PMID- 36356657 OWN - NLM STAT- MEDLINE DCOM- 20230411 LR - 20230614 IS - 1931-3543 (Electronic) IS - 0012-3692 (Print) IS - 0012-3692 (Linking) VI - 163 IP - 4 DP - 2023 Apr TI - Efzofitimod for the Treatment of Pulmonary Sarcoidosis. PG - 881-890 LID - S0012-3692(22)04053-3 [pii] LID - 10.1016/j.chest.2022.10.037 [doi] AB - 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. CI - Copyright (c) 2022 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Culver, Daniel A AU - Culver DA AD - Cleveland Clinic, Cleveland, OH. Electronic address: culverd@ccf.org. FAU - Aryal, Shambhu AU - Aryal S AD - Advanced Lung Disease and Lung Transplant Program, Inova Fairfax Hospital, Falls Church, VA. FAU - Barney, Joseph AU - Barney J AD - Department of Pulmonary and Critical Care Medicine, University of Alabama, Birmingham, AL. FAU - Hsia, Connie C W AU - Hsia CCW AD - Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX. FAU - James, W Ennis AU - James WE AD - Susan Pearlstine Sarcoidosis Center of Excellence, Pulmonary and Critical Care Medicine, Medical University of South Carolina, Charleston, SC. FAU - Maier, Lisa A AU - Maier LA AD - Division of Environmental and Occupational Health Sciences, National Jewish Health; Division of Pulmonary Sciences and Critical Care, Department of Medicine, School of Medicine, University of Colorado, Denver, CO. FAU - Marts, Lucian T AU - Marts LT AD - Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, GA. FAU - Obi, Ogugua Ndili AU - Obi ON AD - Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, Brody School of Medicine East Carolina University, Greenville, NC. FAU - Sporn, Peter H S AU - Sporn PHS AD - Division of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL. FAU - Sweiss, Nadera J AU - Sweiss NJ AD - Division of Rheumatology and Medical Director of the Arthritis Clinic, Chicago, IL; Bernie Mac Sarcoidosis Translational Advanced Research Center, University of Illinois College of Medicine, Chicago, IL. FAU - Shukla, Sanjay AU - Shukla S AD - aTyr Pharma, Inc., San Diego, CA. FAU - Kinnersley, Nelson AU - Kinnersley N AD - Octa Consulting Services, Ltd., Harpenden, England. FAU - Walker, Gennyne AU - Walker G AD - aTyr Pharma, Inc., San Diego, CA. FAU - Baughman, Robert AU - Baughman R AD - Department of Medicine, University of Cincinnati Medical Center, Cincinnati, OH. LA - eng SI - ClinicalTrials.gov/NCT03824392 GR - R01 HL140357/HL/NHLBI NIH HHS/United States GR - R01 HL142049/HL/NHLBI NIH HHS/United States GR - R01 HL136681/HL/NHLBI NIH HHS/United States GR - R13 HL142300/HL/NHLBI NIH HHS/United States GR - R01 HL131745/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20221108 PL - United States TA - Chest JT - Chest JID - 0231335 SB - IM MH - Humans MH - *Sarcoidosis, Pulmonary/drug therapy MH - Lung PMC - PMC10258437 OTO - NOTNLM OT - ATYR1923 OT - corticosteroids OT - efzofitimod OT - fatigue assessment scale OT - immunomodulator OT - lung function OT - neuropilin 2 OT - pulmonary sarcoidosis OT - quality of life OT - steroid taper EDAT- 2022/11/11 06:00 MHDA- 2023/04/11 06:42 PMCR- 2022/11/08 CRDT- 2022/11/10 19:23 PHST- 2022/07/11 00:00 [received] PHST- 2022/10/14 00:00 [revised] PHST- 2022/10/29 00:00 [accepted] PHST- 2023/04/11 06:42 [medline] PHST- 2022/11/11 06:00 [pubmed] PHST- 2022/11/10 19:23 [entrez] PHST- 2022/11/08 00:00 [pmc-release] AID - S0012-3692(22)04053-3 [pii] AID - 10.1016/j.chest.2022.10.037 [doi] PST - ppublish SO - Chest. 2023 Apr;163(4):881-890. doi: 10.1016/j.chest.2022.10.037. Epub 2022 Nov 8.