Head-to-head comparisons of immunomodulators for the treatment of COVID-19 are lacking. |
We aim to rank immunomodulators in the treatment of COVID-19 according to their efficacy and safety. |
Regarding both efficacy and safety, ruxolitinib was the best treatment followed by baricitinib. Meanwhile, methylprednisolone had the worst combined efficacy and safety among the examined treatments. |
Further well-conducted randomized controlled trials should focus on JAK inhibitors. Methylprednisolone use should be discouraged because of its poor efficacy and high risk of superimposed infection. |
Introduction
Methods
Search Strategies
Selection of Studies
Inclusion Criteria
Data Extraction
Outcome of Interest
Transitivity Assessment Across Treatment Comparisons
Quality Assessment
Statistical Analysis
Results
Study Characteristics and Included Studies
Study | N | Intervention | Timing of interventionb (days) | Comparator | Severityc | Durations of treatment | Outcomes | Country |
---|---|---|---|---|---|---|---|---|
Corticosteroids vs. SOC (n = 11) | ||||||||
P. Horby [6], 2021 (Recovery) | 6425 | DEX (6 mg/day) | 8.0 (5.0–13.0) | SOC | Mixed | Up to 10 days | Mortality rate, IMV, infection | UK Indonesia, Nepal |
H. Jamaati [35], 2021 | 50 | DEX (10–20 mg/day)e | N/A | SOC | Mild to moderate | 10 days | Mortality rate IMV | Iran |
B. M. Tomazini [36], 2020 (CoDEX) | 299 | DEX (10–20 mg/day)e | 9.0 (7.0–11.0) | SOC | Moderate to severe | > 5 days | Mortality rate IMV, infection | Brazil |
J. Villar [37], 2020 (Dexa-COVID19 network) | 200 | DEX (10–20 mg/day)e | N/A | SOC | Moderate to severe | 10 days | Mortality rateh | Spain |
D. C. Angus [38], 2020 (The REMAP-CAP COVID-19) | 384 | HYD | 1.2 (0.8–2.6)i Since hospital admission | SOC | Severe | A fixed dose: 50–100 mg q 6 h for 7 days A shock-dependent dose: 50 mg q 6 h up to 28 days | Mortality rate, infection | Multinational |
P. F. Dequin [39], 2020 (CAPE COVID trial group) | 149 | HYD (50–200 mg/day)f | 9.0 (7.0–11.5) | SOC | Critically ill | 8–14 days | Mortality rate IMV, infection | France |
M. W. Petersen [40], 2020 (COVID STEROID) | 30 | HYD (200 mg/day) | 4.0 (1.0–7.0) Since hospital admission | SOC | Severe | 7 days | Mortality rate | Denmark, Sweden, Switzerland, India |
L. Corral-Gudino [41], 2021 (Glucocovid) | 64 | MET | 12.0 ± 5.0 | SOC | Moderate to severe | 80 mg/day for 3 days followed by 40 mg/day for 3 days | Mortality rate IMV, infection | Spain |
M. Edalatifard [42], 2020 | 72 | MET (250 mg/day) | 24–48 h after hospitalization | SOC | Severe | 3 days | Mortality rate, infection | Iran |
C. M. P. Jeronimo [24], 2020 (COVID-19; Metcovid) | 393 | MET (1 MKD) | 13.0 (9.0–16.0) | SOC | Moderate to severe | 5 days | Mortality rate, IMV, infection | Brazil |
X. Tang [43], 2021 | 86 | MET (1 MKD) | 8.0 (6.0–13.0) | SOC | Mixed | 7 days | Mortality rate, infection | China |
IL receptor antagonists vs. SOC (n = 10) | ||||||||
RECOVERY [29], 2021 | 4116 | TOC (8 MKD) 1–2 dose | 9.0 (7.0–13.0) | SOC | Mixed | A second dose 12–24 h after first dose | Mortality, IMV, infection | UK |
O. Hermine [44], 2021 (CORIMUNO-TOCI) | 130 | TOC (8 MKD) | 10.0 (7.0–13.0) | SOC | Moderate to severe | Days 1, 3 | Mortality IMV, infection | France |
O. Rosas [45], 2021 (COVACTA) | 438 | TOC (8 MKD) 1–2 dose | 11.0 (1.0–49.0) | SOC | Severe | A second dose 8–24 h after first dose | Mortality, IMV, infection | Multinational |
C. Salama [46], 2021 (EMPACTA) | 377 | N/A | SOC | Mixed | Mortality, IMV, infection | Multinational | ||
C. Salvarani [47], 2021 (RCT-TCZ-COVID-19) | 126 | TOC (8 MKD) 2 doses | 7.0 (4.0–11.0) | SOC | Mildd | 12 h apart | Mortality, infection | Italy |
A.S. Soin [48], 2021 (COVINTOC) | 179 | TOC (6 MKD) 1–2 dose | N/A | SOC | Moderate to severe | A second dose 12 h to 7 days after first dose | Mortality IMV, infection | India |
J. H. Stone [49], 2020 (BACC bay) | 242 | TOC (8 MKD) Single dose | 9.0 (6.0–13.0) | SOC | Mixed | Day 1 | Mortality, IMV, infection | USA |
V. C. Veiga [50], 2021 | 129 | TOC (8 MKD) Single dose | 10.0 ± 3.1 | SOC | Severe to critical | Day 1 | Mortality, IMV, infection | Brazil |
F. X. Lescure [26], 2021 | 416 | SAR (200–400 mg daily) 1–2 dose A second dose 8–24 h after first dose | SAR 200 mg 5.0 (2.0–10.0) SAR 400 mg 4.0 (2.0–9.0) | SOC | Severe to critical | A second dose 8–24 h after first dose | Time to clinical improvement, mortality, infection | Multinational |
CORIMUNO-19 collaborative group [51], 2021 | 114 | ANAg | 10.0 (8.0–13.0) | SOC | Mild to moderate | 5 days | IMV, mortality, infection | France |
JAK inhibitors vs. placebo (n = 3) | ||||||||
Y. Cao [52], 2020 | 41 | RUX (5 mg twice a day) | N/A | SOC | Severe | Until treatment failure, toxicity, or death | Time to clinical improvement, mortality, IMV, infection | China |
A. C. Kalil [53], 2021 | 1033 | BAR (4 mg/day) (2 mg/day if GFR < 60) | 8.0 (5.0–10.0) | SOC | Moderate to severe | ≤ 14 days | Mortality, time to recovery, IMV, infection | Multinational |
P.O. Guimaraes [54], 2021 (STOP-COVID) | 289 | TOF (10 mg twice daily) | 10.0 (7.0–12.0) | SOC | Mixed | For up to 14 days | Mortality, infection | Brazil |
Others (n = 2) | ||||||||
A.C. Gordon [22], 2021 REMAP-CAP | 865 | TOC (8 mg/kg) 1–2 dose or SAR (400 mg/day) single dose | TOC 1.2 (0.8–2.8) SAR 1.4 (0.9–2.8) Since hospital admission | SOC | Critically ill | TOC A second dose 12–24 h after first dose SAR Day 1 | Mortality, IMV | UK |
K. Ranjbar [23], 2021 | 86 | MET (2 mg/kg) | N/A | DEX (6 mg/day) 10 days | Severe | 10 days | Mortality, IMV | Iran |