TABLE 2.
Primary and secondary outcomes
| Outcome | TOCI-2 trial | SARI-2 trial | ||||
| Tocilizumab (n=49) | Usual care (n=43) | Treatment effect | Sarilumab (n=48) | Usual care (n=33) | Treatment effect | |
| Primary outcomes | ||||||
| No improvement in WHO-CPS score at day 4 (n (%)) | 35 (71) | 30 (70) | 1.7% (−13.6–17.1%)¶ | 34 (71) | 26 (79) | −7.3% (−22.5–8.7%)¶ |
| Posterior probability of any benefit | 49.2% | 77.7% | ||||
| Posterior probability of moderate or greater benefit | 22.0% | 57.5% | ||||
| Extubation or removal of NIV# >48 h at day 14 (%) | 47 (32–60) | 42 (27–56) | HR 1.19 (0.71–2.04)+ | 38 (24–51) | 33 (18–50) | HR 1.05 (0.55–2.07)+ |
| Posterior probability of any benefit | 71.4% | 54.9% | ||||
| Posterior probability of moderate or greater benefit | 51.9% | 38.9% | ||||
| Secondary outcomes | ||||||
| Overall survival (%) | ||||||
| Estimate at day 14 | 90 (82–99) | 79 (68–92) | HR 0.37 (0.12–1.15) | 75 (64–88) | 73 (59–90) | HR 0.95 (0.40–2.25) |
| Estimate at day 28 | 84 (74–95) | 77 (65–90) | HR 0.56 (0.22–1.46) | 71 (59–85) | 67 (52–85) | HR 0.89 (0.40–1.96) |
| Estimate at day 90 | 76 (64–89) | 70 (57–85) | HR 0.67 (0.30–1.49) | 71 (59–85) | 61 (46–80) | HR 0.74 (0.35–1.58) |
| WHO-CPS score (0–10) | ||||||
| Median (IQR) at day 4 | 7 (7–8) | 8 (7–8) | OR 0.85 (0.39–1.82)§ | 7 (7–8) | 8 (7–8) | OR 0.88 (0.38–2.02)§ |
| Median (IQR) at day 7 | 7 (5–8) | 8 (7–8) | OR 0.69 (0.32–1.47)§ | 8 (7–8) | 8 (7–8) | OR 1.07 (0.47–2.40)§ |
| Median (IQR) at day 14 | 7 (5–8) | 7 (5–9) | OR 0.68 (0.32–1.43)§ | 7 (5–10) | 7 (5–10) | OR 1.13 (0.50–2.57)§ |
| Day 2 to day 14 longitudinal analysis | OR 0.76 (0.27–2.13)ƒ | OR 0.72 (0.21–2.41)ƒ | ||||
| Day 28 ventilator-free days (mean±sd) | 12.8±10.7 | 10.3±11.1 | MD −2.5 (−6.9–1.7) | 10.3±11.1 | 8.7±11.0 | MD −1.5 (−6.1–3.9) |
| Patients with WHO-CPS ≥7 (mean±sd) | 9.8±9.5 | 7.2±9.4 | MD −2.5 (−6.6–2.7) | 7.5±9.5 | 4.6±7.6 | MD −2.9 (−7.4–1.7) |
| Oxygen supply independency (%) | ||||||
| Estimate at day 28 | 59 (44–72) | 49 (33–63) | HR 1.44 (0.82–2.52) | 44 (29–57) | 36 (20–53) | HR 1.20 (0.59–2.44) |
| Estimate at day 90 | 69 (53–80) | 64 (47–77) | HR 1.28 (0.80–2.03) | 71 (52–83) | 56 (35–72) | HR 1.29 (0.74–2.25) |
| Discharge (%) | ||||||
| Estimate at day 28 | 55 (40–68) | 42 (27–56) | HR 1.45 (0.80–2.63) | 35 (22–49) | 30 (16–46) | HR 1.21 (0.55–2.66) |
| Estimate at day 90 | 70 (54–82) | 60 (44–74) | HR 1.35 (0.84–2.17) | 65 (48–77) | 52 (33–68) | HR 1.30 (0.71–2.37) |
| ICU discharge (%)++ | ||||||
| Estimate at day 28 | 72 (55–84) | 60 (42–74) | HR 1.28 (0.73–2.24) | 60 (43–74) | 71 (50–85) | HR 0.78 (0.42–1.44) |
| Estimate at day 90 | 84 (66–93) | 83 (63–93) | HR 1.15 (0.73–1.81) | 79 (61–89) | 82 (57–93) | HR 0.84 (0.49–1.47) |
Data are presented with 95% confidence intervals, unless otherwise stated; all treatment effects are estimates adjusted on age and centre. WHO-CPS: World Health Organization Clinical Progression Scale; NIV: noninvasive ventilation; IQR: interquartile range: ICU: intensive care unit; HR: hazard ratio; OR: odds ratio; MD: mean difference. #: NIV or high-flow oxygen; ¶: median posterior absolute risk difference with 90% credible intervals; +: median posterior HR adjusted for age and centre; §: median posterior OR adjusted for age and centre; ƒ: median posterior OR in a proportional odds model, adjusted for baseline WHO-CPS score, age and centre; ++: only for patients in the ICU at randomisation (TOCI-2 trial: n=40 in the tocilizumab arm and n=37 in the usual care arm; SARI-2 trial: n=38 in the sarilumab arm and n=28 in the usual care arm).