combined immunodeficiency (ADA-SCID) are initially treated with enzyme replacement therapy (ERT) with polyethylene glycol-modified (PEGylated) ADA while awaiting definitive treatment with hematopoietic stem cell transplant (HSCT) or gene therapy. Beginning in 1990, ERT was performed with PEGylated bovine intestinal ADA (ADAGEN®). In 2019, a PEGylated recombinant bovine ADA (Revcovi®) replaced ADAGEN following studies in older patients previously treated with ADAGEN for many years. There are limited longitudinal data on ERT-naïve newborns treated with Revcovi. We report our clinical experience with Revcovi as initial bridge therapy in three newly diagnosed infants with ADA-SCID, along with comprehensive biochemical and immunologic data. Revcovi was initiated at twice weekly dosing (0.2 mg/kg intramuscularly), and monitored by following plasma ADA activity and the concentration of total deoxyadenosine nucleotides (dAXP) in erythrocytes. All patients rapidly achieved a biochemically effective level of plasma ADA activity, and red cell dAXP were eliminated within 2-3 months. Two patients reconstituted B-cells and NK-cells within the first month of ERT, followed by naive T-cells one month later. The third patient reconstituted all lymphocyte subsets within the first month of ERT. One patient experienced declining lymphocyte counts with improvement following Revcovi dose escalation. Two patients developed early, self-resolving thrombocytosis, but no thromboembolic events occurred. Revcovi was safe and effective as initial therapy to restore immune function in these newly diagnosed infants with ADA-SCID, however, time course and degree of reconstitution varied. Revcovi dose may need to be optimized based on immune reconstitution, clinical status, and biochemical data.
Identifiants
pubmed: 38676811
doi: 10.1007/s10875-024-01710-z
pii: 10.1007/s10875-024-01710-z
doi:
Substances chimiques
Adenosine Deaminase
EC 3.5.4.4
pegademase bovine
HW3H7D91F6
Recombinant Proteins
0
Types de publication
Journal Article
Case Reports
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
107Subventions
Organisme : NIH T32 Training Grant
ID : T32AI007062
Organisme : NIH T32 Training Grant
ID : T32AI007062
Informations de copyright
© 2024. The Author(s).
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