Use of repurposed and adjuvant drugs in hospital patients with covid-19: multinational network cohort study,The BMJ

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Use of repurposed and adjuvant drugs in hospital patients with covid-19: multinational network cohort study
The BMJ ( IF 93.6 ) Pub Date : 2021-05-11 , DOI: 10.1136/bmj.n1038
Albert Prats-Uribe ₁ , Anthony G Sena _{2,

3} , Lana Yin Hui Lai ₄ , Waheed-Ul-Rahman Ahmed _{5,

6} , Heba Alghoul ₇ , Osaid Alser ₈ , Thamir M Alshammari ₉ , Carlos Areia ₁₀ , William Carter ₁₁ , Paula Casajust ₁₂ , Dalia Dawoud _{13,

14} , Asieh Golozar _{15,

16} , Jitendra Jonnagaddala ₁₇ , Paras P Mehta ₁₈ , Mengchun Gong ₁₉ , Daniel R Morales _{20,

21} , Fredrik Nyberg ₂₂ , Jose D Posada ₂₃ , Martina Recalde _{24,

25} , Elena Roel _{24,

25} , Karishma Shah ₅ , Nigam H Shah ₂₃ , Lisa M Schilling ₁₁ , Vignesh Subbian ₂₆ , David Vizcaya ₂₇ , Lin Zhang _{28,

29} , Ying Zhang ₁₉ , Hong Zhu ₃₀ , Li Liu ₃₀ , Jaehyeong Cho ₃₁ , Kristine E Lynch ₃₂ , Michael E Matheny _{33,

34} , Seng Chan You ₃₅ , Peter R Rijnbeek ₃ , George Hripcsak ₃₆ , Jennifer Ce Lane ₅ , Edward Burn _{1,

24} , Christian Reich ₃₇ , Marc A Suchard ₃₈ , Talita Duarte-Salles ₂₄ , Kristin Kostka _{37,

39} , Patrick B Ryan _{40,

41} , Daniel Prieto-Alhambra ₁

Affiliation

Pharmaco- and Device Epidemiology, Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
Janssen Research and Development, Titusville, NJ, USA.
Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, Netherlands.
Division of Cancer Sciences, School of Medical Sciences, University of Manchester, Manchester, UK.
Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
College of Medicine and Health, University of Exeter, Exeter, UK.
Faculty of Medicine, Islamic University of Gaza, Gaza City, Palestine.
Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
College of Pharmacy, Riyadh Elm University, Riyadh, Saudi Arabia.
Critical Care Research Group, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Real-World Evidence, Trial Form Support, Barcelona, Spain.
Faculty of Pharmacy, Cairo University, Cairo, Egypt.
National Institute for Health and Care Excellence, London, UK.
Regeneron Pharmaceuticals, Tarrytown, NY, US.
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
School of Population Health, UNSW Sydney, Sydney, Australia.
College of Medicine, University of Arizona, Tucson, AZ, USA.
DHC Technologies, Beijing, China.
Division of Population Health and Genomics, University of Dundee, Dundee, UK.
Department of Public Health, University of Southern Denmark, Odense, Denmark.
School of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Fundació Institut Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain.
Universitat Autònoma de Barcelona, Barcelona, Spain.
College of Engineering, University of Arizona Tucson, AZ, USA.
Bayer Pharmaceuticals, Sant Joan Despí, Spain.
School of Population Medicine and Public Health, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
School of Population and Global Health, University of Melbourne, Melbourne, VIC, Australia.
Nanfang University, Southern Medical University, Guangzhou, China.
Department of Biomedical Informatics, Ajou University School of Medicine, Suwon, South Korea.
VA Informatics and Computing Infrastructure, VA Salt Lake City Healthcare System, Salt Lake City, Utah, USA; Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA.
VA Informatics and Computing Infrastructure, Tennessee Valley Healthcare System, VA Medical Center, Nashville, TN, USA.
Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, USA.
Department of Preventive Medicine and Public Health, Yonsei University College of Medicine, Seoul, South Korea.
Department of Biomedical Informatics, Columbia University, New York, NY, USA.
IQVIA, Cambridge, MA, USA.
Department of Biostatistics, UCLA Fielding School of Public Health, University of California, Los Angeles, Los Angeles, CA, USA.
OHDSI Center at The Roux Institute, Northeastern University, Portland, ME, USA.
Janssen Research and Development, Titusville, NJ, USA
Columbia University Irving Medical Center, New York, NY, USA.

Objective To investigate the use of repurposed and adjuvant drugs in patients admitted to hospital with covid-19 across three continents. Design Multinational network cohort study. Setting Hospital electronic health records from the United States, Spain, and China, and nationwide claims data from South Korea. Participants 303 264 patients admitted to hospital with covid-19 from January 2020 to December 2020. Main outcome measures Prescriptions or dispensations of any drug on or 30 days after the date of hospital admission for covid-19. Results Of the 303 264 patients included, 290 131 were from the US, 7599 from South Korea, 5230 from Spain, and 304 from China. 3455 drugs were identified. Common repurposed drugs were hydroxychloroquine (used in from <5 (<2%) patients in China to 2165 (85.1%) in Spain), azithromycin (from 15 (4.9%) in China to 1473 (57.9%) in Spain), combined lopinavir and ritonavir (from 156 (<2%) in the VA-OMOP US to 2,652 (34.9%) in South Korea and 1285 (50.5%) in Spain), and umifenovir (0% in the US, South Korea, and Spain and 238 (78.3%) in China). Use of adjunctive drugs varied greatly, with the five most used treatments being enoxaparin, fluoroquinolones, ceftriaxone, vitamin D, and corticosteroids. Hydroxychloroquine use increased rapidly from March to April 2020 but declined steeply in May to June and remained low for the rest of the year. The use of dexamethasone and corticosteroids increased steadily during 2020. Conclusions Multiple drugs were used in the first few months of the covid-19 pandemic, with substantial geographical and temporal variation. Hydroxychloroquine, azithromycin, lopinavir-ritonavir, and umifenovir (in China only) were the most prescribed repurposed drugs. Antithrombotics, antibiotics, H2 receptor antagonists, and corticosteroids were often used as adjunctive treatments. Research is needed on the comparative risk and benefit of these treatments in the management of covid-19.

更新日期：2021-05-11

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