Yeming Wang1,2,3, Guohui Fan1,2,4, Alex Salam5, Peter Horby5, Frederick G Hayden6, Cheng Chen7, Jianguang Pan8, Jing Zheng9, Binghuai Lu1,2, Liping Guo1, Chen Wang1,2,3, Bin Cao1,2,3. 1. Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, China-Japan Friendship Hospital, Beijing, China. 2. Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China. 3. Department of Respiratory Medicine, Capital Medical University, Beijing, China. 4. Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, China. 5. Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, United Kingdom. 6. Department of Medicine, University of Virginia School of Medicine, Charlottesville, Virginia, USA. 7. Department of Pulmonary and Critical Care Medicine, First Affiliated Hospital of Soochow University, Jiangsu Province, China. 8. Department of Pulmonary and Critical Care Medicine, Fuzhou Pulmonary Hospital of Fujian, Fujian Province, China. 9. Fifth Medical Centre, Chinese People's Liberation Army General Hospital, Beijing, China.
Abstract
BACKGROUND: A synergistic effect of combination therapy with favipiravir and oseltamivir has been reported in preclinical models of influenza. However, no data are available on the clinical effectiveness of combination therapy in severe influenza. METHODS: Data from 2 separate prospective studies of influenza adults were used to compare outcomes between combination and oseltamivir monotherapy. Outcomes included rate of clinical improvement (defined as a decrease of 2 categories on a 7-category ordinal scale) and viral RNA detectability over time. Subhazard ratios (sHRs) were estimated by the Fine and Gray model for competing risks. RESULTS: In total, 40 patients were treated with combination therapy and 128 with oseltamivir alone. Clinical improvement on day 14 in the combination group was higher than in the monotherapy group (62.5% vs 42.2%; P = .0247). The adjusted sHR for combination therapy was 2.06 (95% confidence interval, 1.30-3.26). The proportion of undetectable viral RNA at day 10 was higher in the combination group than the oseltamivir group (67.5% vs 21.9%; P < .01). No significant differences were observed in mortality or other outcomes. CONCLUSIONS:Favipiravir and oseltamivir combination therapy may accelerate clinical recovery compared to oseltamivir monotherapy in severe influenza, and this strategy should be formally evaluated in a randomized controlled trial.
RCT Entities:
BACKGROUND: A synergistic effect of combination therapy with favipiravir and oseltamivir has been reported in preclinical models of influenza. However, no data are available on the clinical effectiveness of combination therapy in severe influenza. METHODS: Data from 2 separate prospective studies of influenza adults were used to compare outcomes between combination and oseltamivir monotherapy. Outcomes included rate of clinical improvement (defined as a decrease of 2 categories on a 7-category ordinal scale) and viral RNA detectability over time. Subhazard ratios (sHRs) were estimated by the Fine and Gray model for competing risks. RESULTS: In total, 40 patients were treated with combination therapy and 128 with oseltamivir alone. Clinical improvement on day 14 in the combination group was higher than in the monotherapy group (62.5% vs 42.2%; P = .0247). The adjusted sHR for combination therapy was 2.06 (95% confidence interval, 1.30-3.26). The proportion of undetectable viral RNA at day 10 was higher in the combination group than the oseltamivir group (67.5% vs 21.9%; P < .01). No significant differences were observed in mortality or other outcomes. CONCLUSIONS:Favipiravir and oseltamivir combination therapy may accelerate clinical recovery compared to oseltamivir monotherapy in severe influenza, and this strategy should be formally evaluated in a randomized controlled trial.
Authors: Stanislaw P Stawicki; Rebecca Jeanmonod; Andrew C Miller; Lorenzo Paladino; David F Gaieski; Anna Q Yaffee; Annelies De Wulf; Joydeep Grover; Thomas J Papadimos; Christina Bloem; Sagar C Galwankar; Vivek Chauhan; Michael S Firstenberg; Salvatore Di Somma; Donald Jeanmonod; Sona M Garg; Veronica Tucci; Harry L Anderson; Lateef Fatimah; Tamara J Worlton; Siddharth P Dubhashi; Krystal S Glaze; Sagar Sinha; Ijeoma Nnodim Opara; Vikas Yellapu; Dhanashree Kelkar; Ayman El-Menyar; Vimal Krishnan; S Venkataramanaiah; Yan Leyfman; Hassan Ali Saoud Al Thani; Prabath Wb Nanayakkara; Sudip Nanda; Eric Cioè-Peña; Indrani Sardesai; Shruti Chandra; Aruna Munasinghe; Vibha Dutta; Silvana Teixeira Dal Ponte; Ricardo Izurieta; Juan A Asensio; Manish Garg Journal: J Glob Infect Dis Date: 2020-05-22
Authors: Michael G Ison; Frederick G Hayden; Alan J Hay; Larisa V Gubareva; Elena A Govorkova; Emi Takashita; Jennifer L McKimm-Breschkin Journal: Antiviral Res Date: 2021-08-04 Impact factor: 10.103