Journal Article > ResearchFull Text
Lancet Global Health. 1 February 2025; Volume 13 (Issue 2); e355-e363.; DOI:10.1016/S2214-109X(24)00467-4
Sweeney S, Laurence YV, Berry C, Singh MP, Dodd M, et al.
Lancet Global Health. 1 February 2025; Volume 13 (Issue 2); e355-e363.; DOI:10.1016/S2214-109X(24)00467-4
BACKGROUND
New 6-month rifampicin-resistant tuberculosis treatment regimens containing bedaquiline, pretomanid, and linezolid (BPaL) with or without moxifloxacin or clofazimine, could improve treatment efficacy, safety, and tolerability, and free up resources within the health system. Following a change to WHO rifampicin-resistant tuberculosis treatment guidelines, countries are facing difficult decisions about when and how to incorporate new drug regimens into national guidelines. We aimed to assess the probability of BPaL-based regimens being cost-saving using data collected in the TB-PRACTECAL trial.
METHODS
This economic evaluation using a cost-utility analysis was embedded in five TB-PRACTECAL trial sites in Belarus, Uzbekistan, and South Africa. Between Nov 19, 2020, and Sept 27, 2022, we collected detailed primary unit cost data in six hospitals and four ambulatory health facilities and collected data on patient-incurred costs from 73 trial participants. The primary efficacy endpoint of the main trial, a composite of unfavourable outcomes (death, disease recurrence, treatment failure, early discontinuation of therapy, withdrawal, or loss to follow-up) and clinically important safety outcomes by 72 weeks of follow-up were incorporated into the analysis. Societal perspective cost data and effect outcome data were input into a Markov model to estimate the cost per disability-adjusted life-year (DALY) averted by BPaL-based regimens compared with the standard of care over a 20-year time horizon. We conducted a range of univariate and probabilistic sensitivity analyses to test our findings.
FINDINGS
BPaL-based regimens averted a mean of 1·28 DALYs and saved a mean of US$14 868 (SD 291) per person from the provider perspective compared with standard-of-care regimens over 20 years. Patient-incurred costs were reduced by a mean of $172 (SD 0·84) in BPaL-based regimen groups compared with standard of care. The main cost drivers for both providers and patients were inpatient bed-days; the duration of the inpatient period varied across countries. Varying a range of model parameters affected the degree of cost savings but did not change the finding that BPaL-based regimens are cost-saving compared with standard of care.
INTERPRETATION
This trial-based evidence adds to consistent indications from modelling studies that BPaL-based regimens are cost-saving for both the patient and health system. Urgent implementation of BPaL-based regimens in countries with a high burden of tuberculosis could improve treatment of rifampicin-resistant tuberculosis, reduce pill burden, and free up desperately needed resources within the health system.
Journal Article > ResearchFull Text
Antimicrob Agents Chemother. 6 June 2024; Volume 68 (Issue 7); e0053624.; DOI:10.1128/aac.00536-24
Motta I, Cusinato M, Ludman AJ, Lachenal N, Dodd M, et al.
Antimicrob Agents Chemother. 6 June 2024; Volume 68 (Issue 7); e0053624.; DOI:10.1128/aac.00536-24
Regimens for the treatment of rifampicin-resistant tuberculosis currently rely on the use of QT-prolonging agents. Using data from the randomized controlled trial, TB-PRACTECAL, we investigated differences in QTcF among participants in the three interventional arms: BPaL (bedaquiline, pretomanid, and linezolid), BPaLC (BPaL with clofazimine), and BPaLM (BPaL with moxifloxacin). Additionally, we assessed whether age, body mass index, and country were causally associated with QTcF prolongation. The trial included participants from South Africa, Uzbekistan, and Belarus. A post hoc analysis of electrocardiogram data was undertaken. Random effects regression was used to model QTcF longitudinally over 24 weeks and causal frameworks guided the analysis of non-randomized independent variables. 328 participants were included in BPaL-based arms. The longitudinal analysis of investigational arms showed an initial QTcF steep increase in the first week. QTcF trajectories between weeks 2 and 24 differed slightly by regimen, with highest mean peak for BPaLC (QTcF 446.5 ms). Overall, there were 397 QTcF >450 ms (of 3,744) and only one QTcF >500 ms. The odds of QTcF >450 ms among participants in any investigational arm, was 8.33 times higher in Uzbekistan compared to Belarus (95% confidence interval: 3.25–21.33). No effect on QTcF prolongation was found for baseline age or body mass index (BMI). Clinically significant QTc prolongation was rare in this cohort of closely monitored participants. Across BPaL-based regimens, BPaLC showed a slightly longer and sustained effect on QTcF prolongation, but the differences (both in magnitude of change and trajectory over time) were clinically unimportant. The disparity in the risk of QTc prolongation across countries would be an important factor to further investigate when evaluating monitoring strategies.
