The Use of Tocilizumab in Patients with COVID-19: A Systematic Review, Meta-Analysis and Trial Sequential Analysis of Randomized Controlled Studies

Journal of Clinical Medicine

卷:10

Luigi Ametrano¹  Paolo A. Ascierto²  Domenico Mallardo²  Maria Grazia Vitale²  Michela Piezzo³  Arturo Cuomo⁴  Marco Cascella⁴  Piergiacomo Di Gennaro⁵  Egidio Celentano⁵  Anna Crispo⁵  Alberto Enrico Maraolo⁶ 

[1] Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples Federico II, 80131 Naples, Italy;

[2] Department of Melanoma, Cancer Immunotherapy and Development Therapeutics, Istituto NazionaleTumori, IRCCS Fondazione G. Pascale, 80131 Naples, Italy;

[3] Department of Public Health and Infectious Diseases, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy;

[4] Division of Anesthesia and Pain Medicine, Istituto Nazionale Tumori, IRCCS Fondazione G. Pascale, 80131 Naples, Italy;

[5] Epidemiology and Biostatistics Unit, Istituto Nazionale Tumori, IRCCS Fondazione G. Pascale, 80131 Naples, Italy;

[6] First Division of Infectious Diseases, Cotugno Hospital, AORN dei Colli, 80131 Naples, Italy;

关键词: COVID-19 pneumonia;    tocilizumab;    SARS-CoV-2;    COVID-19;    meta-analysis;    trial sequential analysis;   

DOI  :  10.3390/jcm10214935

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown