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The Use of Tocilizumab in Patients with COVID-19: A Systematic Review, Meta-Analysis and Trial Sequential Analysis of
Alberto Enrico Maraolo1, Anna Crispo2, Michela Piezzo3
1First Division of Infectious Diseases, Cotugno Hospital, AORN dei Colli, 80131 Naples, Italy.
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; I2: 24% (low heterogeneity)). The result was consistent in the subgroup of severe disease (OR: 0.83; 95% CI: 0.74-0.93; I2: 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.
Insights
Tocilizumab (TCZ) shows promise in treating severe COVID-19 by improving survival rates. However, further research is required to confirm these findings and address study limitations.
Area of Science:
- Immunology
- Pharmacology
- Infectious Diseases
Background:
- Tocilizumab (TCZ), an interleukin-6 receptor antagonist, is a potential treatment for coronavirus disease 2019 (COVID-19).
- TCZ is particularly considered for severe cases of COVID-19.
- A synthesis of randomized clinical trials (RCTs) is necessary to guide clinical practice.
Purpose of the Study:
- To conduct a systematic review and meta-analysis of RCTs evaluating TCZ efficacy in COVID-19 patients.
- To assess the impact of TCZ on all-cause mortality in COVID-19.
Main Methods:
- Systematic review and meta-analysis of RCTs.
- Searched PubMed, EMBASE, and Cochrane COVID-19 Study Register up to April 30, 2021.
- Included 9 studies with 3358 patients in the TCZ arm and 3131 in the comparator group.
- Performed subgroup analyses and trial sequential analysis (TSA).
Main Results:
- TCZ was associated with improved survival (OR: 0.84; 95% CI: 0.75-0.94) with low heterogeneity (I²: 24%).
- The benefit was consistent in severe COVID-19 cases (OR: 0.83; 95% CI: 0.74-0.93) with moderate heterogeneity (I²: 53%).
- TSA indicated that the required information size was not met without excluding a major source of heterogeneity.
Conclusions:
- Tocilizumab may be a valuable therapeutic option for severe COVID-19.
- Further research is needed to confirm the efficacy and optimal use of TCZ in COVID-19 management.
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