Journal Article > ReviewFull Text
Clin Infect Dis. 20 March 2024; Volume 78 (Issue 3); 730-741.; DOI:10.1093/cid/ciad653
Hasan T, Medcalf E, Nyang'wa BT, Egizi E, Berry C, et al.
Clin Infect Dis. 20 March 2024; Volume 78 (Issue 3); 730-741.; DOI:10.1093/cid/ciad653
BACKGROUND
Effectiveness, safety, tolerability, and adherence are critical considerations in shifting to shorter tuberculosis (TB) regimens. Novel 6-month oral regimens that include bedaquiline (B), pretomanid (Pa), and linezolid (L), with or without a fourth drug, have been shown to be as or more effective than the established longer regimens for the treatment of multidrug-resistant/rifampicin-resistant TB (MDR/RR-TB). We aimed to evaluate the safety and tolerability of linezolid in BPaL-containing regimens for the treatment of MDR/RR-TB among recently completed clinical trials.
METHODS
A review and meta-analysis was undertaken including published and unpublished data from clinical trials, conducted between 2010 and 2021, that evaluated regimens containing BPaL for the treatment of MDR/RR-TB. Individual patient data were obtained. For each BPaL-containing regimen, we evaluated the frequency and severity of treatment-related adverse events. The risk difference of adverse events for each regimen was calculated, in comparison to patients assigned to receiving the lowest cumulative exposure of linezolid.
RESULTS
Data from 3 clinical trials investigating 8 unique BPaL-containing regimens were included, comprising a total of 591 participants. Adverse events were more frequent in groups randomized to a higher cumulative linezolid dose. Among patients who were randomized to a daily dose of 1200 mg linezolid, 68 of 195 (35%) experienced a grade 3–4 adverse event versus 89 of 396 (22%) patients receiving BPaL-containing regimens containing 600 mg linezolid.
CONCLUSIONS
Regimens containing BPaL were relatively well tolerated when they included a daily linezolid dose of 600 mg. These novel regimens promise to improve the tolerability of treatment for MDR/RR-TB.
Effectiveness, safety, tolerability, and adherence are critical considerations in shifting to shorter tuberculosis (TB) regimens. Novel 6-month oral regimens that include bedaquiline (B), pretomanid (Pa), and linezolid (L), with or without a fourth drug, have been shown to be as or more effective than the established longer regimens for the treatment of multidrug-resistant/rifampicin-resistant TB (MDR/RR-TB). We aimed to evaluate the safety and tolerability of linezolid in BPaL-containing regimens for the treatment of MDR/RR-TB among recently completed clinical trials.
METHODS
A review and meta-analysis was undertaken including published and unpublished data from clinical trials, conducted between 2010 and 2021, that evaluated regimens containing BPaL for the treatment of MDR/RR-TB. Individual patient data were obtained. For each BPaL-containing regimen, we evaluated the frequency and severity of treatment-related adverse events. The risk difference of adverse events for each regimen was calculated, in comparison to patients assigned to receiving the lowest cumulative exposure of linezolid.
RESULTS
Data from 3 clinical trials investigating 8 unique BPaL-containing regimens were included, comprising a total of 591 participants. Adverse events were more frequent in groups randomized to a higher cumulative linezolid dose. Among patients who were randomized to a daily dose of 1200 mg linezolid, 68 of 195 (35%) experienced a grade 3–4 adverse event versus 89 of 396 (22%) patients receiving BPaL-containing regimens containing 600 mg linezolid.
