Incidence rate and time to serious adverse events among rifampicin resistant tuberculosis patients in Georgia treated with new and repurposed anti-tuberculosis drugs, 2016-2018

Abstract

Considering the complexity of second-line anti-tuberculosis (TB) treatment regimens, the management of drug-resistant TB (DR-TB) in Georgia remains a major challenge. Since the introduction of new and repurposed anti-TB medications, the implementation of active TB Drug Safety Monitoring (aDSM) was a critical program component to help establish safety and manage all treatment related Serious Adverse Events (SAEs). In our study, we aimed to describe the occurrence, characteristics and timing of SAE among patients with Rifampicin Resistant and Multi-Drug Resistant TB (RR/MDR-TB) receiving new and/or repurposed anti-TB medications (bedaquiline, delamanid, linezolid, clofazimine, imipenem) during the period of 2016-2018 in Georgia and identify predictors of SAE. The data were obtained from the medical charts, electronic database and standardized aDSM reports During 2016-2018 period in total 970 people with RR/MDR-TB were notified in Georgia and 388 of them received new and/or repurposed TB drugs as part of their treatment regimen and all were included into the study. The results showed a total of 73 SAEs registered among 49 (12.6%) patients receiving new and/or repurposed drugs. The overall SAE incidence rate per 100 person-months was 1.16. The severity of the majority of the SAEs (46.6%) was grade III and 21.9% were grade IV. The most common SAE reported was hepatotoxicity, with an incidence of 0.26 per 100 person-month (n=16, 21.9%) followed by cardiotoxicity with an incidence of 0.16 per 100 person-month (n=10, 13.7%). Median time to SAE occurrence was 183 days (IQR 84 – 334) after treatment initiation. Resistance profile was the only predictor associated with occurrence of a SAEs. There was increased hazard of SAEs among patients with XDR-TB (adjusted HR=2.18, 95% CI: 1.12-4.23). Our findings on SAEs among patients treated with new or repurposed anti-TB drugs are echoing the findings available in the literature. They highlight the need for close monitoring of patients and underlines the importance of the aDSM during the whole treatment. Safety profile of the medications and combinations used are yet to be established and larger datasets comprised of patients receiving same treatment regimens need to be utilized.

Incidence and Predictors of Adverse Drug Events Among People Receiving Drug Resistant Tuberculosis Treatment in Uganda: 8-Year Retrospective Cohort Study

“…The reason for this difference is because our population had more people with ADE risk factors, such as HIV, aminoglycosides-based regimen and longer treatment durations, while the other study focused on newer shorter treatment regimens in predominantly HIV negative population. 20 The findings from our study could be an underestimate of the true From our study, a drug regimen containing an aminoglycoside (Am, Km, Cm) or linezolid or pyrazinamide were associated with the occurrence of an ADEs. This is consistent with findings from a systematic review that reported that ADEs leading to permanent discontinuation were associated with aminoglycosides and Lzd.…”

“…The reason for this difference is because our population had more people with ADE risk factors, such as HIV, aminoglycosides-based regimen and longer treatment durations, while the other study focused on newer shorter treatment regimens in predominantly HIV negative population. 20 The findings from our study could be an underestimate of the true value because the clinicians and patients could have under reported the ADEs during the review visits, particularly those that were mild or moderate.…”