Phenotype Algorithms for the Identification and Characterization of Vaccine-Induced Thrombotic Thrombocytopenia in Real World Data: A Multinational Network Cohort Study

Azza Shoaibi*, Gowtham A. Rao, Erica A. Voss, Anna Ostropolets, Miguel Angel Mayer, Juan Manuel Ramírez-Anguita, Filip Maljković, Biljana Carević, Scott Horban, Daniel R. Morales, Talita Duarte-Salles, Clement Fraboulet, Tanguy Le Carrour, Spiros Denaxas, Vaclav Papez, Luis H. John, Peter R. Rijneek, Evan Minty, Thamir M. Alshammari, Rupa MakadiaClair Blacketer, Frank DeFalco, Anthony G. Sena, Marc A. Suchard, Daniel Prieto-Alhambra, Patrick B. Ryan

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Introduction: Vaccine-induced thrombotic thrombocytopenia (VITT) has been identified as a rare but serious adverse event associated with coronavirus disease 2019 (COVID-19) vaccines. Objectives: In this study, we explored the pre-pandemic co-occurrence of thrombosis with thrombocytopenia (TWT) using 17 observational health data sources across the world. We applied multiple TWT definitions, estimated the background rate of TWT, characterized TWT patients, and explored the makeup of thrombosis types among TWT patients. Methods: We conducted an international network retrospective cohort study using electronic health records and insurance claims data, estimating background rates of TWT amongst persons observed from 2017 to 2019. Following the principles of existing VITT clinical definitions, TWT was defined as patients with a diagnosis of embolic or thrombotic arterial or venous events and a diagnosis or measurement of thrombocytopenia within 7 days. Six TWT phenotypes were considered, which varied in the approach taken in defining thrombosis and thrombocytopenia in real world data. Results: Overall TWT incidence rates ranged from 1.62 to 150.65 per 100,000 person-years. Substantial heterogeneity exists across data sources and by age, sex, and alternative TWT phenotypes. TWT patients were likely to be men of older age with various comorbidities. Among the thrombosis types, arterial thrombotic events were the most common. Conclusion: Our findings suggest that identifying VITT in observational data presents a substantial challenge, as implementing VITT case definitions based on the co-occurrence of TWT results in large and heterogeneous incidence rate and in a cohort of patints with baseline characteristics that are inconsistent with the VITT cases reported to date.

Original languageEnglish
Pages (from-to)685-698
Number of pages14
JournalDrug Safety
Volume45
Issue number6
DOIs
Publication statusPublished - 2 Jun 2022

Bibliographical note

Funding Information:
AS, GR, EAV, RM, AGS, CB, FD, and PBR are employees of Janssen Biotech Inc., a Janssen Pharmaceutical Company of Johnson & Johnson and shareholder of Johnson & Johnson, the product manufacturer of Janssen COVID-19 Vaccine. PRR is an employee of an institution that receives/received research grants from Janssen Research and Development LLC. DPA’s research group has received research grants from the European Medicines Agency, from the Innovative Medicines Initiative, and from Amgen, Chiesi, and UCB Biopharma; and consultancy or speaker fees from Astellas, Amgen, and UCB Biopharma. AO has received funding from the US National Institutes of Health and the US Food and Drug Administration. MAS receives grants and contracts from the US Food and Drug Administration and the US Department of Veterans Affairs within the scope of this research, and grants and contracts from the US National Institutes of Health, IQVIA, and Private Health Management outside the scope of this research. MAM, JMRA, FM, BC, SH, DRM, TDS, CF, TC, SD, VP, LHJ, EM, and TMA have no conflicts of interest to declare that are directly relevant to the contents of this study.

Funding Information:
This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 806968. The JU receives support from the European Union’s Horizon 2020 research and innovation program and EFPIA. Funders had no role in the conceptualization, design, data collection, analysis, decision to publish, or preparation of the manuscript.

Publisher Copyright:
© 2022, The Author(s).

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