CONCLUSIONS
Regimens containing BPaL were relatively well tolerated when they included a daily linezolid dose of 600 mg. These novel regimens promise to improve the tolerability of treatment for MDR/RR-TB.
Journal Article > ResearchFull Text
Lancet Respir Med. 1 February 2024; Volume 12 (Issue 2); 117-128.; DOI:10.1016/S2213-2600(23)00389-2
Nyang'wa BT, Berry C, Kazounis E, Motta I, Parpieva N, et al.
Lancet Respir Med. 1 February 2024; Volume 12 (Issue 2); 117-128.; DOI:10.1016/S2213-2600(23)00389-2
BACKGROUND
Around 500,000 people worldwide develop rifampicin-resistant tuberculosis each year. The proportion of successful treatment outcomes remains low and new treatments are needed. Following an interim analysis, we report the final safety and efficacy outcomes of the TB-PRACTECAL trial, evaluating the safety and efficacy of oral regimens for the treatment of rifampicin-resistant tuberculosis.
METHODS
This open-label, randomised, controlled, multi-arm, multicentre, non-inferiority trial was conducted at seven hospital and community sites in Uzbekistan, Belarus, and South Africa, and enrolled participants aged 15 years and older with pulmonary rifampicin-resistant tuberculosis. Participants were randomly assigned, in a 1:1:1:1 ratio using variable block randomisation and stratified by trial site, to receive 36-80 week standard care; 24-week oral bedaquiline, pretomanid, and linezolid (BPaL); BPaL plus clofazimine (BPaLC); or BPaL plus moxifloxacin (BPaLM) in stage one of the trial, and in a 1:1 ratio to receive standard care or BPaLM in stage two of the trial, the results of which are described here. Laboratory staff and trial sponsors were masked to group assignment and outcomes were assessed by unmasked investigators. The primary outcome was the percentage of participants with a composite unfavourable outcome (treatment failure, death, treatment discontinuation, disease recurrence, or loss to follow-up) at 72 weeks after randomisation in the modified intention-to-treat population (all participants with rifampicin-resistant disease who received at least one dose of study medication) and the per-protocol population (a subset of the modified intention-to-treat population excluding participants who did not complete a protocol-adherent course of treatment (other than because of treatment failure or death) and those who discontinued treatment early because they violated at least one of the inclusion or exclusion criteria). Safety was measured in the safety population. The non-inferiority margin was 12%. This trial is registered with ClinicalTrials.gov, NCT02589782, and is complete.
FINDINGS
Between Jan 16, 2017, and March 18, 2021, 680 patients were screened for eligibility, of whom 552 were enrolled and randomly assigned (152 to the standard care group, 151 to the BPaLM group, 126 to the BPaLC group, and 123 to the BPaL group). The standard care and BPaLM groups proceeded to stage two and are reported here, post-hoc analyses of the BPaLC and BPaL groups are also reported. 151 participants in the BPaLM group and 151 in the standard care group were included in the safety population, with 138 in the BPaLM group and 137 in the standard care group in the modified intention-to-treat population. In the modified intention-to-treat population, unfavourable outcomes were reported in 16 (12%) of 137 participants for whom outcome was assessable in the BPaLM group and 56 (41%) of 137 participants in the standard care group (risk difference -29·2 percentage points [96·6% CI -39·8 to -18·6]; non-inferiority and superiority p<0·0001). 34 (23%) of 151 participants receiving BPaLM had adverse events of grade 3 or higher or serious adverse events, compared with 72 (48%) of 151 participants receiving standard care (risk difference -25·2 percentage points [96·6% CI -36·4 to -13·9]). Five deaths were reported in the standard care group by week 72, of which one (COVID-19 pneumonia) was unrelated to treatment and four (acute pancreatitis, suicide, sudden death, and sudden cardiac death) were judged to be treatment-related.
INTERPRETATION
The 24-week, all-oral BPaLM regimen is safe and efficacious for the treatment of pulmonary rifampicin-resistant tuberculosis, and was added to the WHO guidance for treatment of this condition in 2022. These findings will be key to BPaLM becoming the preferred regimen for adolescents and adults with pulmonary rifampicin-resistant tuberculosis.
