Outcomes and biomarker analyses among patients with COVID-19 treated with interleukin 6 (IL-6) receptor antagonist sarilumab at a single institution in Italy.
Aged
Antibodies, Monoclonal, Humanized
/ therapeutic use
Antiviral Agents
/ therapeutic use
Biomarkers, Pharmacological
/ blood
COVID-19
Coronavirus Infections
/ complications
Female
Humans
Interleukin-6
/ blood
Italy
Lymphocyte Count
Male
Middle Aged
Neutrophils
Pandemics
Pneumonia, Viral
/ complications
Receptors, Interleukin-6
/ antagonists & inhibitors
Retrospective Studies
Treatment Outcome
COVID-19 Drug Treatment
case reports
immunomodulation
inflammation mediators
Journal
Journal for immunotherapy of cancer
ISSN: 2051-1426
Titre abrégé: J Immunother Cancer
Pays: England
ID NLM: 101620585
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
accepted:
17
07
2020
entrez:
14
8
2020
pubmed:
14
8
2020
medline:
4
9
2020
Statut:
ppublish
Résumé
The inflammatory pathology observed in severe COVID-19 disease caused by the 2019 novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is characterized by elevated serum levels of C reactive protein (CRP) and cytokines, including interferon gamma, interleukin 8 (IL-8), and interleukin 6 (IL-6). Initial reports from the outbreak in Italy, China and the USA have provided anecdotal evidence of improved outcomes with the administration of anti-IL-6 agents, and large-scale trials evaluating these therapies are ongoing. In this retrospective case series, clinical outcomes and correlates of response to treatment with the IL-6 receptor antagonist sarilumab are described for 15 patients with COVID-19 from a single institution in Southern Italy. Among 10 patients whose symptoms improved after sarilumab treatment, rapid decreases in CRP levels corresponded with clinical improvement. Lower levels of IL-6 at baseline as well as lower neutrophil to lymphocyte ratio as compared with patients whose COVID-19 did not improve with treatment were associated with sarilumab-responsive disease. This observation may reflect a possible clinical benefit regarding early intervention with IL-6-modulatory therapies for COVID-19 and that CRP could be a potential biomarker of response to treatment.
Sections du résumé
BACKGROUND
The inflammatory pathology observed in severe COVID-19 disease caused by the 2019 novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is characterized by elevated serum levels of C reactive protein (CRP) and cytokines, including interferon gamma, interleukin 8 (IL-8), and interleukin 6 (IL-6). Initial reports from the outbreak in Italy, China and the USA have provided anecdotal evidence of improved outcomes with the administration of anti-IL-6 agents, and large-scale trials evaluating these therapies are ongoing.
STUDY DESCRIPTION
In this retrospective case series, clinical outcomes and correlates of response to treatment with the IL-6 receptor antagonist sarilumab are described for 15 patients with COVID-19 from a single institution in Southern Italy. Among 10 patients whose symptoms improved after sarilumab treatment, rapid decreases in CRP levels corresponded with clinical improvement. Lower levels of IL-6 at baseline as well as lower neutrophil to lymphocyte ratio as compared with patients whose COVID-19 did not improve with treatment were associated with sarilumab-responsive disease.
CONCLUSIONS
This observation may reflect a possible clinical benefit regarding early intervention with IL-6-modulatory therapies for COVID-19 and that CRP could be a potential biomarker of response to treatment.
Identifiants
pubmed: 32784217
pii: jitc-2020-001089
doi: 10.1136/jitc-2020-001089
pmc: PMC7418768
pii:
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Antiviral Agents
0
Biomarkers, Pharmacological
0
IL6 protein, human
0
IL6R protein, human
0
Interleukin-6
0
Receptors, Interleukin-6
0
sarilumab
NU90V55F8I
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Commentaires et corrections
Type : ErratumIn
Informations de copyright
© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Déclaration de conflit d'intérêts
Competing interests: AMG: advisory and consultant role for BMS, MSD and Novartis; and travel grants from BMS, Merck Serono, Pierre Fabre, Roche and Novartis. PAA: consultant/advisory role for Bristol-Myers Squibb, Roche-Genentech, Merck Sharp & Dohme, Array, Novartis, Merck Serono, Pierre Fabre, Incyte, NewLink Genetics, Genmab, MedImmune, AstraZeneca, Syndax, SunPharma, Sanofi, Idera, Ultimovacs, Sandoz, Immunocore, 4SC, Alkermes, Italfarmaco, and Nektar; research funds from Bristol-Myers Squibb, Roche-Genentech, and Array; and travel support from MSD.
