Treatment-related adverse events
| Author, year | Therapy | Adverse effects |
| Balkhair et al, 202026 | Anakinra | Treatment: infection (11%), ALT rise (14%). Control: infection (18%), ALT rise (9%) |
| Huet et al, 202029 | Anakinra | Treatment: ALT rise (13%). Control: 9% in anakinra |
| Kooistra et al, 202035 | Anakinra | Treatment: secondary infection (33%). Control: secondary infection (23%) |
| *Kyriazopoulou et al, 202028 | Anakinra | Increased leucopenia in treatment group versus controls (8.5% vs 2.3%; p=0.05) |
| Cauchois et al, 202024 | Anakinra | N/R |
| Cavalli et al, 202025 | Anakinra | Treatment: Staphylococcus epidermis (14%), deranged liver enzymes (10%). Control: bacteraemia (13%), deranged liver enzymes (31%) |
| Narain et al, 202027 | Anakinra | N/R |
| Benucci et al, 202044 | Sarilumab | Nil |
| Della-Torre et al, 202030 | Sarilumab | Treatment: infections (21%), neutropenia (14%), liver enzyme increase (14%), thromboembolism (7%). Control: infections (18%), thromboembolism (7%) |
| *Gordon et al, 202120 | Sarilumab | No serious event in sarilumab group and 11 events in control |
| Gremese et al, 202051 | Sarilumab | Neutropenia (15%), elevated liver enzymes (11%) |
| Sinha et al, 202054 | Sarilumab or tocilizumab | Bacterial infection (13%) |
| *Gritti et al, 202031 | Siltuximab | Nil |
| Albertini et al, 202059 | Tocilizumab | Elevated liver enzymes (64%) |
| Antony et al, 202062 | Tocilizumab | N/R |
| Campins et al, 202065 | Tocilizumab | Nil |
| *Carvalho et al, 202068 | Tocilizumab | Nil |
| Chilimuri et al, 202055 | Tocilizumab | N/R |
| Dastan et al, 202071 | Tocilizumab | Transient diplopia (4.8%), Bell’s palsy (2.4%) |
| *Gordon et al, 202120 | Tocilizumab | 9 serious adverse events in tocilizumab group and 11 events in control |
| Hermine et al, 202023 | Tocilizumab | Treatment: serious adverse events occurred in 20 (32%). Control: 29 (43%) (p=0.21) |
| Lewis et al, 202037 | Tocilizumab | Increased infection rate in treatment group (aOR 4.18; 95% CI 2.72 to 6.52) |
| Malekzadeh et al, 202078 | Tocilizumab | Nil |
| Mikulska et al, 202081 | Tocilizumab | N/R |
| Morena et al, 202084 | Tocilizumab | Elevated liver enzymes (29%), thrombocytopenia (14%), neutropenia (6%), infections (24%) |
| Nasa et al, 202041 | Tocilizumab | Two patients (9.1%) developed deranged LFTs and two patients (9.1%) developed secondary sepsis |
| Perrone et al, 202087 | Tocilizumab | Allergic reactions (0.4%), deranged liver enzymes (10.5%) |
| *Petrak et al, 202046 | Tocilizumab | N/R |
| *Rosas et al, 202086 | Tocilizumab | 66 serious infections (21%) were reported in the treatment arm and 49 (25.9%) in the placebo arm. Adverse events similar in both arms |
| Roumier et al, 202032 | Tocilizumab | Treatment: higher rates of neutropenia (35% vs 0%, p<0.001). Control: trend towards increased bacterial infections (22% vs 38%, p=0.089; including ventilator-acquired pneumonia: 8% vs 26%, p=0.022) and shorter time to infection (mean 18 vs 10 days, p=0.029) |
| Salama et al, 202022 | Tocilizumab | Serious adverse events occurred in 38 of 250 patients (15.2%) in the tocilizumab group and 25 of 127 patients (19.7%) in the placebo group |
| Salvarani et al, 202036 | Tocilizumab | Nil |
| *Sanchez-Montalva et al, 202038 | Tocilizumab | Nil |
| Sciascia et al, 202040 | Tocilizumab | Nil |
| Stone et al, 202021 | Tocilizumab | Neutropenia developed in 22 patients in the treatment group, as compared with only 1 patient in the placebo group (p=0.002), but serious infections occurred in fewer patients in the tocilizumab group (13 (8.1%)vs 14 (17.3%); p=0.03) |
| Strohbehn et al, 202042 | Tocilizumab | Treatment: bacterial infections (15.6%). Control: not reported |
