Bleeding risk with concurrent use of anticoagulants and ibrutinib: A population-based nested case-control study
Corresponding Author
Marion Allouchery
Pharmacologie Clinique et Vigilances, CHU de Poitiers, Poitiers, France
Faculté de Médecine, Université de Poitiers, Poitiers, France
Univ. Bordeaux, INSERM, BPH, U1219, Team AHeaD, Bordeaux, France
Correspondence
Marion Allouchery, Pharmacologie Clinique et Vigilances, CHU de Poitiers, 2 rue de la Milétrie, 86021 Poitiers Cedex, France.
Email: [email protected]
Search for more papers by this authorCécile Tomowiak
Onco-Hématologie et Thérapie Cellulaire, CHU de Poitiers, Poitiers, France
INSERM CIC 1402, CHU de Poitiers, Poitiers, France
Search for more papers by this authorAllison Singier
Univ. Bordeaux, INSERM, BPH, U1219, Team AHeaD, Bordeaux, France
Search for more papers by this authorMathieu Puyade
INSERM CIC 1402, CHU de Poitiers, Poitiers, France
Médecine Interne et Maladies Infectieuses, CHU de Poitiers, Poitiers, France
Search for more papers by this authorLoubna Dari
Univ. Bordeaux, INSERM, BPH, U1219, Team AHeaD, Bordeaux, France
Médecine Vasculaire, CHU de Bordeaux, Bordeaux, France
Search for more papers by this authorElodie Pambrun
Univ. Bordeaux, INSERM, BPH, U1219, Team AHeaD, Bordeaux, France
Search for more papers by this authorAntoine Pariente
Univ. Bordeaux, INSERM, BPH, U1219, Team AHeaD, Bordeaux, France
Search for more papers by this authorJulien Bezin
Univ. Bordeaux, INSERM, BPH, U1219, Team AHeaD, Bordeaux, France
CHU de Bordeaux, Pôle de Santé Publique, Service de Pharmacologie Médicale, Bordeaux, France
Search for more papers by this authorMarie-Christine Pérault-Pochat
Pharmacologie Clinique et Vigilances, CHU de Poitiers, Poitiers, France
Laboratoire de Neurosciences Expérimentales et Cliniques, INSERM, UMR1084, Université de Poitiers, Poitiers, France
Search for more papers by this authorFrancesco Salvo
Univ. Bordeaux, INSERM, BPH, U1219, Team AHeaD, Bordeaux, France
CHU de Bordeaux, Pôle de Santé Publique, Service de Pharmacologie Médicale, Bordeaux, France
Search for more papers by this authorCorresponding Author
Marion Allouchery
Pharmacologie Clinique et Vigilances, CHU de Poitiers, Poitiers, France
Faculté de Médecine, Université de Poitiers, Poitiers, France
Univ. Bordeaux, INSERM, BPH, U1219, Team AHeaD, Bordeaux, France
Correspondence
Marion Allouchery, Pharmacologie Clinique et Vigilances, CHU de Poitiers, 2 rue de la Milétrie, 86021 Poitiers Cedex, France.
Email: [email protected]
Search for more papers by this authorCécile Tomowiak
Onco-Hématologie et Thérapie Cellulaire, CHU de Poitiers, Poitiers, France
INSERM CIC 1402, CHU de Poitiers, Poitiers, France
Search for more papers by this authorAllison Singier
Univ. Bordeaux, INSERM, BPH, U1219, Team AHeaD, Bordeaux, France
Search for more papers by this authorMathieu Puyade
INSERM CIC 1402, CHU de Poitiers, Poitiers, France
Médecine Interne et Maladies Infectieuses, CHU de Poitiers, Poitiers, France
Search for more papers by this authorLoubna Dari
Univ. Bordeaux, INSERM, BPH, U1219, Team AHeaD, Bordeaux, France
Médecine Vasculaire, CHU de Bordeaux, Bordeaux, France
Search for more papers by this authorElodie Pambrun
Univ. Bordeaux, INSERM, BPH, U1219, Team AHeaD, Bordeaux, France
Search for more papers by this authorAntoine Pariente
Univ. Bordeaux, INSERM, BPH, U1219, Team AHeaD, Bordeaux, France
Search for more papers by this authorJulien Bezin
Univ. Bordeaux, INSERM, BPH, U1219, Team AHeaD, Bordeaux, France
CHU de Bordeaux, Pôle de Santé Publique, Service de Pharmacologie Médicale, Bordeaux, France
Search for more papers by this authorMarie-Christine Pérault-Pochat
Pharmacologie Clinique et Vigilances, CHU de Poitiers, Poitiers, France
Laboratoire de Neurosciences Expérimentales et Cliniques, INSERM, UMR1084, Université de Poitiers, Poitiers, France
Search for more papers by this authorFrancesco Salvo
Univ. Bordeaux, INSERM, BPH, U1219, Team AHeaD, Bordeaux, France
CHU de Bordeaux, Pôle de Santé Publique, Service de Pharmacologie Médicale, Bordeaux, France
Search for more papers by this authorFrancesco Salvo and Marie-Christine Pérault-Pochat contributed equally to this study.
Summary
Data regarding the safety of co-administration of ibrutinib with anticoagulants in real-life settings are scarce. Using a nationwide database, we conducted a nested case-control study in a cohort of new users of ibrutinib to assess the risk of clinically relevant bleeding (CRB) associated with anticoagulation. Cases were patients with a diagnosis of CRB, defined as hospitalization with a diagnosis of bleeding. The date of CRB constituted the index date. Up to four controls were matched on sex, age at index date and duration of follow-up. The risk of CRB associated with anticoagulation in patients receiving ibrutinib was estimated using conditional logistic regression models, providing odds ratios (OR) adjusted for risk factors of bleeding. Among 614 cases and 2407 matched controls, the risk of CRB was significantly higher in patients receiving both ibrutinib and anticoagulants (adjusted OR [aOR] 2.54, confidence interval [CI] 95% [1.94; 3.32]). When considering anticoagulant class, aOR was 1.99 (CI 95% [1.19; 3.33]) for VKA, 2.48 (CI 95% [1.76; 3.47]) for direct oral anticoagulants and 3.40 (CI 95% [2.01; 5.75]) for parenteral anticoagulants. In conclusion, this study found a 2.5-fold increased risk of CRB in patients receiving both ibrutinib and anticoagulants in real-life settings, and similar aOR among oral anticoagulants.
Graphical Abstract
Bleeding risk with concurrent use of anticoagulants and ibrutinib: A population-based nested case-control study.
CONFLICT OF INTEREST STATEMENT
The authors declare no conflicts of interest.
Open Research
DATA AVAILABILITY STATEMENT
According to data protection and French regulations, the authors cannot publicly release the data from the French National Healthcare Database (SNDS). However, any person or organization (public or private; for-profit or non-profit) can access anonymized SNDS data to perform a study, research or an evaluation of public interest, upon authorization from an independent ethics and scientific committee (CESREES) and the French Data Protection Office (CNIL) (https://www.health-data-hub.fr/page/faq-english).
Supporting Information
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Data S1. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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