TY - JOUR
T1 - GM-CSF blockade with mavrilimumab in severe COVID-19 pneumonia and systemic hyperinflammation
T2 - a single-centre, prospective cohort study
AU - De Luca, Giacomo
AU - Cavalli, Giulio
AU - Campochiaro, Corrado
AU - Della-Torre, Emanuel
AU - Angelillo, Piera
AU - Tomelleri, Alessandro
AU - Boffini, Nicola
AU - Tentori, Stefano
AU - Mette, Francesca
AU - Farina, Nicola
AU - Rovere-Querini, Patrizia
AU - Ruggeri, Annalisa
AU - D'Aliberti, Teresa
AU - Scarpellini, Paolo
AU - Landoni, Giovanni
AU - De Cobelli, Francesco
AU - Paolini, John F.
AU - Zangrillo, Alberto
AU - Tresoldi, Moreno
AU - Trapnell, Bruce C.
AU - Ciceri, Fabio
AU - Dagna, Lorenzo
N1 - Funding Information:
GDL and LD conceptualised the study. AZ, MT, FC, and LD supervised the study. GDL, JFP, and LD were involved in preparing the protocol of the study. GDL, GC, CC, ED-T, and LD were involved in the clinical care of the patients. LD was responsible for funding acquisition. GDL, GC, CC, ED-T, PA, AT, NB, ST, FM, NF, PR-Q, AR, TD'A, PS, GL, FDC, and LD were involved in data curation. GDL, GC, JFP, BCT, and LD did formal analysis of data. GDL and LD were responsible for project administration. GDL, GC, and LD prepared the original draft of the manuscript. All authors were involved in writing, reviewing, and editing of the manuscript.
Funding Information:
This expanded access treatment protocol was funded by the San Raffaele Scientific Institute (Milan, Italy). Kiniksa Pharmaceuticals provided the drug and assisted by sharing pre-existing data on mavrilimumab, providing the Pharmacy Manual and the Investigator Brochure available for the ongoing phase 2 trial of mavrilimumab in Giant Cell Arteritis. We thank Kiniksa Pharmaceuticals for providing mavrilimumab and the following Kiniksa team members for their contributions: Fang Fang, Steven Chang, and Ben Hagberg for their advice in data analytics, Dave Nichols and Jeannie Celiberti for coordination of drug supply, Emmanuelle Hugentobler for assistance in manuscript preparation, and Randy Perrin, who facilitated the expanded access treatment protocol. We dedicate this work to the memory of health-care workers who have given their lives in the care of patients with COVID-19.
Publisher Copyright:
© 2020 Elsevier Ltd
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/8
Y1 - 2020/8
N2 - Background: Mortality in patients with COVID-19 pneumonia and systemic hyperinflammation is high. We aimed to examine whether mavrilimumab, an anti-granulocyte–macrophage colony-stimulating factor receptor-α monoclonal antibody, added to standard management, improves clinical outcomes in patients with COVID-19 pneumonia and systemic hyperinflammation. Methods: This single-centre prospective cohort study included patients aged 18 years or older who were admitted to San Raffaele Hospital (Milan, Italy) with severe COVID-19 pneumonia, hypoxia, and systemic hyperinflammation. Patients received a single intravenous dose (6 mg/kg) of mavrilimumab added to standard care given by the hospital at the time. The control group consisted of contemporaneous patients with similar baseline characteristics who received standard care at the same hospital. The main outcome was time to clinical improvement (defined as improvement of two or more points on the seven-point ordinal scale of clinical status). Other outcomes included proportion of patients achieving clinical improvement, survival, mechanical ventilation-free survival, and time to fever resolution. Adverse events were monitored daily. Findings: Between March 17 and April 15, 2020, 13 non-mechanically ventilated patients (median age 57 years [IQR 52–58], 12 [92%] men) received mavrilimumab and 26 patients (median age 60 [IQR 53–67], 17 [65%] men) in the control group received standard care. During the 28-day follow-up, no patients in the mavrilimumab group died, and seven (27%) patients in the control group died (p=0·086). At day 28, all patients in the mavrilimumab group and 17 (65%) patients in the control group showed clinical improvement (p=0·030), with earlier improvement in the mavrilimumab than in the control group (mean time to improvement 8 days [IQR 5 to 11] vs 19 days [11 to >28], p=0·0001). By day 28, one (8%) patient in the mavrilimumab group progressed to mechanical ventilation compared with nine (35%) patients in the control group who progressed to mechanical ventilation or died (p=0·14). By day 14, fever resolved in ten (91%) of 11 febrile patients in the mavrilimumab group, compared with 11 (61%) of 18 febrile patients in the control group (p=0·18); fever resolution was faster in mavrilimumab recipients versus controls (median time to resolution 1 day [IQR 1 to 2] vs 7 days [3 to >14], p=0·0093). Mavrilimumab was well tolerated, with no infusion reactions. Three (12%) patients in the control group developed infectious complications. Interpretation: Mavrilimumab treatment was associated with improved clinical outcomes compared with standard care in non-mechanically ventilated patients with severe COVID-19 pneumonia and systemic hyperinflammation. Treatment was well tolerated. Confirmation of efficacy requires controlled testing. Funding: IRCCS San Raffaele Scientific Institute.
