Comparative effectiveness of individualized longer and standardized shorter regimens in the treatment of multidrug resistant tuberculosis in a high burden country

Abstract

Objective: To compare the effectiveness of second line injectables containing shorter (duration 9–12 months) and longer treatment regimens (LTR, duration ≥ 20 months) among multidrug-resistant tuberculosis (MDR-TB) patients with no documented resistance and history of treatment with any second-line anti-TB drug (SLD) for ≥ 1 month.Methods: This was an observational cohort study of MDR-TB patients treated at eight PMDT units in Pakistan. Patients’ data from baseline until treatment outcomes were collected from Electronic Nominal Recording and Reporting System. The treatment outcomes of “cured” and “treatment completed” were grouped together as successful, whereas “death,” “treatment failure,” and “lost to follow-up” were collectively grouped as unsuccessful outcomes. Time to sputum culture conversion (SCC) was analyzed using the Kaplan–Meier method and the differences between groups were compared through the log-rank test. Multivariate Cox proportional hazards and binary logistic regression analyses were used to find predictors of time to SCC and unsuccessful treatment outcomes. A p-value < 0.05 was considered statistically significant.Results: A total 701 eligible MDR-TB patients [313 treated with shorter treatment regimen (STR) and 388 treated with LTR at eight centres in Pakistan were evaluated]. Time to achieve SCC was significantly shorter in STR group [mean: 2.03 months, 95% confidence interval (CI):1.79–2.26] than in LTR group (mean: 2.69 months, 95% CI: 2.35–3.03) (p-value<0.001, Log-rank test). Treatment success was higher in STR (83.7%) than in LTR (73.2%) group (p-value <0.001) due to high cure (79.9% vs. 70.9%, p-value = 0.006) and low death (9.9% vs. 18.3%, p-value = 0.002) rates with STR. Treatment with STR emerged the only predictor of early SCC [adjusted Hazards ratio (aHR) = 0.815, p-value = 0.014], whereas, patient’s age of 41–60 (OR = 2.62, p-value<0.001) and >60 years (OR = 5.84, p-value<0.001), baseline body weight of 31–60 (OR = 0.36, p-value = 0.001) and >60 kg (OR = 0.23, p-value <0.001), and treatment with LTR (OR = 1.88, p-value = 0.001) had statistically significant association with unsuccessful treatment outcomes.Conclusion: STR exhibited superior anti-microbial activity against MDR-TB. When compared LTR, treatment with STR resulted in significantly early SCC, high cure, and lower death rates among MDR-TB patients who had no documented resistance and history of treatment with any SLD ≥ 1 month.

Frequency, management and impact of adverse events on treatment outcomes in patients with multidrug resistant tuberculosis in Balochistan, Pakistan

“…In our present cohort, the treatment success rate was found to be 67.6%, which fell within the range reported by studies conducted at other PMDT units in Pakistan (40.5-75.2%) (N Ahmad et al, 2015 ; Atif et al, 2020 ; Atif et al, 2017 ; Javaid et al, 2018 ; Javaid, Shaheen, et al, 2017 ; Khan et al, 2019 ; Abdul Wahid et al, 2022 ). Notably, the incidence of unsuccessful treatment outcomes was significantly higher in patients aged >40 years, those with a baseline body weight ≤30 kg and who were residents of rural areas.…”

“…At these centres, MDR-TB patients receive care according to uniform protocols recommended by the World Health Organization (WHO) and adopted by the National TB Control Program (NTP) (Abubakar, Ahmad, Atif, Khan, & Ghafoor, 2022 ; Javaid et al, 2018 ; Khan et al, 2019 ; Naz et al, 2021 ). While there is significant information available from Pakistan regarding the treatment outcomes and predictors of unsuccessful outcomes among MDR-TB patients (Abubakar et al, 2021 ; N Ahmad et al, 2015 ; Atif et al, 2017 ; Javaid et al, 2018 ; Javaid, Shaheen, et al, 2017 ; Khan et al, 2019 ; Naz et al, 2021 ; Abdul Wahid et al, 2022 ), there is scarcity of detailed information regarding the occurrence and management of AEs during MDR-TB treatment as well as their impact on treatment outcomes (Atif et al, 2022 ; Massud et al, 2022 ) from Pakistan in general and Balochistan in particular, which is the largest province in Pakistan in terms of area. Since early detection, monitoring, and appropriate management of AEs are crucial for optimising MDR-TB treatment, therefore, the current study was conducted with the objectives to evaluate the pattern, frequency, management, and risk factors associated with AEs and as well as their impact on treatment outcomes among MDR-TB patients.…”

A Comprehensive Review on Long vs. Short Regimens in Multidrug-Resistant Tuberculosis (MDR-TB) Under Programmatic Management of Drug-Resistant Tuberculosis (PMDT)

“…PMDT involves the execution of treatment regimens, and recent studies have compared the effectiveness of individualized LTR and standardized STR. These investigations reveal that STR demonstrates superior antimicrobial activity against MDR-TB, leading to significantly earlier treatment completion when contrasted with LTR [ 33 ]. The comprehensive nature of PMDT addresses the challenges posed by MDR-TB and XDR-TB, with continuous updates to its guidelines and regimens reflecting the latest evidence and best practices.…”

“…These STRs, designed to last nine to 12 months, have demonstrated superior treatment success and reduced rates of loss to follow-up when compared to individualized LTR [ 8 ]. In a study comparing STR with LTR, the former exhibited heightened antimicrobial activity against MDR-TB, leading to significantly earlier treatment completion [ 33 ]. However, it is essential to acknowledge that STRs carry a higher risk of failure or relapse in the presence of resistance to component drugs [ 8 ].…”

“…The associated costs serve as a formidable barrier, hindering access to essential resources needed for effective treatment. Additionally, the incidence of adverse events during the course of treatment is a critical consideration that can significantly impact patient outcomes [ 33 ]. Strategizing effective management strategies for both cost and adverse events is essential for optimizing the overall treatment experience.…”