PMID- 37338154 OWN - NLM STAT- MEDLINE DCOM- 20231023 LR - 20240409 IS - 1365-2249 (Electronic) IS - 0009-9104 (Print) IS - 0009-9104 (Linking) VI - 213 IP - 3 DP - 2023 Oct 13 TI - Efficacy and safety of MAS825 (anti-IL-1beta/IL-18) in COVID-19 patients with pneumonia and impaired respiratory function. PG - 265-275 LID - 10.1093/cei/uxad065 [doi] AB - MAS825, a bispecific IL-1beta/IL-18 monoclonal antibody, could improve clinical outcomes in COVID-19 pneumonia by reducing inflammasome-mediated inflammation. Hospitalized non-ventilated patients with COVID-19 pneumonia (n = 138) were randomized (1:1) to receive MAS825 (10 mg/kg single i.v.) or placebo in addition to standard of care (SoC). The primary endpoint was the composite Acute Physiology and Chronic Health Evaluation II (APACHE II) score on Day 15 or on the day of discharge (whichever was earlier) with worst-case imputation for death. Other study endpoints included safety, C-reactive protein (CRP), SARS-CoV-2 presence, and inflammatory markers. On Day 15, the APACHE II score was 14.5 +/- 1.87 and 13.5 +/- 1.8 in the MAS825 and placebo groups, respectively (P = 0.33). MAS825 + SoC led to 33% relative reduction in intensive care unit (ICU) admissions, ~1 day reduction in ICU stay, reduction in mean duration of oxygen support (13.5 versus 14.3 days), and earlier clearance of virus on Day 15 versus placebo + SoC group. On Day 15, compared with placebo group, patients treated with MAS825 + SoC showed a 51% decrease in CRP levels, 42% lower IL-6 levels, 19% decrease in neutrophil levels, and 16% lower interferon-gamma levels, indicative of IL-1beta and IL-18 pathway engagement. MAS825 + SoC did not improve APACHE II score in hospitalized patients with severe COVID-19 pneumonia; however, it inhibited relevant clinical and inflammatory pathway biomarkers and resulted in faster virus clearance versus placebo + SoC. MAS825 used in conjunction with SoC was well tolerated. None of the adverse events (AEs) or serious AEs were treatment-related. CI - Published by Oxford University Press on behalf of the British Society for Immunology 2023. FAU - Hakim, Alex D AU - Hakim AD AD - Providence Little Company of Mary Medical Center, Torrance, CA, USA. FAU - Awili, Mustafa AU - Awili M AD - Dallas Regional Medical Center, Mesquite, TX, USA. FAU - O'Neal, Hollis R AU - O'Neal HR AD - Louisiana State University Health Sciences Center and Our Lady of the Lake Regional Medical Center, Baton Rouge, LA, USA. FAU - Siddiqi, Omar AU - Siddiqi O AD - Boston Medical Center, Boston, MA, USA. FAU - Jaffrani, Naseem AU - Jaffrani N AD - Rapides Regional Medical Center, Alexandria, LA, USA. FAU - Lee, Richard AU - Lee R AD - University of California, Irvine, CA, USA. FAU - Overcash, Jeffrey S AU - Overcash JS AD - Sharp Grossmont Hospital, La Mesa, CA, USA. FAU - Chauffe, Ann AU - Chauffe A AD - Louisiana State University Health Sciences Center, Lafayette, LA, USA. FAU - Hammond, Terese C AU - Hammond TC AD - Saint Johns Cancer Institute, Santa Monica, CA, USA. FAU - Patel, Bela AU - Patel B AD - University of Texas McGovern Medical School, Houston, TX, US. FAU - Waters, Michael AU - Waters M AD - Sharp Chula Vista Medical Center, Chula Vista, CA, USA. FAU - Criner, Gerard J AU - Criner GJ AD - Department of Thoracic Medicine and Surgery, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA. FAU - Pachori, Alok AU - Pachori A AD - MorphoSys AG, Boston, MA, USA. FAU - Junge, Guido AU - Junge G AD - Novartis Pharma AG, Basel, Switzerland. FAU - Levitch, Rafael AU - Levitch R AD - Novartis Pharma AG, Basel, Switzerland. FAU - Watts, Jen AU - Watts J AD - Oculis, Boston, MA, USA. FAU - Koo, Philip AU - Koo P AD - Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA. FAU - Sengupta, Tirtha AU - Sengupta T AD - Novartis Healthcare Pvt Ltd, Hi-Tech City, Hyderabad, India. FAU - Yu, Lili AU - Yu L AD - Novartis Institutes for BioMedical Research, Cambridge, MA, USA. FAU - Kiffe, Michael AU - Kiffe M AD - Novartis Institutes for BioMedical Research, Basel, Switzerland. FAU - Pinck, Anne AU - Pinck A AD - Novartis Institutes for BioMedical Research, Basel, Switzerland. FAU - Stein, Richard R AU - Stein RR AD - Novartis Institutes for BioMedical Research, Basel, Switzerland. FAU - Bendrick-Peart, Jamie AU - Bendrick-Peart J AD - Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA. FAU - Jenkins, Janet AU - Jenkins J AD - Novartis Institutes for BioMedical Research, Cambridge, MA, USA. FAU - Rowlands, Marianna AU - Rowlands M AD - Novartis Institutes for BioMedical Research, Cambridge, MA, USA. FAU - Waldron-Lynch, Frank AU - Waldron-Lynch F AD - Novartis Institutes for BioMedical Research, Cambridge, MA, USA. FAU - Matthews, Jesse AU - Matthews J AD - Hospital Medicine, St Charles Health System, Bend, OR, USA. LA - eng SI - ClinicalTrials.gov/NCT04382651 GR - Novartis Pharma AG/ PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - England TA - Clin Exp Immunol JT - Clinical and experimental immunology JID - 0057202 RN - 0 (Interleukin-18) SB - IM MH - Humans MH - *COVID-19 MH - SARS-CoV-2 MH - Interleukin-18 MH - Inflammation MH - Hospitalization MH - Treatment Outcome PMC - PMC10570997 OTO - NOTNLM OT - COVID-19 OT - MAS825 OT - efficacy and safety OT - impaired respiratory function OT - pneumonia COIS- JSO reports research funding from Novartis, paid to his institution. AP was a former employee of Novartis and reports stock and stock options from Novartis AG and MorphoSys AG. PK was a former employee of Novartis Pharmaceuticals Corporation and reports stock from Novartis Pharmaceuticals Corporation during the conduct of the study and stocks from Bristol Myers Squibb after the conduct of the study but prior to publication. MK and RRS reports patents relevant to their work and RRS is an employee of Novartis Institutes for BioMedical Research (Basel). GJ and RL are employees of Novartis Pharma AG. JW and JBP are employees of Novartis Pharmaceuticals Corporation. TS is an employee of Novartis Healthcare Pvt Ltd. LY, JJ, and MR are employees of Novartis Institutes for BioMedical Research (Cambridge). MK and AP are employees of Novartis Institutes for BioMedical Research (Basel). FWL was a former employee of Novartis Institutes for BioMedical Research (Cambridge). ADH, MA, HON, OS, NJ, RL, AC, HT, BP, MW, GJC, and JM reports no confict of interest. EDAT- 2023/06/20 13:10 MHDA- 2023/10/23 00:44 PMCR- 2023/06/20 CRDT- 2023/06/20 08:23 PHST- 2022/07/18 00:00 [received] PHST- 2023/03/02 00:00 [revised] PHST- 2023/06/19 00:00 [accepted] PHST- 2023/10/23 00:44 [medline] PHST- 2023/06/20 13:10 [pubmed] PHST- 2023/06/20 08:23 [entrez] PHST- 2023/06/20 00:00 [pmc-release] AID - 7203697 [pii] AID - uxad065 [pii] AID - 10.1093/cei/uxad065 [doi] PST - ppublish SO - Clin Exp Immunol. 2023 Oct 13;213(3):265-275. doi: 10.1093/cei/uxad065.