Around 500,000 people worldwide develop rifampicin-resistant tuberculosis each year. The proportion of successful treatment outcomes remains low and new treatments are needed. Following an interim analysis, we report the final safety and efficacy outcomes of the TB-PRACTECAL trial, evaluating the safety and efficacy of oral regimens for the treatment of rifampicin-resistant tuberculosis.
METHODS
This open-label, randomised, controlled, multi-arm, multicentre, non-inferiority trial was conducted at seven hospital and community sites in Uzbekistan, Belarus, and South Africa, and enrolled participants aged 15 years and older with pulmonary rifampicin-resistant tuberculosis. Participants were randomly assigned, in a 1:1:1:1 ratio using variable block randomisation and stratified by trial site, to receive 36-80 week standard care; 24-week oral bedaquiline, pretomanid, and linezolid (BPaL); BPaL plus clofazimine (BPaLC); or BPaL plus moxifloxacin (BPaLM) in stage one of the trial, and in a 1:1 ratio to receive standard care or BPaLM in stage two of the trial, the results of which are described here. Laboratory staff and trial sponsors were masked to group assignment and outcomes were assessed by unmasked investigators. The primary outcome was the percentage of participants with a composite unfavourable outcome (treatment failure, death, treatment discontinuation, disease recurrence, or loss to follow-up) at 72 weeks after randomisation in the modified intention-to-treat population (all participants with rifampicin-resistant disease who received at least one dose of study medication) and the per-protocol population (a subset of the modified intention-to-treat population excluding participants who did not complete a protocol-adherent course of treatment (other than because of treatment failure or death) and those who discontinued treatment early because they violated at least one of the inclusion or exclusion criteria). Safety was measured in the safety population. The non-inferiority margin was 12%. This trial is registered with ClinicalTrials.gov, NCT02589782, and is complete.
FINDINGS
Between Jan 16, 2017, and March 18, 2021, 680 patients were screened for eligibility, of whom 552 were enrolled and randomly assigned (152 to the standard care group, 151 to the BPaLM group, 126 to the BPaLC group, and 123 to the BPaL group). The standard care and BPaLM groups proceeded to stage two and are reported here, post-hoc analyses of the BPaLC and BPaL groups are also reported. 151 participants in the BPaLM group and 151 in the standard care group were included in the safety population, with 138 in the BPaLM group and 137 in the standard care group in the modified intention-to-treat population. In the modified intention-to-treat population, unfavourable outcomes were reported in 16 (12%) of 137 participants for whom outcome was assessable in the BPaLM group and 56 (41%) of 137 participants in the standard care group (risk difference -29·2 percentage points [96·6% CI -39·8 to -18·6]; non-inferiority and superiority p<0·0001). 34 (23%) of 151 participants receiving BPaLM had adverse events of grade 3 or higher or serious adverse events, compared with 72 (48%) of 151 participants receiving standard care (risk difference -25·2 percentage points [96·6% CI -36·4 to -13·9]). Five deaths were reported in the standard care group by week 72, of which one (COVID-19 pneumonia) was unrelated to treatment and four (acute pancreatitis, suicide, sudden death, and sudden cardiac death) were judged to be treatment-related.
INTERPRETATION
The 24-week, all-oral BPaLM regimen is safe and efficacious for the treatment of pulmonary rifampicin-resistant tuberculosis, and was added to the WHO guidance for treatment of this condition in 2022. These findings will be key to BPaLM becoming the preferred regimen for adolescents and adults with pulmonary rifampicin-resistant tuberculosis.
Journal Article > ResearchFull Text
Clin Infect Dis. 24 October 2023; Online ahead of print; ciad653.; DOI:10.1093/cid/ciad653
Hasan T, Medcalf E, Nyang'wa BT, Egizi E, Berry C, et al.
Clin Infect Dis. 24 October 2023; Online ahead of print; ciad653.; DOI:10.1093/cid/ciad653
BACKGROUND
Effectiveness, safety, tolerability and adherence are critical considerations in shifting to shorter tuberculosis (TB) regimens. Novel six-month oral regimens that include bedaquiline (B), pretomanid (Pa), linezolid (L) with or without a fourth drug, have been shown to be as or more effective than the established longer regimens for the treatment of multi-drug resistant tuberculosis/rifampicin resistant (MDR/RR-TB). We aimed to evaluate the safety and tolerability of linezolid in BPaL-containing regimens for the treatment of MDR/RR-TB among recently-completed clinical trials.
