Table 1.
Early Italian observational cohort studies with IL-6 inhibitors in COVID-19.
| PROVED EFFICACY | NO | YES | NO | PARTIAL | YES | YES | NO | YES | PARTIAL | YES |
|---|---|---|---|---|---|---|---|---|---|---|
| Retrospective Cohort Study [Ref.] |
Colaneri et al. (45) |
Capra et al. (46) |
Quartuccio et al. (47) |
Campochiaro et al. (48) |
Gritti et al. (49) |
Guaraldi et al. (50) |
Della Torre et al. (51) |
Rossotti et al. (52) |
Canziani et al. (53) |
Castelnovo et al. (54) |
| STUDY CHARACTERISTICS: | ||||||||||
| Date of publication | May 9, 2020 | May 13, 2020 | May 15, 2020 | May 22, 2020 | Jun 20, 2020 | Jun 24, 2020 | Jul 3, 2020 | Jul 8, 2020 | Jul 8, 2020 | Jan 8, 2021 |
| Period of enrollment (2020) |
Mar 14 - Mar 27 | Feb 26 - Apr 2 | Feb 29 - Apr 6 | ? - Mar 19 | Feb 23 - Apr 9 | Feb 21 - Apr 30 | Mar 14 - Apr 2 | Mar 13 - Apr 3 | Mar 15 - Apr 22 | Mar 6 - May 30 |
| Treatment arm (route, dosage, number of doses) |
Tocilizumab IV 8 mg/kg (x2) |
Tocilizumab IV 400 mg or SC 324 mg (x1) |
Tocilizumab IV 8 mg/Kg (x1) |
Tocilizumab IV 400 mg (x1-2) |
Siltuximab IV 11 mg/kg (x1-2) |
Tocilizumab IV 8 mg/kg (x2) or SC 324 mg (x1) |
Sarilumab IV 400 mg (x1) |
Tocilizumab IV 8 mg/kg (x1-2) |
Tocilizumab IV 8 mg/Kg (x2) |
Tocilizumab IV 8 mg/kg (x2-3) |
| Number of patients recruited |
112 | 85 | 111 | 65 | 60 matched (218 total) |
544 | 56 | 222 | 128 | 112 |
| Number of patients in the treatment arm |
21 | 62 | 42 | 32 | 30 |
179
(88 iv + 91 sc) |
28 | 74 | 64 | 50 |
| PATIENT CHARACTERISTICS (treatment arm): | ||||||||||
| (Median) Age (years old) | 62 | 63 | 62 | 64 | 64 | 64 | 56 | 59 | (mean) 73 | (mean) 61 |
| Male sex (%) | 90.5 | 73 | 79 | 91 | 77 | 71 | 85 | 82 | 63 | 70 |
| (Median) Number of Days from hospitalization |
2 | ≤4 | 2 | 4 | ||||||
| (Median) Number of Days from symptom onset |
≤11 | 11 | 7 | 7 | 13 | |||||
| Hypertension (%) | 38 | 46 | 48 | 37 | 40 | 45 | 21 | 52 | 34 | |
| Type-2 Diabetes (%) | 9.5 | 14 | 12 | 20 | 13 | 11 | 6 | |||
| Heart disease (%) | 9.5 | 14 | 18 | 13 | 12 | 8 | ||||
| Glucocorticoids (%) (Methylprednisolone dose) |
100 (MP 1 mg/Kg) |
0 |
38
(MP 1 mg/Kg) |
0 | 0 | 30 | 0 |
48
(MP 2-3 mg/Kg) |
100
(MP 0.5-1 mg/kg) |
|
| Remdesivir (%) | ≤7 | 9.5 | 0 | 0 | ||||||
| Ambient air (%) | 0 | 0 | 0 | 0 | 0 | |||||
| LFO (%) | 0 | 0 | 0 | 8 | 4 | |||||
| HFO or NIV (%) | 100 | 83 | 100 | 72 | 96 | |||||
| IMV (%) | 62 | 0 | 17 | 18 | 0 | 20 | 0 | |||
| (Median) PaO2/FIO2 ratio (mmHg) | 225 | (≤300) | 107 | 109 | 169 | < 100 in 60% | 180 | (mean) 104 | ||
| (Median) CRP (mg/L) | 21 | 123 | 79 | 156 | 130 | 34-61 (partial data) | 143 | (mean) 198 | ||
| (Median) Ferritin (ng/mL) | 1400 | 1168 (partial data) | 1849 | (mean) 1638 | (mean) 1592 | |||||
| (Median) D-dimer (ng/mL) | 835 | 1000-1210 (partial data) | 1270 | (mean) 3801 | (mean) 2931 | |||||
| (Median) LDH (U/L) | 445 | 625 | 469 | 505.5 | 600-676 (partial data) | 468 | (mean) 524 | |||
| OUTCOMES (treatment vs. standard-of-care): | ||||||||||
| (28-day) Clinical status Improvement (%) |
69 vs. 61
(p=NS) |
17 vs. 18 |
(7-day CPAP)
8 vs. 87 |
|||||||
| (28-day) Discharge (%) | 92 vs. 42 |
(35-day)
24 vs. 100 |
63 vs. 49
(p=NS) |
17 vs. 17 |
(overall)
88 vs. 64.5 |
|||||
| (28-day) IMV (%)
[HR] |
(7-day ICU)
14 vs. 13 |
13 vs. 6
(p=NS) |
[HR 0.615, p=0.072] | (14-day) 18 vs. 16 |
6 vs. 7 |
(30-day)
17 vs. 48 (p=0.001) [HR 0.36, p=0.017] |
||||
| (28-day) IMV or death (%) [HR] |
[Adj HR 0.61, p=0.020]
(For P/F ≤ 150: Adj HR 0.19, p=0.011; significance kept for IV administration only: Adj HR 0.55, p=0.042) |
35 vs.? | ||||||||
|
(28-day) Mortality (%)
[HR] |
(7-day)
24 vs. 21 [OR 0.78, p=NS] |
8 vs. 58
[HR 0.035, p=0.004] |
(35-day)
9.5 vs. 0 |
16 vs. 33
(p=NS) |
(30-day)
33 vs. 53 [HR 0.46, p=0.040] |
(14-day)
7 vs. 20 (p=0.0007) [Adj HR 0.38, p=0.015] (Significance kept for IV administration only: Adj HR 0.29, p=0.048) |
2 vs. 5
(p=NS) |
[HR 0.50, p=0.035] |
(30-day)
27 vs. 38 [HR 0.61, p=NS] |
(overall)
12 vs. 34 |
| Infections (%) | 0 vs. 0 | 65 vs. 0 | 13 vs. 12 (6% one dose vs. 33% two doses, p=0.06) |
43 vs.? |
13 vs. 4
(p<0.0001) |
21 vs. 18 | 32 vs.? | 31 vs. 39 | 0 | |
LEGEND OF COLOURS: Green: numbers falling within the thresholds herein suggested (optimal study and patient characteristics), in relation with statistically significant results and substantial benefit on overall mortality (i.e., positive outcomes). Blue: numbers falling borderline (suboptimal study and patient characteristics), in relation with numerically but not statistically significant results, and substantial benefit on clinical status (e.g., IMV requirement, hospital discharge) (i.e., partially positive outcomes). Red: numbers falling outside of the thresholds (non-optimal study and patient characteristics), in relation with non-significant results, and no substantial benefit on either clinical status or overall mortality (i.e., negative outcomes).
Adj, adjusted; HR, hazard ratio; NS, not significant.