Ibrutinib and Acalabrutinib Use and Risk of Atrial Fibrillation in Patients With Chronic B-cell Malignancies

Background. Ibrutinib and acalabrutinib are both associated with an increased risk of atrial fibrillation (AF) but AF comparative risk between these 2 BTK inhibitors (BTKis) remains largely unknown.

Objectives. Our aim was to examine the risk of developing incident AF with ibrutinib exposure compared with acalabrutinib exposure.

Methods. Using the TriNetX research network database, authors will conduct a retrospective cohort analysis of deidentified, aggregate adult patients with chronic B-cell malignancies and exposed to ibrutinib or acalabrutinib. Patients will be divided into 2 groups based on ibrutinib or acalabrutinib exposure. After propensity score matching (PSM), hazard ratios (HRs) and their associated 95% confidence intervals (CIs) will be used to compare AF risk during follow-up between the matched 2 groups.

Study Overview

• Status: Active, not recruiting
• Conditions: Cardiovascular Diseases; Chronic B-cell Malignancies; BTK Inhibitors
• Intervention / Treatment: Drug: BTK inhibitor (Ibrutinib or Acalabrutinib)

• Study Type: Observational
• Enrollment (Estimated): 15000

Contacts and Locations

Study Locations

• France
  • Normandie
    • Caen, Normandie, France
      • Caen University Hospital, Department of Pharmacology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

adult patients - diagnose with chronic B-cell malignancies expose to ibrutinib or acalabrutinib in the TrinetX database

Description

Inclusion Criteria:

• adult patients
• diagnose with chronic B-cell malignancies using ICD-10-CM codes C91 (lymphoid leukemia), C88.0 (Waldenström macroglobulinemia), C83.1 (mantle cell lymphoma), C81-C96 (malignant neoplasms of lymphoid, hematopoietic and related tissue) or C95 (leukemia of unspecified cell type)
• expose to ibrutinib or acalabrutinib determined by the Anatomical Therapeutic Chemical codes

Exclusion Criteria:

-

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Ibrutinib; Adult patients with a chronic B-cell malignancy exposed to ibrutinib	Drug: BTK inhibitor (Ibrutinib or Acalabrutinib); Adult patients with a chronic B-cell malignancy included in this study will be separate into 2 groups according to the BTK inhibitor (ibrutinib and acalabrutinib)
Acalabrutinib; Adult patients with a chronic B-cell malignancy exposed to acalabrutinib	Drug: BTK inhibitor (Ibrutinib or Acalabrutinib); Adult patients with a chronic B-cell malignancy included in this study will be separate into 2 groups according to the BTK inhibitor (ibrutinib and acalabrutinib)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Risk of incident atrial fibrillation in patients exposed to ibrutinib compared with those exposed to acalabrutinib in the whole matched cohort.	ICD-10-CM code I48 will be used to identify AF during follow-up	from the introduction of the BTK inhibitor and up to 120 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Risk of all-cause mortality in patients exposed to ibrutinib compared with those exposed to acalabrutinib in the whole matched cohort	death from any cause during follow-up	from the introduction of the BTK inhibitor and up to 120 months
Risk of incident atrial fibrillation in patients exposed to ibrutinib compared with those exposed to acalabrutinib in a matched cohort restricted to patients aged ≤75 and to patients aged >75	ICD-10-CM code I48 will be used to identify AF during follow-up	from the introduction of the BTK inhibitor and up to 120 months
Risk of incident atrial fibrillation in patients exposed to ibrutinib compared with those exposed to acalabrutinib in a matched cohort categorized according their baseline cardiovascular risk level for developing AF	ICD-10-CM code ill be used to identify AF during follow-up	from the introduction of the BTK inhibitor and up to 120 months
Risk of incident intra-cerebral hemorrhage in patients exposed to ibrutinib compared with those exposed to acalabrutinib in the whole matched cohort	ICD-10-CM code ill be used to identify intra-cerebral hemorrhage during follow-up	from the introduction of the BTK inhibitor and up to 120 months
Risk of incident major bleeding in patients exposed to ibrutinib compared with those exposed to acalabrutinib in the whole matched cohort	ICD-10-CM code ill be used to identify major bleeding during follow-up	from the introduction of the BTK inhibitor and up to 120 months
Risk of incident hypertension in patients exposed to ibrutinib compared with those exposed to acalabrutinib in the whole matched cohort	ICD-10-CM code ill be used to identify hypertension during follow-up	from the introduction of the BTK inhibitor and up to 120 months
Risk of incident MACE (composite) in patients exposed to ibrutinib compared with those exposed to acalabrutinib in the whole matched cohort	ICD-10-CM code ill be used to identify MACE (composite of acute myocardial infraction, ischemic stroke or thromboembolism and heart failure) during follow-up	from the introduction of the BTK inhibitor and up to 120 months
Risk of incident ventricular tachycardia/ventricular fibrillation/cardiac arrest (composite) in patients exposed to ibrutinib compared with those exposed to acalabrutinib in the whole matched cohort	ICD-10-CM code ill be used to identify VT/VF/cardiac arrest (composite of ventricular tachycardia, ventricular fibrillation and cardiac arrest) during follow-up	from the introduction of the BTK inhibitor and up to 120 months

Collaborators and Investigators

• Sponsor: University Hospital, Caen

Study record dates

Study Major Dates

• Study Start (Actual): July 25, 2024
• Primary Completion (Estimated): September 30, 2024
• Study Completion (Estimated): October 30, 2024

Study Registration Dates

• First Submitted: July 24, 2024
• First Submitted That Met QC Criteria: August 17, 2024
• First Posted (Actual): August 20, 2024

Study Record Updates

• Last Update Posted (Actual): August 21, 2024
• Last Update Submitted That Met QC Criteria: August 19, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Arrhythmias, Cardiac; Neoplasms; Cardiovascular Diseases; Atrial Fibrillation; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Tyrosine Kinase Inhibitors; Acalabrutinib; Ibrutinib
• Other Study ID Numbers: Pharmaco072424

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Actually, data from TrinetX are only freely available for health care organizations participating to the health research network database.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No