AB - Background: Mortality in patients with COVID-19 pneumonia and systemic hyperinflammation is high. We aimed to examine whether mavrilimumab, an anti-granulocyte–macrophage colony-stimulating factor receptor-α monoclonal antibody, added to standard management, improves clinical outcomes in patients with COVID-19 pneumonia and systemic hyperinflammation. Methods: This single-centre prospective cohort study included patients aged 18 years or older who were admitted to San Raffaele Hospital (Milan, Italy) with severe COVID-19 pneumonia, hypoxia, and systemic hyperinflammation. Patients received a single intravenous dose (6 mg/kg) of mavrilimumab added to standard care given by the hospital at the time. The control group consisted of contemporaneous patients with similar baseline characteristics who received standard care at the same hospital. The main outcome was time to clinical improvement (defined as improvement of two or more points on the seven-point ordinal scale of clinical status). Other outcomes included proportion of patients achieving clinical improvement, survival, mechanical ventilation-free survival, and time to fever resolution. Adverse events were monitored daily. Findings: Between March 17 and April 15, 2020, 13 non-mechanically ventilated patients (median age 57 years [IQR 52–58], 12 [92%] men) received mavrilimumab and 26 patients (median age 60 [IQR 53–67], 17 [65%] men) in the control group received standard care. During the 28-day follow-up, no patients in the mavrilimumab group died, and seven (27%) patients in the control group died (p=0·086). At day 28, all patients in the mavrilimumab group and 17 (65%) patients in the control group showed clinical improvement (p=0·030), with earlier improvement in the mavrilimumab than in the control group (mean time to improvement 8 days [IQR 5 to 11] vs 19 days [11 to >28], p=0·0001). By day 28, one (8%) patient in the mavrilimumab group progressed to mechanical ventilation compared with nine (35%) patients in the control group who progressed to mechanical ventilation or died (p=0·14). By day 14, fever resolved in ten (91%) of 11 febrile patients in the mavrilimumab group, compared with 11 (61%) of 18 febrile patients in the control group (p=0·18); fever resolution was faster in mavrilimumab recipients versus controls (median time to resolution 1 day [IQR 1 to 2] vs 7 days [3 to >14], p=0·0093). Mavrilimumab was well tolerated, with no infusion reactions. Three (12%) patients in the control group developed infectious complications. Interpretation: Mavrilimumab treatment was associated with improved clinical outcomes compared with standard care in non-mechanically ventilated patients with severe COVID-19 pneumonia and systemic hyperinflammation. Treatment was well tolerated. Confirmation of efficacy requires controlled testing. Funding: IRCCS San Raffaele Scientific Institute.
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U2 - 10.1016/S2665-9913(20)30170-3
DO - 10.1016/S2665-9913(20)30170-3
M3 - Article
AN - SCOPUS:85088248861
VL - 2
SP - e465-e473
JO - The Lancet Rheumatology
JF - The Lancet Rheumatology
SN - 2665-9913
IS - 8
ER -