METHODS
A review and meta-analysis was undertaken including published and unpublished data from clinical trials, conducted between 2010 and 2021, that evaluated regimens containing BPaL for the treatment of MDR/RR-TB. Individual patient data were obtained. For each BPaL-containing regimen, we evaluated the frequency and severity of treatment related adverse events. The risk difference of adverse events for each regimen was calculated, in comparison to patients assigned to receiving the lowest cumulative exposure of linezolid.
RESULTS
Data from three clinical trials investigating eight unique BPaL-containing regimens were included, comprising a total of 591 participants. Adverse events were more frequent in groups randomized to a higher cumulative linezolid dose. Among patients who were randomized to a daily dose of 1200mg of linezolid, 68/195 (35%) experienced a Grade 3-4 adverse event vs 89/396 (22%) of patients receiving BPaL-containing regimens containing 600mg of linezolid.
CONCLUSIONS
Regimens containing BPaL were relatively well-tolerated when they included a daily linezolid dose of 600mg. These novel regimens promise to improve the tolerability of treatment for MDR/RR-TB.
Effectiveness, safety, tolerability and adherence are critical considerations in shifting to shorter tuberculosis (TB) regimens. Novel six-month oral regimens that include bedaquiline (B), pretomanid (Pa), linezolid (L) with or without a fourth drug, have been shown to be as or more effective than the established longer regimens for the treatment of multi-drug resistant tuberculosis/rifampicin resistant (MDR/RR-TB). We aimed to evaluate the safety and tolerability of linezolid in BPaL-containing regimens for the treatment of MDR/RR-TB among recently-completed clinical trials.
METHODS
A review and meta-analysis was undertaken including published and unpublished data from clinical trials, conducted between 2010 and 2021, that evaluated regimens containing BPaL for the treatment of MDR/RR-TB. Individual patient data were obtained. For each BPaL-containing regimen, we evaluated the frequency and severity of treatment related adverse events. The risk difference of adverse events for each regimen was calculated, in comparison to patients assigned to receiving the lowest cumulative exposure of linezolid.
RESULTS
Data from three clinical trials investigating eight unique BPaL-containing regimens were included, comprising a total of 591 participants. Adverse events were more frequent in groups randomized to a higher cumulative linezolid dose. Among patients who were randomized to a daily dose of 1200mg of linezolid, 68/195 (35%) experienced a Grade 3-4 adverse event vs 89/396 (22%) of patients receiving BPaL-containing regimens containing 600mg of linezolid.
CONCLUSIONS
Regimens containing BPaL were relatively well-tolerated when they included a daily linezolid dose of 600mg. These novel regimens promise to improve the tolerability of treatment for MDR/RR-TB.
Journal Article > ResearchFull Text
N Engl J Med. 22 December 2022; Volume 387 (Issue 25); 2331-2343.; DOI:10.1056/NEJMoa2117166
Nyang'wa BT, Berry C, Kazounis E, Motta I, Parpieva N, et al.
N Engl J Med. 22 December 2022; Volume 387 (Issue 25); 2331-2343.; DOI:10.1056/NEJMoa2117166
BACKGROUND
In patients with rifampin-resistant tuberculosis, all-oral treatment regimens that are more effective, shorter, and have a more acceptable side-effect profile than current regimens are needed.
METHODS
We conducted an open-label, phase 2–3, multicenter, randomized, controlled, noninferiority trial to evaluate the efficacy and safety of three 24-week, all-oral regimens for the treatment of rifampin-resistant tuberculosis. Patients in Belarus, South Africa, and Uzbekistan who were 15 years of age or older and had rifampin-resistant pulmonary tuberculosis were enrolled. In stage 2 of the trial, a 24-week regimen of bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM) was compared with a 9-to-20-month standard-care regimen. The primary outcome was an unfavorable status (a composite of death, treatment failure, treatment discontinuation, loss to follow-up, or recurrence of tuberculosis) at 72 weeks after randomization. The noninferiority margin was 12 percentage points.
