Efzofitimod for the Treatment of Pulmonary Sarcoidosis.
ATYR1923
corticosteroids
efzofitimod
fatigue assessment scale
immunomodulator
lung function
neuropilin 2
pulmonary sarcoidosis
quality of life
steroid taper
Journal
Chest
ISSN: 1931-3543
Titre abrégé: Chest
Pays: United States
ID NLM: 0231335
Informations de publication
Date de publication:
04 2023
04 2023
Historique:
received:
11
07
2022
revised:
14
10
2022
accepted:
29
10
2022
medline:
11
4
2023
pubmed:
11
11
2022
entrez:
10
11
2022
Statut:
ppublish
Résumé
Pulmonary sarcoidosis is characterized by the accumulation of immune cells that form granulomas affecting the lungs. Efzofitimod (ATYR1923), a novel immunomodulator, selectively binds neuropilin 2, which is upregulated on immune cells in response to lung inflammation. What is the tolerability, safety, and effect on outcomes of efzofitimod in pulmonary sarcoidosis? In this randomized, double-blind, placebo-controlled study evaluating multiple ascending doses of efzofitimod administered intravenously every 4 weeks for 24 weeks, randomized patients (2:1) underwent a steroid taper to 5 mg/d by week 8 or < 5 mg/d after week 16. The primary end point was the incidence of adverse events (AEs); secondary end points included steroid reduction, change in lung function, and patient-reported outcomes on health-related quality-of-life scales. Thirty-seven patients received at least one dose of study medication. Efzofitimod was well tolerated at all doses, with no new or unexpected AEs and no dose-dependent AE incidence. Average daily steroid doses through end of study were 6.8 mg, 6.5 mg, and 5.6 mg for the 1 mg/kg, 3 mg/kg, and 5 mg/kg groups compared with 7.2 mg for placebo, resulting in a baseline-adjusted relative steroid reduction of 5%, 9%, and 22%, respectively. Clinically meaningful improvements were achieved across several patient-reported outcomes, several of which reached statistical significance in the 5 mg/kg dose arm. A dose-dependent but nonsignificant trend toward improved lung function also was observed for 3 and 5 mg/kg. Efzofitimod was safe and well tolerated and was associated with dose-dependent improvements of several clinically relevant end points compared with placebo. The results of this study support further evaluation of efzofitimod in pulmonary sarcoidosis. ClinicalTrials.gov; No.: NCT03824392; URL: www. gov.
Sections du résumé
BACKGROUND
Pulmonary sarcoidosis is characterized by the accumulation of immune cells that form granulomas affecting the lungs. Efzofitimod (ATYR1923), a novel immunomodulator, selectively binds neuropilin 2, which is upregulated on immune cells in response to lung inflammation.
RESEARCH QUESTION
What is the tolerability, safety, and effect on outcomes of efzofitimod in pulmonary sarcoidosis?
STUDY DESIGN AND METHODS
In this randomized, double-blind, placebo-controlled study evaluating multiple ascending doses of efzofitimod administered intravenously every 4 weeks for 24 weeks, randomized patients (2:1) underwent a steroid taper to 5 mg/d by week 8 or < 5 mg/d after week 16. The primary end point was the incidence of adverse events (AEs); secondary end points included steroid reduction, change in lung function, and patient-reported outcomes on health-related quality-of-life scales.
RESULTS
Thirty-seven patients received at least one dose of study medication. Efzofitimod was well tolerated at all doses, with no new or unexpected AEs and no dose-dependent AE incidence. Average daily steroid doses through end of study were 6.8 mg, 6.5 mg, and 5.6 mg for the 1 mg/kg, 3 mg/kg, and 5 mg/kg groups compared with 7.2 mg for placebo, resulting in a baseline-adjusted relative steroid reduction of 5%, 9%, and 22%, respectively. Clinically meaningful improvements were achieved across several patient-reported outcomes, several of which reached statistical significance in the 5 mg/kg dose arm. A dose-dependent but nonsignificant trend toward improved lung function also was observed for 3 and 5 mg/kg.
INTERPRETATION
Efzofitimod was safe and well tolerated and was associated with dose-dependent improvements of several clinically relevant end points compared with placebo. The results of this study support further evaluation of efzofitimod in pulmonary sarcoidosis.
TRIAL REGISTRY
ClinicalTrials.gov; No.: NCT03824392; URL: www.
CLINICALTRIALS
gov.
Identifiants
pubmed: 36356657
pii: S0012-3692(22)04053-3
doi: 10.1016/j.chest.2022.10.037
pmc: PMC10258437
pii:
doi:
Banques de données
ClinicalTrials.gov
['NCT03824392']
Types de publication
Randomized Controlled Trial
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
881-890Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL140357
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL142049
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL136681
Pays : United States
Organisme : NHLBI NIH HHS
ID : R13 HL142300
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL131745
Pays : United States
Informations de copyright
Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.
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