Journal Article > ResearchFull Text
Int J Tuberc Lung Dis. 2023 June 1; Volume 27 (Issue 6); 451-457.; DOI:10.5588/ijtld.22.0613
Rich ML, Khan UT, Zeng C, LaHood AN, Franke MF, et al.
Int J Tuberc Lung Dis. 2023 June 1; Volume 27 (Issue 6); 451-457.; DOI:10.5588/ijtld.22.0613
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BACKGROUND
Evidence of the effectiveness of the WHO-recommended design of longer individualized regimens for multidrug- or rifampicin-resistant TB (MDR/RR-TB) is limited.
OBJECTIVES
To report end-of-treatment outcomes for MDR/RR-TB patients from a 2015–2018 multi-country cohort that received a regimen consistent with current 2022 WHO updated recommendations and describe the complexities of comparing regimens.
METHODS
We analyzed a subset of participants from the endTB Observational Study who initiated a longer MDR/RR-TB regimen that was consistent with subsequent 2022 WHO guidance on regimen design for longer treatments. We excluded individuals who received an injectable agent or who received fewer than four likely effective drugs.
RESULTS
Of the 759 participants analyzed, 607 (80.0%, 95% CI 77.0–82.7) experienced successful end-of-treatment outcomes. The frequency of success was high across groups, whether stratified on number of Group A drugs or fluoroquinolone resistance, and ranged from 72.1% to 90.0%. Regimens were highly variable regarding composition and the duration of individual drugs.
CONCLUSIONS
Longer, all-oral, individualized regimens that were consistent with 2022 WHO guidance on regimen design had high frequencies of treatment success. Heterogeneous regimen compositions and drug durations precluded meaningful comparisons. Future research should examine which combinations of drugs maximize safety/tolerability and effectiveness.
Evidence of the effectiveness of the WHO-recommended design of longer individualized regimens for multidrug- or rifampicin-resistant TB (MDR/RR-TB) is limited.
OBJECTIVES
To report end-of-treatment outcomes for MDR/RR-TB patients from a 2015–2018 multi-country cohort that received a regimen consistent with current 2022 WHO updated recommendations and describe the complexities of comparing regimens.
METHODS
We analyzed a subset of participants from the endTB Observational Study who initiated a longer MDR/RR-TB regimen that was consistent with subsequent 2022 WHO guidance on regimen design for longer treatments. We excluded individuals who received an injectable agent or who received fewer than four likely effective drugs.
RESULTS
Of the 759 participants analyzed, 607 (80.0%, 95% CI 77.0–82.7) experienced successful end-of-treatment outcomes. The frequency of success was high across groups, whether stratified on number of Group A drugs or fluoroquinolone resistance, and ranged from 72.1% to 90.0%. Regimens were highly variable regarding composition and the duration of individual drugs.
CONCLUSIONS
Longer, all-oral, individualized regimens that were consistent with 2022 WHO guidance on regimen design had high frequencies of treatment success. Heterogeneous regimen compositions and drug durations precluded meaningful comparisons. Future research should examine which combinations of drugs maximize safety/tolerability and effectiveness.
Journal Article > ResearchFull Text
Clin Infect Dis. 2022 September 15; Volume 75 (Issue 6); 1006-1013.; DOI:10.1093/cid/ciac019
Hewison CCH, Khan UT, Bastard M, Lachenal N, Coutisson S, et al.
Clin Infect Dis. 2022 September 15; Volume 75 (Issue 6); 1006-1013.; DOI:10.1093/cid/ciac019
RATIONALE
Safety of treatment for multidrug-resistant tuberculosis (MDR/RR-TB) can be an obstacle to treatment completion.
OBJECTIVES
Evaluate safety of longer MDR/RR-TB regimens containing bedaquiline and/or delamanid.
METHODS
Multicentre (16 countries), prospective, observational study, reporting incidence and frequency of clinically relevant adverse events of special interest (AESI) amongst patients who received MDR/RR-TB treatment containing bedaquiline and/or delamanid. The AESIs were defined a priori as important events caused by bedaquiline, delamanid, linezolid, injectables, and other commonly used drugs. Occurrence of these events was also reported by exposure to the likely causative agent.
RESULTS
Among 2296 patients, the most common clinically relevant AESIs were: peripheral neuropathy in 26.4%, electrolyte depletion in 26.0%, and hearing loss in 13.2% of patients. Per 1000 person-months of treatment, the incidence of these events was 21.5 (95% confidence interval [CI]: 19.8-23.2), 20.7 (95% CI: 19.1-22.4), and 9.7 (95% CI: 8.6-10.8), respectively. QT interval was prolonged in 2.7% or 1.8 (95% CI: 1.4-2.3)/1000 person-months of treatment. Patients who received injectables (N=925) and linezolid (N=1826) were most likely to experience events during exposure: Hearing loss, acute renal failure, or electrolyte depletion occurred in 36.8% or 72.8 (95%CI: 66.0-80.0) times/1000 person-months of injectable drug exposure. Peripheral neuropathy, optic neuritis and/or myelosuppression occurred in 27.8% or 22.8 (95% CI: 20.9-24.8) times/1000 patient-months of linezolid exposure.
CONCLUSIONS
Adverse events often related to linezolid and injectable drugs were more common than those frequently attributed to bedaquiline and delamanid. MDR-TB treatment monitoring schedules and individual drug durations should reflect expected safety profiles of drug combinations.
CLINICAL TRIALS REGISTRATION
NCT02754765
Safety of treatment for multidrug-resistant tuberculosis (MDR/RR-TB) can be an obstacle to treatment completion.
OBJECTIVES
Evaluate safety of longer MDR/RR-TB regimens containing bedaquiline and/or delamanid.
METHODS
Multicentre (16 countries), prospective, observational study, reporting incidence and frequency of clinically relevant adverse events of special interest (AESI) amongst patients who received MDR/RR-TB treatment containing bedaquiline and/or delamanid. The AESIs were defined a priori as important events caused by bedaquiline, delamanid, linezolid, injectables, and other commonly used drugs. Occurrence of these events was also reported by exposure to the likely causative agent.
RESULTS
Among 2296 patients, the most common clinically relevant AESIs were: peripheral neuropathy in 26.4%, electrolyte depletion in 26.0%, and hearing loss in 13.2% of patients. Per 1000 person-months of treatment, the incidence of these events was 21.5 (95% confidence interval [CI]: 19.8-23.2), 20.7 (95% CI: 19.1-22.4), and 9.7 (95% CI: 8.6-10.8), respectively. QT interval was prolonged in 2.7% or 1.8 (95% CI: 1.4-2.3)/1000 person-months of treatment. Patients who received injectables (N=925) and linezolid (N=1826) were most likely to experience events during exposure: Hearing loss, acute renal failure, or electrolyte depletion occurred in 36.8% or 72.8 (95%CI: 66.0-80.0) times/1000 person-months of injectable drug exposure. Peripheral neuropathy, optic neuritis and/or myelosuppression occurred in 27.8% or 22.8 (95% CI: 20.9-24.8) times/1000 patient-months of linezolid exposure.
CONCLUSIONS
Adverse events often related to linezolid and injectable drugs were more common than those frequently attributed to bedaquiline and delamanid. MDR-TB treatment monitoring schedules and individual drug durations should reflect expected safety profiles of drug combinations.
CLINICAL TRIALS REGISTRATION
NCT02754765