tetano
Editor, Senior Moderator
BMJ
. 2020 Jul 30;370:m2980.
doi: 10.1136/bmj.m2980.
Drug treatments for covid-19: living systematic review and network meta-analysis
Reed Ac Siemieniuk[SUP] 1 2 [/SUP], Jessica J Bartoszko[SUP] 3 2 [/SUP], Long Ge[SUP] 4 2 [/SUP], Dena Zeraatkar[SUP] 3 2 [/SUP], Ariel Izcovich[SUP] 5 [/SUP], Hector Pardo-Hernandez[SUP] 6 7 [/SUP], Bram Rochwerg[SUP] 3 8 [/SUP], Francois Lamontagne[SUP] 9 [/SUP], Mi Ah Han[SUP] 10 [/SUP], Elena Kum[SUP] 3 [/SUP], Qin Liu[SUP] 11 12 [/SUP], Arnav Agarwal[SUP] 3 13 [/SUP], Thomas Agoritsas[SUP] 3 14 [/SUP], Paul Alexander[SUP] 3 [/SUP], Derek K Chu[SUP] 3 8 [/SUP], Rachel Couban[SUP] 15 [/SUP], Andrea Darzi[SUP] 3 [/SUP], Tahira Devji[SUP] 3 [/SUP], Bo Fang[SUP] 11 12 [/SUP], Carmen Fang[SUP] 16 [/SUP], Signe Agnes Flottorp[SUP] 17 18 [/SUP], Farid Foroutan[SUP] 3 19 [/SUP], Diane Heels-Ansdell[SUP] 3 [/SUP], Kimia Honarmand[SUP] 5 [/SUP], Liangying Hou[SUP] 4 [/SUP], Xiaorong Hou[SUP] 20 [/SUP], Quazi Ibrahim[SUP] 3 [/SUP], Mark Loeb[SUP] 3 8 [/SUP], Maura Marcucci[SUP] 3 8 [/SUP], Shelley L McLeod[SUP] 21 22 [/SUP], Sharhzad Motaghi[SUP] 3 [/SUP], Srinivas Murthy[SUP] 23 [/SUP], Reem A Mustafa[SUP] 3 24 [/SUP], John D Neary[SUP] 5 [/SUP], Anila Qasim[SUP] 3 [/SUP], Gabriel Rada[SUP] 25 26 [/SUP], Irbaz Bin Riaz[SUP] 27 [/SUP], Behnam Sadeghirad[SUP] 3 15 [/SUP], Nigar Sekercioglu[SUP] 3 [/SUP], Lulu Sheng[SUP] 11 12 [/SUP], Charlotte Switzer[SUP] 3 [/SUP], Britta Tendal[SUP] 28 [/SUP], Lehana Thabane[SUP] 3 [/SUP], George Tomlinson[SUP] 29 [/SUP], Tari Turner[SUP] 28 [/SUP], Per O Vandvik[SUP] 16 [/SUP], Robin Wm Vernooij[SUP] 30 31 [/SUP], Andr?s Viteri-Garc?a[SUP] 25 32 [/SUP], Ying Wang[SUP] 3 [/SUP], Liang Yao[SUP] 3 [/SUP], Zhikang Ye[SUP] 3 [/SUP], Gordon H Guyatt[SUP] 3 8 [/SUP], Romina Brignardello-Petersen[SUP] 3 [/SUP]
Affiliations
Abstract
Objective: To compare the effects of treatments for coronavirus disease 2019 (covid-19).
Design: Living systematic review and network meta-analysis.
Data sources: US Centers for Disease Control and Prevention COVID-19 Research Articles Downloadable Database, which includes 25 electronic databases and six additional Chinese databases to 20 July 2020.
Study selection: Randomised clinical trials in which people with suspected, probable, or confirmed covid-19 were randomised to drug treatment or to standard care or placebo. Pairs of reviewers independently screened potentially eligible articles.
Methods: After duplicate data abstraction, a bayesian random effects network meta-analysis was conducted. Risk of bias of the included studies was assessed using a modification of the Cochrane risk of bias 2.0 tool, and the certainty of the evidence using the grading of recommendations assessment, development and evaluation (GRADE) approach. For each outcome, interventions were classified in groups from the most to the least beneficial or harmful following GRADE guidance.
Results: 23 randomised controlled trials were included in the analysis performed on 26 June 2020. The certainty of the evidence for most comparisons was very low because of risk of bias (lack of blinding) and serious imprecision. Glucocorticoids were the only intervention with evidence for a reduction in death compared with standard care (risk difference 37 fewer per 1000 patients, 95% credible interval 63 fewer to 11 fewer, moderate certainty) and mechanical ventilation (31 fewer per 1000 patients, 47 fewer to 9 fewer, moderate certainty). These estimates are based on direct evidence; network estimates for glucocorticoids compared with standard care were less precise because of network heterogeneity. Three drugs might reduce symptom duration compared with standard care: hydroxychloroquine (mean difference -4.5 days, low certainty), remdesivir (-2.6 days, moderate certainty), and lopinavir-ritonavir (-1.2 days, low certainty). Hydroxychloroquine might increase the risk of adverse events compared with the other interventions, and remdesivir probably does not substantially increase the risk of adverse effects leading to drug discontinuation. No other interventions included enough patients to meaningfully interpret adverse effects leading to drug discontinuation.
Conclusion: Glucocorticoids probably reduce mortality and mechanical ventilation in patients with covid-19 compared with standard care. The effectiveness of most interventions is uncertain because most of the randomised controlled trials so far have been small and have important study limitations.
Systematic review registration: This review was not registered. The protocol is included as a supplement.
Readers' note: This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication.
