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CO0001 MAVRILIMUMAB IMPROVES OUTCOMES IN SEVERE COVID-19 PNEUMONIA AND SYSTEMIC HYPER-INFLAMMATION

2020; BMJ; Volume: 79; Issue: Suppl 1 Linguagem: Inglês

10.1136/annrheumdis-2020-eular.6858

1468-2060

Giacomo De Luca, Giulio Cavalli, Corrado Campochiaro, Emanuel Della‐Torre, Piera Angelillo, Alessandro Tomelleri, Nicola Boffini, Stefano Tentori, F. Mette, Patrizia Rovere‐Querini, Annalisa Ruggeri, Teresa D’Aliberti, P. Scarpelllini, Giovanni Landoni, Francesco De Cobelli, John F. Paolini, Alberto Zangrillo, Moreno Tresoldi, Bruce C. Trapnell, Fabio Ciceri, Lorenzo Dagna,

SARS-CoV-2 and COVID-19 Research

Background: Patients with severe COVID-19 pneumonia and hyperinflammation face increased mortality. There is an urgent need for effective treatments to reduce the burden of the COVID-19 pandemic. Objectives: Our protocol aimed at evaluating the potential improvement in clinical outcomes with mavrilimumab, an anti-Granulocyte/Macrophage Colony-Stimulating Factor Receptor alpha (GM-CSFRα) monoclonal antibody, in patients with COVID-19 pneumonia and systemic hyper-inflammation. Methods: Single-center, open-label, single active arm intervention; Adult patients with severe COVID-19 pneumonia (as evaluated by CT scanning), hypoxia (PaO2:FiO2 ratio ≤ 300 mmHg), and systemic hyper-inflammation (increased C-reactive protein [CRP] ≥ 100 mg/mL and/or ferritin ≥ 900 μg/L, increased lactate dehydrogenase [LDH]) received a single intravenous dose of mavrilimumab added to standard of care; follow-up 28 days. Main outcomes measure was time to clinical improvement (reduction ≥ 2 categories on the 7-point WHO clinical status scale, 1=discharge, 7=death); others included time to discharge from hospital; % of pts achieving a clinical improvement; survival; mechanical-ventilation free survival; time to fever resolution; CRP; PaO2:FiO2 ratio. Results: A mavrilimumab group (n=13 COVID-19 patients, non-mechanically ventilated, median age 57 [IQR, 52-58], males 12 [92%], febrile 11 [85%]; PaO 2 :FiO 2 195.5[166.7–215.0]) was compared to a cohort of 26 contemporaneous patients with similar baseline characteristics. Death occurred in 0% (n=0/13) of mavrilimumab recipients and 27% (n=7/26) of comparison-group patients (log rank p=0.046) during the 28-day follow-up. 100% (n=13) of mavrilimumab recipients and 65% (n=17) of comparison-group patients achieved clinical improvement (p=0.018) at Day 28, with earlier improvement (median 8.0 [IQR, 5.0–11.0] days vs 18.5 [11.0–NE] days) (p<0.001) in mavrilimumab recipients. Fever had resolved in 91% (n=10/11 febrile patients) of mavrilimumab recipients by Day 14, compared to 61% (n=11/18 febrile) of patients in the comparison group (p=0.110); fever resolution was faster in mavrilimumab recipients versus controls (median 1.0 [IQR, 1.0–2.0] day vs 7.0 [3.0 - NE] days, respectively, p=0·009). Mavrilimumab was well tolerated in all patients. Conclusion: Patients with severe COVID-19 pneumonia and systemic hyper-inflammation who received treatment with mavrilimumab had better clinical outcomes compared to patients receiving routine care. Mavrilimumab was well-tolerated. Randomized controlled trials are warranted to confirm our findings. References: [1]Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020;395:1054-62 [2]Mehta P, McAuley DF, Brown M, et al. HLH Across Speciality Collaboration, UK. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395:1033-4 Disclosure of Interests: Giacomo De Luca Speakers bureau: SOBI, Novartis, Celgene, Pfizer, MSD, Giulio Cavalli Speakers bureau: SOBI, Novartis, Pfizer, Corrado Campochiaro Speakers bureau: Novartis, Pfizer, Roche, GSK, SOBI, Emanuel Della Torre: None declared, Piera Angelillo: None declared, Alessandro Tomelleri: None declared, nicola boffini: None declared, Stefano Tentori: None declared, Francesca Mette: None declared, Patrizia Rovere-Querini: None declared, Annalisa Ruggeri: None declared, Teresa D’Aliberti: None declared, Paolo Scarpelllini: None declared, Giovanni Landoni: None declared, Francesco De Cobelli: None declared, John F. Paolini Shareholder of: Kiniksa, Employee of: Kiniksa, Alberto Zangrillo: None declared, Moreno Tresoldi: None declared, Bruce C. Trapnell Consultant of: Kiniksa, Fabio Ciceri: None declared, Lorenzo Dagna Grant/research support from: Abbvie, BMS, Celgene, Janssen, MSD, Mundipharma Pharmaceuticals, Novartis, Pfizer, Roche, SG, SOBI, Consultant of: Abbvie, Amgen, Biogen, BMS, Celltrion, Novartis, Pfizer, Roche, SG, and SOBI