Tocilizumab in patients with severe COVID-19: a retrospective cohort study
#MMPMID32835257
Guaraldi G
; Meschiari M
; Cozzi-Lepri A
; Milic J
; Tonelli R
; Menozzi M
; Franceschini E
; Cuomo G
; Orlando G
; Borghi V
; Santoro A
; Di Gaetano M
; Puzzolante C
; Carli F
; Bedini A
; Corradi L
; Fantini R
; Castaniere I
; Tabb́ L
; Girardis M
; Tedeschi S
; Giannella M
; Bartoletti M
; Pascale R
; Dolci G
; Brugioni L
; Pietrangelo A
; Cossarizza A
; Pea F
; Clini E
; Salvarani C
; Massari M
; Viale PL
; Mussini C
Lancet Rheumatol
2020[Aug]; 2
(8
): e474-e484
PMID32835257
show ga
BACKGROUND: No therapy is approved for COVID-19 pneumonia. The aim of this study
was to assess the role of tocilizumab in reducing the risk of invasive mechanical
ventilation and death in patients with severe COVID-19 pneumonia who received
standard of care treatment. METHODS: This retrospective, observational cohort
study included adults (?18 years) with severe COVID-19 pneumonia who were
admitted to tertiary care centres in Bologna and Reggio Emilia, Italy, between
Feb 21 and March 24, 2020, and a tertiary care centre in Modena, Italy, between
Feb 21 and April 30, 2020. All patients were treated with the standard of care
(ie, supplemental oxygen, hydroxychloroquine, azithromycin, antiretrovirals, and
low molecular weight heparin), and a non-randomly selected subset of patients
also received tocilizumab. Tocilizumab was given either intravenously at 8 mg/kg
bodyweight (up to a maximum of 800 mg) in two infusions, 12 h apart, or
subcutaneously at 162 mg administered in two simultaneous doses, one in each
thigh (ie, 324 mg in total), when the intravenous formulation was unavailable.
The primary endpoint was a composite of invasive mechanical ventilation or death.
Treatment groups were compared using Kaplan-Meier curves and Cox regression
analysis after adjusting for sex, age, recruiting centre, duration of symptoms,
and baseline Sequential Organ Failure Assessment (SOFA) score. FINDINGS: Of 1351
patients admitted, 544 (40%) had severe COVID-19 pneumonia and were included in
the study. 57 (16%) of 365 patients in the standard care group needed mechanical
ventilation, compared with 33 (18%) of 179 patients treated with tocilizumab
(p=0·41; 16 [18%] of 88 patients treated intravenously and 17 [19%] of 91
patients treated subcutaneously). 73 (20%) patients in the standard care group
died, compared with 13 (7%; p<0·0001) patients treated with tocilizumab (six [7%]
treated intravenously and seven [8%] treated subcutaneously). After adjustment
for sex, age, recruiting centre, duration of symptoms, and SOFA score,
tocilizumab treatment was associated with a reduced risk of invasive mechanical
ventilation or death (adjusted hazard ratio 0·61, 95% CI 0·40-0·92; p=0·020). 24
(13%) of 179 patients treated with tocilizumab were diagnosed with new
infections, versus 14 (4%) of 365 patients treated with standard of care alone
(p<0·0001). INTERPRETATION: Treatment with tocilizumab, whether administered
intravenously or subcutaneously, might reduce the risk of invasive mechanical
ventilation or death in patients with severe COVID-19 pneumonia. FUNDING: None.
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