Setting up pharmacovigilance based on available endTB Project data for bedaquiline

Area of Science:

• Pharmacovigilance and Drug Safety
• Tuberculosis Treatment
• Clinical Pharmacology

Background:

• Active pharmacovigilance (PV) is crucial for tuberculosis (TB) programs, especially for multidrug-resistant TB (MDR-TB) patients on new drugs.
• The endTB initiative, supported by UNITAID, facilitated the use of bedaquiline (BDQ) and/or delamanid for over 2600 patients across 17 countries.
• A central PV unit (PVU) was established to manage and analyze safety data.

Purpose of the Study:

• To detail the pharmacovigilance unit (PVU) process within the endTB initiative.
• To describe serious adverse events (SAEs) observed in patients treated with bedaquiline (BDQ)-containing regimens.
• To identify safety signals associated with new TB drugs.

Main Methods:

• Implemented an advanced TB drug safety monitoring and management (aDSM) system aligned with WHO guidelines.
• Monitored all clinically significant adverse events (AEs), with a focus on SAE detection by the PVU.
• A panel of MDR-TB and PV experts reviewed unexpected and potentially drug-related SAEs to identify safety signals.

Main Results:

• Between April 2015 and March 2019, the PVU processed 626 SAEs from 417 patients receiving BDQ.
• Expert review identified safety signals, highlighting risk factors such as polypharmacy and off-label drug use.
• The findings emphasized the importance of a patient-centered approach in managing complex TB treatment regimens.

Conclusions:

• Organizing advanced pharmacovigilance within routine healthcare settings is achievable but resource-intensive.
• Local and national programs can prioritize clinical management while reporting essential data like SAEs to aDSM systems.
• The endTB PVU model provides valuable insights into managing safety for novel TB therapeutics.