tetano
Editor, Senior Moderator
J Clin Med
. 2021 Oct 25;10(21):4935.
doi: 10.3390/jcm10214935.
The Use of Tocilizumab in Patients with COVID-19: A Systematic Review, Meta-Analysis and Trial Sequential Analysis of Randomized Controlled Studies
Alberto Enrico Maraolo[SUP] 1 [/SUP], Anna Crispo[SUP] 2 [/SUP], Michela Piezzo[SUP] 3 [/SUP], Piergiacomo Di Gennaro[SUP] 2 [/SUP], Maria Grazia Vitale[SUP] 4 [/SUP], Domenico Mallardo[SUP] 4 [/SUP], Luigi Ametrano[SUP] 5 [/SUP], Egidio Celentano[SUP] 2 [/SUP], Arturo Cuomo[SUP] 6 [/SUP], Paolo A Ascierto[SUP] 4 [/SUP], Marco Cascella[SUP] 6 [/SUP]
Affiliations
Abstract
Background: Among the several therapeutic options assessed for the treatment of coronavirus disease 2019 (COVID-19), tocilizumab (TCZ), an antagonist of the interleukine-6 receptor, has emerged as a promising therapeutic choice, especially for the severe form of the disease. Proper synthesis of the available randomized clinical trials (RCTs) is needed to inform clinical practice.
Methods: A systematic review with a meta-analysis of RCTs investigating the efficacy of TCZ in COVID-19 patients was conducted. PubMed, EMBASE, and the Cochrane COVID-19 Study Register were searched up until 30 April 2021.
Results: The database search yielded 2885 records; 11 studies were considered eligible for full-text review, and nine met the inclusion criteria. Overall, 3358 patients composed the TCZ arm, and 3131 the comparator group. The main outcome was all-cause mortality at 28-30 days. Subgroup analyses according to trials' and patients' features were performed. A trial sequential analysis (TSA) was also carried out to minimize type I and type II errors. According to the fixed-effect model approach, TCZ was associated with a better survival odds ratio (OR) (0.84; 95% confidence interval (CI): 0.75-0.94; I[SUP]2[/SUP]: 24% (low heterogeneity)). The result was consistent in the subgroup of severe disease (OR: 0.83; 95% CI: 0.74-0.93; I[SUP]2[/SUP]: 53% (moderate heterogeneity)). However, the TSA illustrated that the required information size was not met unless the study that was the major source of heterogeneity was omitted.
Conclusions: TCZ may represent an important weapon against severe COVID-19. Further studies are needed to consolidate this finding.
Keywords: COVID-19; COVID-19 pneumonia; SARS-CoV-2; meta-analysis; tocilizumab; trial sequential analysis.
. 2021 Oct 25;10(21):4935.
doi: 10.3390/jcm10214935.
The Use of Tocilizumab in Patients with COVID-19: A Systematic Review, Meta-Analysis and Trial Sequential Analysis of Randomized Controlled Studies
Alberto Enrico Maraolo[SUP] 1 [/SUP], Anna Crispo[SUP] 2 [/SUP], Michela Piezzo[SUP] 3 [/SUP], Piergiacomo Di Gennaro[SUP] 2 [/SUP], Maria Grazia Vitale[SUP] 4 [/SUP], Domenico Mallardo[SUP] 4 [/SUP], Luigi Ametrano[SUP] 5 [/SUP], Egidio Celentano[SUP] 2 [/SUP], Arturo Cuomo[SUP] 6 [/SUP], Paolo A Ascierto[SUP] 4 [/SUP], Marco Cascella[SUP] 6 [/SUP]
Affiliations
- PMID: 34768455
- DOI: 10.3390/jcm10214935
Abstract
Background: Among the several therapeutic options assessed for the treatment of coronavirus disease 2019 (COVID-19), tocilizumab (TCZ), an antagonist of the interleukine-6 receptor, has emerged as a promising therapeutic choice, especially for the severe form of the disease. Proper synthesis of the available randomized clinical trials (RCTs) is needed to inform clinical practice.
Methods: A systematic review with a meta-analysis of RCTs investigating the efficacy of TCZ in COVID-19 patients was conducted. PubMed, EMBASE, and the Cochrane COVID-19 Study Register were searched up until 30 April 2021.
Results: The database search yielded 2885 records; 11 studies were considered eligible for full-text review, and nine met the inclusion criteria. Overall, 3358 patients composed the TCZ arm, and 3131 the comparator group. The main outcome was all-cause mortality at 28-30 days. Subgroup analyses according to trials' and patients' features were performed. A trial sequential analysis (TSA) was also carried out to minimize type I and type II errors. According to the fixed-effect model approach, TCZ was associated with a better survival odds ratio (OR) (0.84; 95% confidence interval (CI): 0.75-0.94; I[SUP]2[/SUP]: 24% (low heterogeneity)). The result was consistent in the subgroup of severe disease (OR: 0.83; 95% CI: 0.74-0.93; I[SUP]2[/SUP]: 53% (moderate heterogeneity)). However, the TSA illustrated that the required information size was not met unless the study that was the major source of heterogeneity was omitted.
Conclusions: TCZ may represent an important weapon against severe COVID-19. Further studies are needed to consolidate this finding.
Keywords: COVID-19; COVID-19 pneumonia; SARS-CoV-2; meta-analysis; tocilizumab; trial sequential analysis.