Références
N Engl J Med. 2020 May 7;382(19):1787-1799
pubmed: 32187464
J Infect. 2020 Jul;81(1):e6-e12
pubmed: 32283162
Lancet Respir Med. 2020 Apr;8(4):420-422
pubmed: 32085846
Cold Spring Harb Perspect Biol. 2014 Sep 04;6(10):a016295
pubmed: 25190079
Cancer Discov. 2016 Jun;6(6):664-79
pubmed: 27076371
Int Immunopharmacol. 2020 Jul;84:106504
pubmed: 32304994
J Allergy Clin Immunol. 2020 Aug;146(2):325-327
pubmed: 32479759
Oncology. 2020;98(3):131-137
pubmed: 31958792
QJM. 2020 Jul 1;113(7):474-481
pubmed: 32181807
J Clin Invest. 2020 May 1;130(5):2620-2629
pubmed: 32217835
Clin Rev Allergy Immunol. 2016 Apr;50(2):140-58
pubmed: 26797962
J Immunother Cancer. 2020 May;8(1):
pubmed: 32385146
Clin Infect Dis. 2020 Jul 28;71(15):769-777
pubmed: 32176772
Cytokine. 2018 Apr;104:8-13
pubmed: 29414327
J Thromb Haemost. 2020 Jun;18(6):1324-1329
pubmed: 32306492
JAMA. 2020 Apr 6;:
pubmed: 32250385
Expert Rev Clin Immunol. 2019 Aug;15(8):813-822
pubmed: 31219357
Am J Hematol. 2020 Jul;95(7):834-847
pubmed: 32282949
N Engl J Med. 2020 Apr 30;382(18):e41
pubmed: 32212516
J Allergy Clin Immunol. 2020 Jul;146(1):1-7
pubmed: 32344056
Travel Med Infect Dis. 2020 Mar - Apr;34:101623
pubmed: 32179124
Am Soc Clin Oncol Educ Book. 2019 Jan;39:433-444
pubmed: 31099694
Lancet Infect Dis. 2020 Apr;20(4):425-434
pubmed: 32105637
Intensive Care Med. 2020 May;46(5):846-848
pubmed: 32125452
Lancet Rheumatol. 2020 Aug;2(8):e474-e484
pubmed: 32835257
Obesity (Silver Spring). 2020 Jul;28(7):1200-1204
pubmed: 32352637
Cancer. 2016 Sep 15;122(18):2857-66
pubmed: 27244347
JAMA. 2020 Mar 17;:
pubmed: 32181795
Ann Intern Med. 2020 May 5;172(9):629-632
pubmed: 32163542
N Engl J Med. 2020 Mar 26;382(13):1268-1269
pubmed: 32109011
Hematology Am Soc Hematol Educ Program. 2015;2015:190-6
pubmed: 26637720
Lancet Respir Med. 2020 Apr;8(4):e20
pubmed: 32171067
J Clin Invest. 2020 May 1;130(5):2202-2205
pubmed: 32217834
J Biol Regul Homeost Agents. 2020 Mar 14;34(2):327-331
pubmed: 32171193
Lancet Rheumatol. 2020 Jul;2(7):e393-e400
pubmed: 32835245
Clin Immunol. 2020 Jun;215:108448
pubmed: 32353634
JAMA. 2020 Apr 22;:
pubmed: 32320003
J Microbiol Immunol Infect. 2020 Jun;53(3):368-370
pubmed: 32205092
Lancet. 2020 May 22;:
pubmed: 32450107
Nat Immunol. 2015 May;16(5):448-57
pubmed: 25898198
Microbiol Mol Biol Rev. 2012 Mar;76(1):16-32
pubmed: 22390970
Emerg Infect Dis. 2020 Aug;26(8):1941-1943
pubmed: 32348233
Proc Natl Acad Sci U S A. 2020 May 19;117(20):10970-10975
pubmed: 32350134
J Immunol Methods. 2016 Jul;434:1-8
pubmed: 27049586
Obesity (Silver Spring). 2020 Jul;28(7):1195-1199
pubmed: 32271993
Clin Infect Dis. 2020 Mar 16;:
pubmed: 32173725
J Microbiol Immunol Infect. 2020 Jun;53(3):404-412
pubmed: 32173241
Hematol Oncol. 2019 Jun;37 Suppl 1:48-52
pubmed: 31187535
J Thorac Oncol. 2020 May;15(5):700-704
pubmed: 32114094
Cytokine. 2005 Feb 21;29(4):169-75
pubmed: 15652449
Clin Infect Dis. 2001 Jan;32(1):76-102
pubmed: 11118387
N Engl J Med. 2020 Jul 17;:
pubmed: 32678530
Blood. 2016 Jun 30;127(26):3321-30
pubmed: 27207799
Nat Rev Immunol. 2020 Jun;20(6):363-374
pubmed: 32346093
Am J Respir Crit Care Med. 2020 Jun 1;201(11):1372-1379
pubmed: 32242738
Clin Immunol. 2020 May;214:108393
pubmed: 32222466
Front Public Health. 2020 Apr 29;8:152
pubmed: 32411652