Bedaquiline and delamanid result in low rates of unfavourable outcomes among TB patients in Eswatini

Abstract

SETTING: Since 2015, Eswatini has been scaling up bedaquiline (BDQ) and delamanid (DLM) based drug-resistant TB treatment regimens under programmatic conditions.OBJECTIVE: Identification of factors associated with treatment outcomes in patients receiving BDQ and/or DLM either as a new treatment initiation or drug substitution.DESIGN: This is a retrospective cohort study of patients receiving BDQ and/or DLM in Eswatini between March 2015 and October 2018. We describe factors associated with unfavourable treatment outcomes (death, lost to follow-up, treatment failure and amplification of resistance) and culture conversion using multivariable flexible parametric survival and competing-risks regression analyses.RESULTS: Of 352 patients receiving BDQ and/or DLM, 7.8% and 21.2% had an unfavourable treatment outcome at 6 and 24 months, respectively. Predictors were age ≥ 60 years (adjusted hazard ratio aHR 4.49, 95%CI 1.61–12.57) vs. age 20–39 years, and a treatment regimen combining both drugs (aHR 4.49, 95%CI 1.61–12.57) vs. BDQ only. The probability of culture conversion was increased for two health facilities and patients with a poly resistance profile (adjusted sub-hazard ratio 2.01, 95%CI 1.13–3.59) vs. multidrug resistance.CONCLUSION: Single use of BDQ or DLM was associated with low rates of unfavourable outcomes, suggesting that these medications may be effectively adopted at scale under routine programmatic conditions. Combined use of BDQ and DLM was a risk factor for unfavourable outcomes and should prompt for collection of more data on the combined use of these medications.

Effectiveness of the Novel Anti-TB Bedaquiline against Drug-Resistant TB in Africa: A Systematic Review of the Literature

“…These findings are in line with other bedaquiline deployment experiences from high HIV and tuberculosis burden areas [27][28][29], which reported that the early use of BDQ resulted in decreases in MDR/RR-TB-related mortality and treatment failure [6]. In addition, the included studies indicated that patients started on bedaquiline had better treatment outcomes [7,9,10,14,23].…”

“…Since the introduction of bedaquiline, limited studies in Africa have reported on the use, benefits, and challenges of this drug [25,26]. Hence, the current study aimed to conduct a situational analysis of the introduction and use of the novel drug BDQ in shorter regimens for the treatment of MDR-TB and XDR in patients with TB [8][9][10][11][12][13]21]. To our knowledge, this review contributes to the evaluation and analysis of bedaquiline introduction and usage by healthcare practitioners in Africa, as well as its successes and challenges in the treatment of MDR-TB and XDR-TB patients on the continent.…”

“…Several epidemiological studies on drug resistance, transmission dynamics, and population structure of drug-resistant TB strains have been conducted across Africa [8][9][10][11][12][13]. However, there is a scarcity of systematic data on the use of new drugs in the treatment of MDR-TB in Africa.…”

Evaluating bedaquiline as a treatment option for multidrug-resistant tuberculosis

“…The theoretical increase of side effects (especially QT prolongation), has been of concern about this combination. However, some reports suggest that this problem could have been overestimated, and the combination could be administered safely and with good efficacy [48][49][50].…”

The pipeline of new molecules and regimens against drug-resistant tuberculosis

“…In a subsequent Phase 3 study a delamanid-containing regimen did not meet the pre-specified non-inferiority criteria with regard to the median time to SCC over 6 months compared to OBR alone; however, a significant shorter time to SCC was demonstrated in sensitivity analyses and in subgroup analyses in patients without cavitation and/or fluoroquinolone resistance [43] . While global experience with delamanid remains limited, some data support its effectiveness in a multidrug background regimen [21] , [44] , [45] , [46] . Ongoing clinical trials evaluate delamanid in various oral regimens of 6–12 months duration in rifampicin-resistant (RR), MDR and FQ-resistant TB, some also in combination with bedaquiline (endTB – Table 1 ) and will provide a better understanding of its role in current MDR TB management.…”