Chest · 2022
Efzofitimod for the Treatment of Pulmonary Sarcoidosis.
Рандомизированное исследованиеСтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Culver Daniel A, Aryal Shambhu, Barney Joseph, Hsia Connie C W, James W Ennis, Maier Lisa A, Marts Lucian T, Obi Ogugua Ndili, Sporn Peter H S, Sweiss Nadera J, Shukla Sanjay, Kinnersley Nelson, Walker Gennyne, Baughman Robert
Аннотация
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.
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.