Table 3.
Safety of immunomodulatory drugs assessed by randomised controlled trials in moderate-to-severe COVID-19 (with oxygen therapy) and in critical COVID-19 (patients in ICU)
| Drug | Author, year | Study groups | Results | RoB |
| Hydroxychloroquine | Cavalcanti et al 202016 | SOC+PBO SOC+HCQ+AZT |
Prolongation of the corrected QT interval (p=0.04 for HCQ+AZT; p=0.01 for HCQ) and elevation of liver enzyme p=0.02. More SAE and two deaths in HCQ+AZT groups. |
Unclear |
| RECOVERY 202018 | SOC SOC+HCQ |
HCQ group: greater risk of death from cardiac causes (mean (±SE) excess, 0.4±0.2 percentage points) and from non–SARS-CoV-2 infection (mean excess, 0.4±0.2 percentage points). | Unclear | |
| Tang et al 202015 | SOC SOC+HCQ |
21 (30%) patients HCQ vs 7 (9%) patients PBO. | High | |
| Huang et al 202014 | SOC+HCQ SOC |
5 patients, 9 AEs in HCQ group, none in control group. | High | |
| Self et al 202020 | SOC+HCQ SOC |
30 SAEs were reported, including 18 SAEs from 14 patients (5.8%) in the HCQ group and 12 serious adverse events from 11 patients (4.6%) in the control group. | Unclear | |
| Ulrich et al 202021 | SOC+HCQ SOC |
No difference in AEs between the groups. HCQ was associated with a slight increase in mean corrected QT interval, an increased D-dimer, and a trend towards an increased length of stay. | High | |
| Corticosteroids | Jeronimo et al 20207 | SOC+MTP SOC+PBO |
More insulin at day 7 needed in the MTP group. No more sepsis (but antibiotics in the SOC regimen). |
Unclear |
| Tomazini et al 20208 | SOC+DEX SOC |
No difference in AEs between groups. | High | |
| Dequin et al 202010 | SOC+HCT SOC+PBO |
The proportions of bacteraemia were 6.6% in the hydrocortisone group and 11.0% in the placebo group. | Unclear | |
| Edalatifard et al 202011 | SOC+MTP SOC |
2 patients in each group (5.8% and 7.1%) showed SAE. | High | |
| Angus et al 20209 | SOC+HCT SOC |
10 patients (2.6%) with SAE, 9 of whom were in the fixed-dose (n=4) and shock-dependent (n=5) HCT groups. Two events (severe neuromyopathy and fungaemia) occurred in the fixed-dose hydrocortisone group. | Unclear | |
| Convalescent plasma | Simonovich et al 202043 | SOC+convalescent plasma SOC+PBO |
No difference in AEs between groups. | Unclear |
| Li et al 202041 | SOC+convalescent plasma SOC | No difference in AEs between groups. | High | |
| Agarwal et al 202042 | SOC+convalescent plasma. SOC | No difference in AEs between groups. | High | |
| Tocilizumab | Stone et al 202024 | SOC+TCZ SOC+PBO |
Neutropaenia developed in 22 patients in the TCZ group, as compared with only one patient in the placebo group (p=0.002), but serious infections occurred in fewer patients in the TCZ group (13 (8.1%) vs 14 (17.3%); p=0.03). | Unclear |
| Hermine et al 2020 CORIMUNO-1923 | SOC+TCZ SOC |
SAE occurred in 20 (32%) patients in the TCZ group and 29 (43%) in the SOC group (p = 0.21). Serious infections occurred in 2 (3%) patients in the TCZ group and 14 (21%) in the control group. Neutropaenia developed in 4 (6%) in the TCZ group and 0 in the control group. | Unclear | |
| Colchicine | Deftereos et al 202038 | SOC+COL SOC |
Diarrhoea was more frequent in the colchicine group (25 patients(45.5%) versus nine patients (18.0%); p = 0.003). | Unclear |
| Ruxolitinib | Cao et al 202036 | SOC+RUXO SOC |
No differences between groups 15 patients (71.4%) PBO group and 16 (80%) in RUXO group. | High |
| Interferon beta | Davoudi-Monfared et al 2020, Rahmani et al 202033 34 | SOC+IFN beta SOC | No differences between groups (all p>0.05). A total of 47 common AEs in the IFN and 62 in the control group. | High |
| Monk et al 202035 | SOC+IFN beta PBO+SOC | Treatment emergent AEs were more common in the IFN group. | Unclear | |
| Vilobelimab | Vlaar et al 37 | SOC+VIL SOC | Numbers of SAE were similar between groups (60% of patients in the IFX-1 group vs 47% in the control group). | Unclear |
| Baricitinib | Kalil et al 202031 | BARI+RDV+ SOC PBO+RDV+SOC | No difference in AEs between groups. | Unclear |
Only studies reporting on safety are shown.
AE, adverse event; AZT, azithromycin; COL, colchicine; DEX, dexamethasone; HCQ, hydroxychloroquine; HCT, hydrocortisone; IFN, interferon; MTP, methylprednisolone; MV, mechanical ventilation; PBO, placebo; RR, relative risk; RUXO, ruxolitinib; SAE, severe adverse event; SE, standard error; SOC, standard of care; TCZ, tocilizumab; VIL, vilobelimab.