Differences in Neutrophil Counts Between African and Non-African Countries in 2 International Clinical Trials

Area of Science:

• Pharmacovigilance
• Clinical Trial Analysis
• Hematology

Background:

• Observed differences in absolute neutrophil count (ANC) between African and non-African populations.
• Potential for neutropenia during rifamycin use.
• Limitations of current severity grading criteria (CTCAE, DAIDS) across diverse populations.

Purpose of the Study:

• To investigate the association between African ancestry and neutropenia during tuberculosis treatment.
• To evaluate the impact of different rifapentine dosing on neutropenia incidence.
• To assess the applicability of CTCAE and DAIDS criteria for grading neutropenia in African populations.

Main Methods:

• Analysis of ANC data from 2 international tuberculosis treatment trials.
• Comparison of ANC at baseline and over 12 weeks of treatment with rifampin and varying doses of rifapentine.
• Evaluation of neutropenia events using CTCAE and DAIDS criteria.

Main Results:

• Lower baseline median ANC observed in Black African participants compared to Black non-African participants.
• Enrollment in an African country was an independent factor associated with neutropenia development.
• CTCAE and DAIDS criteria yielded significantly different neutropenia event counts.

Conclusions:

• Differences in baseline ANC can lead to misclassification of adverse events and inappropriate clinical management.
• Development of population-specific normal ANC values is crucial for improved research and clinical guidance.
• Neutropenia events observed were transient and resolved without treatment interruption.