Relapse after treatment with standardized all-oral short regimens for rifampicin-resistant tuberculosis (RR-TB): A systematic review and meta-analysis

Background Treatment for rifampicin-resistant tuberculosis (RR-TB) has been shortened to 12 months or less, with duration depending on the regimen used and treatment response. Treatment shortening has the potential to increase the risk of relapse, with a new episode of RR-TB after cure or completion. The proportion of relapses after standardized all-oral short (12 months or less) RR-TB regimens has not yet been systematically reviewed, which is the main objective of this review. Methods This is a systematic review and meta-analysis. PubMed, Web of Science and Google scholar databases were systematically investigated to identify studies published between January 2018 and November 2023. Characteristics of studies, demographic data, baseline clinical condition, resistance profile, and definitions used for relapse, failure, and end-of-treatment outcomes are summarized in tables and graphs. Pooled proportions are estimated for relapse. Results A total of ten studies were included in this review and meta-analysis, representing 1792 participants. Seven studies were clinical trials and two were cohorts. Five studies investigated all-oral six-month regimens composed of bedaquiline, pretomanid, and linezolid (BPaL). The remaining studies assessed other standardized all-oral short regimens, with treatment duration between 6 and 12 months. Post-treatment follow-up (PTFU) duration ranged from 6 to 30 months. The pooled proportion estimate of relapse was 2·0% (95 % CI, 1·0-3·0%) for all and BPaL-based regimens. Treatment extension due to poor treatment response was poorly documented. Conclusion This review showed that the proportion of relapse in RR-TB patients treated with standardized short all-oral regimens was low. The low relapse proportion is similar to what was achieved for drug-susceptible Tuberculosis patients treated with first-line rifampicin-containing regimens. However, most data came from trial settings, and in some studies the post-treatment follow-up was short. Studies of large programmatic cohorts with longer post-treatment follow-up periods are needed to confirm the low relapse rate shown in the clinical trials.