RESULTS
Recruitment was terminated early. Of 301 patients in stage 2 of the trial, 145, 128, and 90 patients were evaluable in the intention-to-treat, modified intention-to-treat, and per-protocol populations, respectively. In the modified intention-to-treat analysis, 11% of the patients in the BPaLM group and 48% of those in the standard-care group had a primary-outcome event (risk difference, -37 percentage points; 96.6% confidence interval [CI], -53 to -22). In the per-protocol analysis, 4% of the patients in the BPaLM group and 12% of those in the standard-care group had a primary-outcome event (risk difference, -9 percentage points; 96.6% CI, -22 to 4). In the as-treated population, the incidence of adverse events of grade 3 or higher or serious adverse events was lower in the BPaLM group than in the standard-care group (19% vs. 59%).
CONCLUSIONS
In patients with rifampin-resistant pulmonary tuberculosis, a 24-week, all-oral regimen was noninferior to the accepted standard-care treatment, and it had a better safety profile. (Funded by Médecins sans Frontières; TB-PRACTECAL ClinicalTrials.gov number, NCT02589782. opens in new tab.)
In patients with rifampin-resistant tuberculosis, all-oral treatment regimens that are more effective, shorter, and have a more acceptable side-effect profile than current regimens are needed.
METHODS
We conducted an open-label, phase 2–3, multicenter, randomized, controlled, noninferiority trial to evaluate the efficacy and safety of three 24-week, all-oral regimens for the treatment of rifampin-resistant tuberculosis. Patients in Belarus, South Africa, and Uzbekistan who were 15 years of age or older and had rifampin-resistant pulmonary tuberculosis were enrolled. In stage 2 of the trial, a 24-week regimen of bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM) was compared with a 9-to-20-month standard-care regimen. The primary outcome was an unfavorable status (a composite of death, treatment failure, treatment discontinuation, loss to follow-up, or recurrence of tuberculosis) at 72 weeks after randomization. The noninferiority margin was 12 percentage points.
RESULTS
Recruitment was terminated early. Of 301 patients in stage 2 of the trial, 145, 128, and 90 patients were evaluable in the intention-to-treat, modified intention-to-treat, and per-protocol populations, respectively. In the modified intention-to-treat analysis, 11% of the patients in the BPaLM group and 48% of those in the standard-care group had a primary-outcome event (risk difference, -37 percentage points; 96.6% confidence interval [CI], -53 to -22). In the per-protocol analysis, 4% of the patients in the BPaLM group and 12% of those in the standard-care group had a primary-outcome event (risk difference, -9 percentage points; 96.6% CI, -22 to 4). In the as-treated population, the incidence of adverse events of grade 3 or higher or serious adverse events was lower in the BPaLM group than in the standard-care group (19% vs. 59%).
CONCLUSIONS
In patients with rifampin-resistant pulmonary tuberculosis, a 24-week, all-oral regimen was noninferior to the accepted standard-care treatment, and it had a better safety profile. (Funded by Médecins sans Frontières; TB-PRACTECAL ClinicalTrials.gov number, NCT02589782. opens in new tab.)
Journal Article > ResearchFull Text
PLOS Glob Public Health. 7 December 2022; Volume 2 (Issue 12); e0001337.; DOI:10.1371/journal.pgph.0001337
Sweeney S, Berry C, Kazounis E, Motta I, Vassall A, et al.
PLOS Glob Public Health. 7 December 2022; Volume 2 (Issue 12); e0001337.; DOI:10.1371/journal.pgph.0001337
Current options for treating tuberculosis (TB) that is resistant to rifampicin (RR-TB) are few, and regimens are often long and poorly tolerated. Following recent evidence from the TB-PRACTECAL trial countries are considering programmatic uptake of 6-month, all-oral treatment regimens. We used a Markov model to estimate the incremental cost-effectiveness of three regimens containing bedaquiline, pretomanid and linezolid (BPaL) with and without moxifloxacin (BPaLM) or clofazimine (BPaLC) compared with the current mix of long and short standard of care (SOC) regimens to treat RR-TB from the provider perspective in India, Georgia, Philippines, and South Africa. We estimated total costs (2019 USD) and disability-adjusted life years (DALYs) over a 20-year time horizon. Costs and DALYs were discounted at 3% in the base case. Parameter uncertainty was tested with univariate and probabilistic sensitivity analysis. We found that all three regimens would improve health outcomes and reduce costs compared with the current programmatic mix of long and short SOC regimens in all four countries. BPaL was the most cost-saving regimen in all countries, saving $112-$1,173 per person. BPaLM was the preferred regimen at a willingness to pay per DALY of 0.5 GDP per capita in all settings. Our findings indicate BPaL-based regimens are likely to be cost-saving and more effective than the current standard of care in a range of settings. Countries should consider programmatic uptake of BPaL-based regimens.
