A prospective patient registry to monitor safety, effectiveness, and utilisation of bedaquiline in patients with multidrug-resistant tuberculosis in South Korea

Abstract

Background Multidrug-resistant tuberculosis (MDR-TB) represents a major public health concern, with an ongoing need for new effective treatments. Bedaquiline is an oral diarylquinoline that has shown encouraging treatment success and culture conversion rates in MDR-TB. Methods A South Korean patient registry was set up across 19 centres between 2016 and 2018 for the prospective collection of data from patients with MDR-TB who received either a bedaquiline-containing or a non-bedaquiline-containing regimen. Treatment was at the physician’s discretion (bedaquiline use requiring approval by special committee) and was based on patient characteristics, disease status, and local treatment guidelines. Results The safety population included 172 patients (88 bedaquiline and 84 non-bedaquiline). The mean (standard deviation, SD) duration of follow-up was 24.3 (9.5) months. Mean (SD) durations of treatment were 5.4 (1.8) months in bedaquiline-treated patients and 15.7 (6.7) months in the non-bedaquiline group. Treatment success (cured and treatment completed according to WHO 2013 treatment outcome definitions) was achieved by 56.3% of bedaquiline-treated and 45.2% of non-bedaquiline-treated patients. Sputum culture conversion rates were 90.4% and 83.7% with and without bedaquiline, respectively. Diarrhoea and nausea were the most frequently reported treatment-emergent adverse events (TEAEs) in the bedaquiline group (27.3% [24/88] and 22.7% [20/88], respectively). The most frequent bedaquiline-related TEAEs were prolonged QT interval (10.2%; 9/88), and diarrhoea and nausea (9.1% each; 8/88). QT interval prolongation was reported in 19.3% (17/88) of bedaquiline-treated and 2.4% (2/84) of non-bedaquiline-treated patients, but bedaquiline was not discontinued for any patient for this reason. There were 13 (14.7%) and three (3.6%) deaths in the bedaquiline-treated and non-bedaquiline groups, respectively. Review of fatal cases revealed no unexpected safety findings, and no deaths were bedaquiline-related. The most common cause of death was worsening cancer (three patients). Patients in the bedaquiline group tended to have poorer baseline risk profiles than non-bedaquiline patients and were more likely to have relapsed or already failed second-line treatment. Interpretation of mortality data was complicated by high rates of loss to follow-up in both groups. Conclusions The South Korean registry findings support previous risk/benefit observations and the continued use of bedaquiline as part of combination therapy in patients with MDR-TB.

The Effectiveness and Safety of Bedaquiline-Containing Regimens in the Treatment of Patients With Multi-Drug Resistant Tuberculosis (Mdr-Tb): A Systematic Literature Review

“…In the study by [7], the maximum change from baseline in the Bdq group was 72 ms at week 18, although no Grade 3 or 4 QTc prolongation events were observed, and no deaths occurred during the study treatment [7]. In the study by [13], the most common side effects associated with bedaquiline were QT interval prolongation (10.2%), diarrhea, and nausea (9.1%), but no deaths were linked to bedaquiline use [13]. In the study by [9] involving 277 MDR-TB patients, 77 (39%) received BDQ, with a total of 8 serious adverse effects, including 5 (6.5%) deaths, where 1 (1.3%) QTcF prolongation of Grade 3 was attributed to bedaquiline [9].…”

“…Similar results were observed in other studies. In the study by [13] in South Korea, among 172 MDR-TB patients, the sputum conversion rate in the bedaquiline-treated group was 90.4% [13]. [14] in East China showed a sputum culture conversion rate of 89.2% at month 3, 91.2% at month 9, and 94.1% at month 12 in the bedaquiline group, all significantly higher compared to the SLI group (p < 0.001) [14].…”

“…Treatment success, defined as a combination of patients cured and treatment completed according to the WHO 2013 treatment outcome definition, as well as deaths during treatment in the group containing a bedaquiline regimen, demonstrated better outcomes compared to those without bedaquiline. In the study by [13], treatment success was achieved in 56.3% of patients treated with bedaquiline and 45.2% of patients without bedaquiline, with a death rate of 14.9% [13]. In the studies by [11] and [8], treatment success rates were 66.9% and 74%, respectively, with death rates of 15% and 17% in the groups treated with bedaquiline-containing regimens.…”

“…[12] and [14] reported average conversion times of 2 months and 3 months, respectively [12] [14]. Other studies reported average conversion times ranging from 39 days to 102 days [13] [11]. Treatment success, defined as a combination of patients cured and treatment completed according to the WHO 2013 treatment outcome definition, as well as deaths during treatment in the group containing a bedaquiline regimen, demonstrated better outcomes compared to those without bedaquiline.…”

Efficacy and safety of bedaquiline containing regimens in patients of drug-resistant tuberculosis: An updated systematic review and meta-analysis

“…In total, 41 studies are included in the updated version of this review. The studies [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [40] , [41] , [42] , [43] , [44] , [45] , [46] , [47] , [48] , [49] , [50] , [51] , [52] , [53] , [54] , [55] , [56] , [57] , [58] , [59] , [60] , [61] , [62] , [63] , [64] , [65] , [66] , [67] , [68] , [69] were divided into two groups: 36 observational studies including a total of 9,934 patients, and 5 experimental studies including a total of 468 patients. The patient’s mean age was 36.2 years.…”