Compassionate use of JAK1/2 inhibitor ruxolitinib for severe COVID-19: a prospective observational study.
Aged
Aged, 80 and over
Biomarkers
COVID-19
/ diagnosis
Combined Modality Therapy
Comorbidity
Compassionate Use Trials
Female
Humans
Janus Kinase 1
/ antagonists & inhibitors
Janus Kinase 2
/ antagonists & inhibitors
Janus Kinase Inhibitors
/ pharmacology
Male
Middle Aged
Nitriles
Prospective Studies
Pyrazoles
/ pharmacology
Pyrimidines
SARS-CoV-2
/ drug effects
Severity of Illness Index
Treatment Outcome
Viral Load
COVID-19 Drug Treatment
Journal
Leukemia
ISSN: 1476-5551
Titre abrégé: Leukemia
Pays: England
ID NLM: 8704895
Informations de publication
Date de publication:
04 2021
04 2021
Historique:
received:
18
06
2020
accepted:
05
08
2020
revised:
24
07
2020
pubmed:
21
8
2020
medline:
23
4
2021
entrez:
21
8
2020
Statut:
ppublish
Résumé
Overwhelming inflammatory reactions contribute to respiratory distress in patients with COVID-19. Ruxolitinib is a JAK1/JAK2 inhibitor with potent anti-inflammatory properties. We report on a prospective, observational study in 34 patients with COVID-19 who received ruxolitinib on a compassionate-use protocol. Patients had severe pulmonary disease defined by pulmonary infiltrates on imaging and an oxygen saturation ≤ 93% in air and/or PaO2/FiO2 ratio ≤ 300 mmHg. Median age was 80.5 years, and 85.3% had ≥ 2 comorbidities. Median exposure time to ruxolitinib was 13 days, median dose intensity was 20 mg/day. Overall survival by day 28 was 94.1%. Cumulative incidence of clinical improvement of ≥2 points in the ordinal scale was 82.4% (95% confidence interval, 71-93). Clinical improvement was not affected by low-flow versus high-flow oxygen support but was less frequent in patients with PaO2/FiO2 < 200 mmHg. The most frequent adverse events were anemia, urinary tract infections, and thrombocytopenia. Improvement of inflammatory cytokine profile and activated lymphocyte subsets was observed at day 14. In this prospective cohort of aged and high-risk comorbidity patients with severe COVID-19, compassionate-use ruxolitinib was safe and was associated with improvement of pulmonary function and discharge home in 85.3%. Controlled clinical trials are necessary to establish efficacy of ruxolitinib in COVID-19.
Identifiants
pubmed: 32814839
doi: 10.1038/s41375-020-01018-y
pii: 10.1038/s41375-020-01018-y
pmc: PMC7437386
doi:
Substances chimiques
Biomarkers
0
Janus Kinase Inhibitors
0
Nitriles
0
Pyrazoles
0
Pyrimidines
0
ruxolitinib
82S8X8XX8H
JAK1 protein, human
EC 2.7.10.2
JAK2 protein, human
EC 2.7.10.2
Janus Kinase 1
EC 2.7.10.2
Janus Kinase 2
EC 2.7.10.2
Types de publication
Clinical Trial
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1121-1133Investigateurs
Francesco Mannelli
(F)
Giacomo Coltro
(G)
Duccio Fantoni
(D)
Miriam Borella
(M)
Enrica Ravenda
(E)
Benedetta Peruzzi
(B)
Roberto Caporale
(R)
Lorenzo Cosmi
(L)
Francesco Liotta
(F)
Letizia Lombardelli
(L)
Federica Logiodice
(F)
Anna Vanni
(A)
Lorenzo Salvati
(L)
Chiara Lazzeri
(C)
Manuela Bonizzoli
(M)
Adriano Peris
(A)
Giovanni Cianchi
(G)
Alberto Bosi
(A)
Michela Pucatti
(M)
Paolo Fontanari
(P)
Silvia Benemei
(S)
Marco Matucci Cerinic
(M)
Lucia Turco
(L)
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