Journal Article > Pre-Print
medRxiv. 10 November 2022; DOI:10.1101/2022.11.08.22282060
Sweeney S, Berry C, Kazounis E, Motta I, Vassall A, et al.
medRxiv. 10 November 2022; DOI:10.1101/2022.11.08.22282060
INTRODUCTION
Current options for treating tuberculosis (TB) that is resistant to rifampicin (RR-TB) are few, and regimens are often long and poorly tolerated. Following recent evidence from the TB-PRACTECAL trial countries are considering programmatic uptake of 6-month, all-oral treatment regimens.
METHODS
We used a Markov model to estimate the incremental cost-effectiveness of three regimens containing bedaquiline, pretomanid and linezolid (BPaL) with and without moxifloxacin (BPaLM) or clofazimine (BPaLC) compared with the current mix of long and short standard of care (SOC) regimens to treat RR-TB from the provider perspective in India, Georgia, Philippines, and South Africa. We estimated total costs (2019 USD) and disability-adjusted life years (DALYs) over a 20-year time horizon. Costs and DALYs were discounted at 3% in the base case. Parameter uncertainty was tested with univariate and probabilistic sensitivity analysis.
RESULTS
We found that all three regimens would improve health outcomes and reduce costs compared with the current programmatic mix of long and short SOC regimens in all four countries. BPaL was the most cost-saving regimen in all countries, saving $112-$1,173 per person. BPaLM was the preferred regimen at a willingness to pay per DALY of 0.5 GDP per capita in all settings.
CONCLUSIONS
Our findings indicate BPaL-based regimens are likely to be cost-saving and more effective than the current standard of care in a range of settings. Countries should consider programmatic uptake of BPaL-based regimens.
Current options for treating tuberculosis (TB) that is resistant to rifampicin (RR-TB) are few, and regimens are often long and poorly tolerated. Following recent evidence from the TB-PRACTECAL trial countries are considering programmatic uptake of 6-month, all-oral treatment regimens.
METHODS
We used a Markov model to estimate the incremental cost-effectiveness of three regimens containing bedaquiline, pretomanid and linezolid (BPaL) with and without moxifloxacin (BPaLM) or clofazimine (BPaLC) compared with the current mix of long and short standard of care (SOC) regimens to treat RR-TB from the provider perspective in India, Georgia, Philippines, and South Africa. We estimated total costs (2019 USD) and disability-adjusted life years (DALYs) over a 20-year time horizon. Costs and DALYs were discounted at 3% in the base case. Parameter uncertainty was tested with univariate and probabilistic sensitivity analysis.
RESULTS
We found that all three regimens would improve health outcomes and reduce costs compared with the current programmatic mix of long and short SOC regimens in all four countries. BPaL was the most cost-saving regimen in all countries, saving $112-$1,173 per person. BPaLM was the preferred regimen at a willingness to pay per DALY of 0.5 GDP per capita in all settings.
CONCLUSIONS
Our findings indicate BPaL-based regimens are likely to be cost-saving and more effective than the current standard of care in a range of settings. Countries should consider programmatic uptake of BPaL-based regimens.
Conference Material > Slide Presentation
Berry C, Motta I, Kazounis E, Fielding K, Dodd M, et al.
MSF Scientific Days International 2022. 11 May 2022; DOI:10.57740/v9ye-0032
Conference Material > Video
Berry C, Motta I, Kazounis E, Fielding K, Dodd M, et al.
MSF Scientific Days International 2022. 7 June 2022; DOI:10.57740/atfr-ws57