Effect of a modified regimen on drug-sensitive retreated pulmonary tuberculosis: A multicenter study in China

Abstract

Background and objective: Retreatment pulmonary tuberculosis (PTB) still accounts for a large proportion of tuberculosis, and the treatment outcome is unfavorable. The recurrence of retreatment PTB based on long-term follow-up has not been well demonstrated. This study aimed to evaluate effect of a modified regimen on drug-sensitive retreated pulmonary tuberculosis.

Methods: This multicenter cohort study was conducted in 29 hospitals from 23 regions of China from July 1, 2009, to December 31, 2020. Patients were divided into two treatment regimen groups including experimental group [modified regimen (4H-Rt2-E-Z-S(Lfx)/4H-Rt2-E)]and control group [standard regimen (2H-R-E-Z-S/6H-R-E or 3H-R-E-Z/6H-R-E)]. The patients enrolled were followed up of 56 months after successful treatment. We compared the treatment success rate, treatment failure rate, adverse reaction rate, and recurrence rate between two regimens. Multivariate Cox regression model was used to identify the potential risk factors for recurrence after successful treatment with proportional hazards assumptions tested for all variables.

Results: A total of 381 patients with retreatment PTB were enrolled, including 244 (64.0%) in the experimental group and 137 (36.0%) in the control group. Overall, the treatment success rate was significant higher in the experimental group than control group (84.0 vs. 74.5%, P = 0.024); no difference was observed in adverse reactions between the two groups (25.8 vs. 21.2%, P > 0.05). A total of 307 patients completed the 56 months of follow-up, including 205 with the modified regimen and 102 with the standard regimen. Among these, 10 cases (3.3%) relapsed, including 3 in the experimental group and 7 in the control group (1.5% vs 6.9%, P = 0.035). Reduced risks of recurrence were observed in patients treated with the modified regimen compared with the standard regimen, and the adjusted hazard ratio was 0.19 (0.04-0.77).

Conclusion: The modified retreatment regimen had more favorable treatment effects, including higher treatment success rate and lower recurrence rate in patients with retreated drug-sensitive PTB.

Keywords: follow-up; modified regimen; pulmonary tuberculosis; recurrence; retreatment.

Figure 1

Study design and drug regimens. Patients with drug-sensitive tuberculosis receive modified regimen (4H-L₂₋E-Z-S(F)/4H-L₂-E) or standard regimen 2H-R-E-Z-S/6H-R-E. H, isoniazid (INH); R, rifampicin (RIF); L, rifapentine (Rft); E, ethambutol (EMB); Z, pyrazinamide (PZA); S, streptomycin (Sm); F, levofloxacin (Lfx).

Figure 2

Flow chart of TB subjects enrolled in the study.

Figure 3

Study outcomes after 8 months according to the protocol-defined analysis and analysis based on the WHO definition. The figure shows study outcomes in the modified intention-to-treat population based on the WHO definitions with respect to study data after 8 months. Patients in the modified regimen group had a higher rate of successful treatment (cure plus no conversion) compared with those in the standard regimen group (χ² = 5.128, P = 0.024). ^*The value of P < 0.05 indicate statistical significance.

Figure 4

The recurrence probability in the control group (red) and the experimental group (green) during the follow-up period of 56 months. The recurrence of tuberculosis is defined as either a positive M. tb culture or a positive sputum smear fluorescence microscopy during the follow-up.