Standardised shorter regimens versus individualised longer regimens for multidrug-resistant TB

We sought to compare the effectiveness of two WHO-recommended regimens for the treatment of rifampin- or multidrug-resistant (RR/MDR) tuberculosis: a standardised regimen of 9–12 months (the “shorter regimen”), and individualised regimens of ≥20 months (“longer regimens”). We collected individual patient data from observational studies identified through systematic reviews and a public call for data. We included patients meeting WHO eligibility criteria for the shorter regimen: not previously treated with second-line drugs, and with fluoroquinolone- and second-line injectable agent-susceptible RR/MDR tuberculosis. We used propensity score matched, mixed-effects meta-regression to calculate adjusted odds ratios and adjusted risk differences (aRD) for failure or relapse, death within 12 months of treatment initiation, and loss to follow-up. We included 2625/3378 (77.7%) individuals from 9 studies of shorter regimens, and 2717/13104 (20.7%) from 53 studies of longer regimens. Treatment success was higher with the shorter regimen than with longer regimens (pooled proportions: 80.0% versus 75.3%), due to less loss to follow-up with the former (aRD, −0.15 95%CI: −0.17 to −0.12). The risk difference for failure or relapse was slightly higher with the shorter regimen overall (0.02, 95%CI: 0 to 0.05), and greater in magnitude with baseline resistance to pyrazinamide (0.12, 95%CI: 0.07 to 0.16), prothionamide/ethionamide (0.07, 95%CI: −0.01 to 0.16), or ethambutol (0.09, 95%CI: 0.04 to 0.13). In patients meeting WHO criteria for its use, the standardised shorter regimen was associated with substantially less loss to follow-up during treatment as compared to individualised longer regimens, and with more failure/relapse in the presence of resistance to component medications. Our findings support the need to improve access to reliable drug susceptibility testing.