| Toniati et al, 202045 | Tocilizumab | Septic shock (2%), gastrointestinal perforation (1%) |
| Biran et al, 202047 | Tocilizumab | Treatment: secondary bacterial infection in 17%. Control: secondary bacterial infection in 13% |
| Canziani et al, 202049 | Tocilizumab | HR 0.71 (95% CI 0.38 to 1.32) for infection, HR 0.89 (95% CI 0.39 to 2.06) for thrombosis, HR 1.17 (95% CI 0.47 to 2.92) for bleeding |
| Capra et al, 202052 | Tocilizumab | Nil |
| De Rossi et al, 202057 | Tocilizumab | Significant rise (from 44.3±28.3 to 103±141.3) in ALT in patients taking intravenous dose |
| Eimer et al, 202060 | Tocilizumab | Blood stream infection: 4 (18%) in treatment group versus 6 (27%) in control |
| Fisher et al, 202063 | Tocilizumab | No increased risk of secondary infection (OR 1.17; 95% CI 0.51 to 2.71) |
| Galván-Román et al, 202066 | Tocilizumab | N/R |
| *Moreno Garcia et al, 202069 | Tocilizumab | N/R |
| Gokhale et al,202072 | Tocilizumab | N/R |
| Guaraldi et al, 202074 | Tocilizumab | 13% treated diagnosed with new infections versus 4% in control (p<0.0001) |
| Guisado-Vasco et al, 202076 | Tocilizumab | N/R |
| Gupta et al, 202079 | Tocilizumab | Treated and control patients experienced the following adverse events: secondary infection (140 (32.3%)vs 1085 (31.1%)), AST or ALT level elevation of more than 250 U/L (72 (16.6%)vs 452 (12.9%)) |
| Hill et al, 202082 | Tocilizumab | In treatment group compared with control group, there was increased sepsis (21%vs16%), ALT rise (9% vs 4%) and thrombocytopenia (12% vs 4%) |
| Holt et al, 202085 | Tocilizumab | N/R |
| Ip et al, 202088 | Tocilizumab | N/R |
| Kewan et al, 202090 | Tocilizumab | Similar rates of hospital-acquired infections occurred in both cohorts (18% in treatment and 22% in control) |
| Kimmig et al, 202033 | Tocilizumab | Treatment associated with increased secondary bacterial (aOR 2.76; 95% CI 1.11 to 7.2) and fungal (5.6% vs 0%, p=0.112) infections |
| Klopfenstein et al, 202034 | Tocilizumab | N/R |
| Martinez-Sanz et al, 202039 | Tocilizumab | N/R |
| Narain et al, 202027 | Tocilizumab | N/R |
| Patel et al, 202043 | Tocilizumab | N/R |
| Pettit et al, 202048 | Tocilizumab | Overall infection rate was similar (16.2% treatment vs 17.5% control), but late onset infections occurred in more treated patients (23% vs 8%; p=0.013). In treated, 26% experienced an increase to >5 times upper limit normal of LFTs |
| Potere et al, 202050 | Tocilizumab | Nil |
| *Ramaswamy et al, 202053 | Tocilizumab | N/R |
| Rodríguez-Baño et al, 202056 | Tocilizumab | Secondary bacterial infection similar in both groups (treated 12.5% vs 10.3% control; p=0.57) |
| Rojas-Marte et al, 202058 | Tocilizumab | Bacteraemia was more common in the control group (24% vs 13%, p=0.43), while fungemia was similar for both (3% vs 4%, p=0.72) |
| Roomi et al, 202061 | Tocilizumab | N/R |
| Rosas et al, 202064 | Tocilizumab | Nil |
| Rossi et al, 202067 | Tocilizumab | N/R |
| Rossotti et al, 202070 | Tocilizumab | Infectious complication in 32.4% |
| Ruiz-Antorán et al, 202073 | Tocilizumab | 32.6% in treated versus 30.3% in control had increase in liver enzymes. Bacteraemia in one patient (0.4%) |
| Somers et al, 202075 | Tocilizumab | Higher rate of superinfection in treated group (54% vs 26%; p<0.001) |
| Tian et al, 202077 | Tocilizumab | Deranged LFTs in 14% of tocilizumab and 14% of control group |
| Tsai et al, 202080 | Tocilizumab | N/R |
| *Wadud et al, 202083 | Tocilizumab | N/R |
| Zheng et al, 202086 | Tocilizumab | N/R |
Adverse events for drug under study reported. Adverse events for control population reported where applicable.
*Non-peer-reviewed preprint study.
ALT, alanine transaminase; aOR, adjusted odds ratio; AST, aspartate transaminase; LFTs, liver function tests; N/R, not reported.