Operational Study of Efficacy and Safety of 9-Month Multi- and Pre-Extesively Drug Resistant Tuberculosis Therapy in the Russian Federation

Background. The World Health Organization (WHO) recommends conducting regional operational studies of fully oral modified shorter treatment regimens for multidrug/rifampicin-resistant tuberculosis in different countries to achieve an indicator of tuberculosis treatment effectiveness. Aims — to evaluate the efficacy and safety of 9-month, fully oral four-component treatment regimen for patients with MDR and pre-XDR-TB in two administrative regions of the Russian Federation. Methods. In frame of operational research conducted in the Arkhangelsk and Vladimir regions, 167 MDR-TB patients started 9-month treatment. Based on results of drug susceptibility testing of mycobacteria to fluoroquinolones, 134 participans received therapy with combination of levofloxacin (Lfx), bedaquiline (Bdq), linezolid (Lzd), clofazimine (Cfz), one patient — with levofloxacin (Lfx), bedaquiline (Bdq), delamanid (Dlm), clofazimine (Cfz), and 32 patients with — bedaquiline (Bdq), linezolid (Lzd), delamanid (Dlm) and clofazimine (Cfz). The molecular genetic verification of MDR-TB was 98.2%. HIV and hepatitis C co-infection was confirmed for 13.2% and 16.8% of participants, respectively. Adults, two teenagers and a pregnant woman participated in the study. Results. Favorable treatment outcomes were registered for 137 (82%) patients. Two of them had recurrence of the active TB disease. 15 (9%) patients were lost-to-follow-up, 7 (4.2%) patients had failure outcomes, and 8 (4.8%) patients died during treatment. On average, the culture conversion occurred after the first month of treatment. Active safety monitoring revealed 483 adverse events in 167 patients, the most frequent were: hepatotoxic reaction (in 89 patients, 53.3%), anemia (in 62 patients, 37.1%), QT prolongation (in 41 patients, 24.6%), polyneuropathy (in 45 patients, 26.9%). The frequency of serious adverse events was 9.5% of total number of adverse events. Conclusions. The results of an operational study of fully oral 9-month four-component treatment regimens demonstrate the achievement of WHO tuberculosis treatment effectiveness indicators (more than 80%), and low level of serious adverse events. They can be recommended for the national clinical guidelines.