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

Objective: To compare the effectiveness of second line injectables containing shorter (duration 9-12 months) and longer treatment regimens (LTR, duration & GE; 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 & GE; 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 & GE; 1 month.