Inhibition of complement C1s improves severe hemolytic anemia in cold agglutinin disease: a first-in-human trial.
Aged
Anemia, Hemolytic
/ etiology
Anemia, Hemolytic, Autoimmune
/ complications
Antibodies, Monoclonal, Humanized
/ therapeutic use
Complement C1s
/ antagonists & inhibitors
Female
Follow-Up Studies
Hemolysis
/ drug effects
Humans
Male
Middle Aged
Prognosis
Prospective Studies
Severity of Illness Index
Journal
Blood
ISSN: 1528-0020
Titre abrégé: Blood
Pays: United States
ID NLM: 7603509
Informations de publication
Date de publication:
28 02 2019
28 02 2019
Historique:
received:
08
06
2018
accepted:
09
10
2018
pubmed:
19
12
2018
medline:
13
11
2019
entrez:
19
12
2018
Statut:
ppublish
Résumé
Cold agglutinin disease is a difficult-to-treat autoimmune hemolytic anemia in which immunoglobulin M antibodies bind to erythrocytes and fix complement, resulting in predominantly extravascular hemolysis. This trial tested the hypothesis that the anti-C1s antibody sutimlimab would ameliorate hemolytic anemia. Ten patients with cold agglutinin disease participated in the phase 1b component of a first-in-human trial. Patients received a test dose of 10-mg/kg sutimlimab followed by a full dose of 60 mg/kg 1 to 4 days later and 3 additional weekly doses of 60 mg/kg. All infusions were well tolerated without premedication. No drug-related serious adverse events were observed. Seven of 10 patients with cold agglutinin disease responded with a hemoglobin increase >2 g/dL. Sutimlimab rapidly increased hemoglobin levels by a median of 1.6 g/dL within the first week, and by a median of 3.9 g/dL (interquartile range, 1.3-4.5 g/dL; 95% confidence interval, 2.1-4.5) within 6 weeks (
Identifiants
pubmed: 30559259
pii: S0006-4971(20)42742-9
doi: 10.1182/blood-2018-06-856930
pmc: PMC6396179
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Complement C1s
EC 3.4.21.42
sutimlimab
GNWE7KJ995
Banques de données
ClinicalTrials.gov
['NCT02502903']
Types de publication
Clinical Trial, Phase I
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
893-901Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2019 by The American Society of Hematology.
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