tetano
Editor, Senior Moderator
J Infect Chemother
. 2024 Sep 24:S1341-321X(24)00265-4.
doi: 10.1016/j.jiac.2024.09.013. Online ahead of print. Tocilizumab in combination with standard of care in patients with severe COVID-19 pneumonia: efficacy and safety from a phase 3 clinical trial in Japan
Nobuyoshi Mori[SUP] 1 [/SUP], Toshihiro Nanki[SUP] 2 [/SUP], Akihiro Hirakawa[SUP] 3 [/SUP], Masaya Yamato[SUP] 4 [/SUP], Yuko Kaneko[SUP] 5 [/SUP], Rie Shiokawa[SUP] 6 [/SUP], Ryoto Ozaki[SUP] 6 [/SUP], Norihiro Kawabata[SUP] 6 [/SUP], Norio Ohmagari[SUP] 7 [/SUP]
Affiliations
Background: Coronavirus disease 2019 (COVID-19) is characterized by high interleukin-6 levels. Clinical data supporting tocilizumab, a monoclonal antibody that targets interleukin-6 receptor-alpha, for treating Japanese patients with severe COVID-19 pneumonia are needed.
Methods: This single-arm phase 3 study investigated tocilizumab (8 mg/kg) plus standard of care (SOC) in Japanese patients hospitalized with severe COVID-19 pneumonia. Clinical status was assessed using a 7-category ordinal scale on day 28 (primary endpoint) and day 14 (secondary endpoint). Other secondary endpoints were time to improvement (≥2 category improvement) and time to hospital discharge. Safety was assessed as the incidence of adverse events (AEs).
Results: Among 48 patients enrolled, 44 (91.7%) scored ≥3 on the 7-category ordinal scale at baseline. At day 28, 35 patients (72.9%) scored 1 and 5 (10.4%) scored 7 on the 7-category ordinal scale; 36 (75.0%, 95% confidence interval [CI]: 60.40-86.36%) and 39 (81.3%, 95% CI: 67.37-91.05%) patients achieved ≥2- and ≥1-category improvement, respectively; 6 patients (12.5%, 95% CI: 4.73-25.25%) demonstrated ≥1-category worsening. At day 14, 25 (52.1%, 95% CI: 37.19-66.71%) and 33 patients (68.8%, 95% CI: 53.75-81.34%) achieved ≥2- and ≥1-category improvement, respectively; 5 patients (10.4%, 95% CI: 3.47-22.66%) demonstrated ≥1-category worsening. Median times (95% CI) to improvement and hospital discharge were 11 (9-15) and 15 (11-18) days, respectively. Forty patients (83.3%) experienced AEs; the incidence of ≥grade 3 AEs was 25%.
Conclusion: Tocilizumab plus SOC may provide improved clinical status in Japanese patients with severe COVID-19 pneumonia; no new safety signals were identified.
Keywords: Biomarkers; COVID-19 pneumonia; Clinical trial; Efficacy; Interleukin-6; Safety; Severe acute respiratory syndrome coronavirus 2; Tocilizumab.
. 2024 Sep 24:S1341-321X(24)00265-4.
doi: 10.1016/j.jiac.2024.09.013. Online ahead of print. Tocilizumab in combination with standard of care in patients with severe COVID-19 pneumonia: efficacy and safety from a phase 3 clinical trial in Japan
Nobuyoshi Mori[SUP] 1 [/SUP], Toshihiro Nanki[SUP] 2 [/SUP], Akihiro Hirakawa[SUP] 3 [/SUP], Masaya Yamato[SUP] 4 [/SUP], Yuko Kaneko[SUP] 5 [/SUP], Rie Shiokawa[SUP] 6 [/SUP], Ryoto Ozaki[SUP] 6 [/SUP], Norihiro Kawabata[SUP] 6 [/SUP], Norio Ohmagari[SUP] 7 [/SUP]
Affiliations
- PMID: 39326494
- DOI: 10.1016/j.jiac.2024.09.013
Background: Coronavirus disease 2019 (COVID-19) is characterized by high interleukin-6 levels. Clinical data supporting tocilizumab, a monoclonal antibody that targets interleukin-6 receptor-alpha, for treating Japanese patients with severe COVID-19 pneumonia are needed.
Methods: This single-arm phase 3 study investigated tocilizumab (8 mg/kg) plus standard of care (SOC) in Japanese patients hospitalized with severe COVID-19 pneumonia. Clinical status was assessed using a 7-category ordinal scale on day 28 (primary endpoint) and day 14 (secondary endpoint). Other secondary endpoints were time to improvement (≥2 category improvement) and time to hospital discharge. Safety was assessed as the incidence of adverse events (AEs).
Results: Among 48 patients enrolled, 44 (91.7%) scored ≥3 on the 7-category ordinal scale at baseline. At day 28, 35 patients (72.9%) scored 1 and 5 (10.4%) scored 7 on the 7-category ordinal scale; 36 (75.0%, 95% confidence interval [CI]: 60.40-86.36%) and 39 (81.3%, 95% CI: 67.37-91.05%) patients achieved ≥2- and ≥1-category improvement, respectively; 6 patients (12.5%, 95% CI: 4.73-25.25%) demonstrated ≥1-category worsening. At day 14, 25 (52.1%, 95% CI: 37.19-66.71%) and 33 patients (68.8%, 95% CI: 53.75-81.34%) achieved ≥2- and ≥1-category improvement, respectively; 5 patients (10.4%, 95% CI: 3.47-22.66%) demonstrated ≥1-category worsening. Median times (95% CI) to improvement and hospital discharge were 11 (9-15) and 15 (11-18) days, respectively. Forty patients (83.3%) experienced AEs; the incidence of ≥grade 3 AEs was 25%.
Conclusion: Tocilizumab plus SOC may provide improved clinical status in Japanese patients with severe COVID-19 pneumonia; no new safety signals were identified.
Keywords: Biomarkers; COVID-19 pneumonia; Clinical trial; Efficacy; Interleukin-6; Safety; Severe acute respiratory syndrome coronavirus 2; Tocilizumab.