. 2020 Jul 30;370:m2980.
doi: 10.1136/bmj.m2980.
Drug treatments for covid-19: living systematic review and network meta-analysis
Reed Ac Siemieniuk[SUP] 1 2 [/SUP], Jessica J Bartoszko[SUP] 3 2 [/SUP], Long Ge[SUP] 4 2 [/SUP], Dena Zeraatkar[SUP] 3 2 [/SUP], Ariel Izcovich[SUP] 5 [/SUP], Hector Pardo-Hernandez[SUP] 6 7 [/SUP], Bram Rochwerg[SUP] 3 8 [/SUP], Francois Lamontagne[SUP] 9 [/SUP], Mi Ah Han[SUP] 10 [/SUP], Elena Kum[SUP] 3 [/SUP], Qin Liu[SUP] 11 12 [/SUP], Arnav Agarwal[SUP] 3 13 [/SUP], Thomas Agoritsas[SUP] 3 14 [/SUP], Paul Alexander[SUP] 3 [/SUP], Derek K Chu[SUP] 3 8 [/SUP], Rachel Couban[SUP] 15 [/SUP], Andrea Darzi[SUP] 3 [/SUP], Tahira Devji[SUP] 3 [/SUP], Bo Fang[SUP] 11 12 [/SUP], Carmen Fang[SUP] 16 [/SUP], Signe Agnes Flottorp[SUP] 17 18 [/SUP], Farid Foroutan[SUP] 3 19 [/SUP], Diane Heels-Ansdell[SUP] 3 [/SUP], Kimia Honarmand[SUP] 5 [/SUP], Liangying Hou[SUP] 4 [/SUP], Xiaorong Hou[SUP] 20 [/SUP], Quazi Ibrahim[SUP] 3 [/SUP], Mark Loeb[SUP] 3 8 [/SUP], Maura Marcucci[SUP] 3 8 [/SUP], Shelley L McLeod[SUP] 21 22 [/SUP], Sharhzad Motaghi[SUP] 3 [/SUP], Srinivas Murthy[SUP] 23 [/SUP], Reem A Mustafa[SUP] 3 24 [/SUP], John D Neary[SUP] 5 [/SUP], Anila Qasim[SUP] 3 [/SUP], Gabriel Rada[SUP] 25 26 [/SUP], Irbaz Bin Riaz[SUP] 27 [/SUP], Behnam Sadeghirad[SUP] 3 15 [/SUP], Nigar Sekercioglu[SUP] 3 [/SUP], Lulu Sheng[SUP] 11 12 [/SUP], Charlotte Switzer[SUP] 3 [/SUP], Britta Tendal[SUP] 28 [/SUP], Lehana Thabane[SUP] 3 [/SUP], George Tomlinson[SUP] 29 [/SUP], Tari Turner[SUP] 28 [/SUP], Per O Vandvik[SUP] 16 [/SUP], Robin Wm Vernooij[SUP] 30 31 [/SUP], Andr?s Viteri-Garc?a[SUP] 25 32 [/SUP], Ying Wang[SUP] 3 [/SUP], Liang Yao[SUP] 3 [/SUP], Zhikang Ye[SUP] 3 [/SUP], Gordon H Guyatt[SUP] 3 8 [/SUP], Romina Brignardello-Petersen[SUP] 3 [/SUP]
Affiliations
- PMID: 32732190
- DOI: 10.1136/bmj.m2980
Abstract
Objective: To compare the effects of treatments for coronavirus disease 2019 (covid-19).
Design: Living systematic review and network meta-analysis.
Data sources: US Centers for Disease Control and Prevention COVID-19 Research Articles Downloadable Database, which includes 25 electronic databases and six additional Chinese databases to 20 July 2020.
Study selection: Randomised clinical trials in which people with suspected, probable, or confirmed covid-19 were randomised to drug treatment or to standard care or placebo. Pairs of reviewers independently screened potentially eligible articles.
Methods: After duplicate data abstraction, a bayesian random effects network meta-analysis was conducted. Risk of bias of the included studies was assessed using a modification of the Cochrane risk of bias 2.0 tool, and the certainty of the evidence using the grading of recommendations assessment, development and evaluation (GRADE) approach. For each outcome, interventions were classified in groups from the most to the least beneficial or harmful following GRADE guidance.
Results: 23 randomised controlled trials were included in the analysis performed on 26 June 2020. The certainty of the evidence for most comparisons was very low because of risk of bias (lack of blinding) and serious imprecision. Glucocorticoids were the only intervention with evidence for a reduction in death compared with standard care (risk difference 37 fewer per 1000 patients, 95% credible interval 63 fewer to 11 fewer, moderate certainty) and mechanical ventilation (31 fewer per 1000 patients, 47 fewer to 9 fewer, moderate certainty). These estimates are based on direct evidence; network estimates for glucocorticoids compared with standard care were less precise because of network heterogeneity. Three drugs might reduce symptom duration compared with standard care: hydroxychloroquine (mean difference -4.5 days, low certainty), remdesivir (-2.6 days, moderate certainty), and lopinavir-ritonavir (-1.2 days, low certainty). Hydroxychloroquine might increase the risk of adverse events compared with the other interventions, and remdesivir probably does not substantially increase the risk of adverse effects leading to drug discontinuation. No other interventions included enough patients to meaningfully interpret adverse effects leading to drug discontinuation.
Conclusion: Glucocorticoids probably reduce mortality and mechanical ventilation in patients with covid-19 compared with standard care. The effectiveness of most interventions is uncertain because most of the randomised controlled trials so far have been small and have important study limitations.
Systematic review registration: This review was not registered. The protocol is included as a supplement.
Readers' note: This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication.