BPаL: the first program results of operational study within the framework of the project ICF «Оrganization for Appropriate Technology in Health» and facilitating the expansion this regimen in Ukraine

Abstract

Objective — to study the programmatic results of the efficacy and tolerability of the standard combina­tion BPaL regimen for patients with multidrug-resistant tuberculosis failures and pre-XDR-TB. Materials and methods. Treatment of patients with BPaL regimen took place within the framework of the Project of the ICF «Organization for Appropriate Technology in Health» on the basis of the National Institute of Phthisiology and Pulmonology named after F.G. Yanovsky NAMS of Ukraine (NIFP NAMS) of Ukraine as the operational study «Pilot study to assess the effectiveness and safety of antimycobacte­rial therapy with BPaL regimen in Ukraine». Recruitment lasted from November 2020 to March 2022. The composition of the BPaL regimen, which was prescribed in the operational study: bedaquiline — 400 mg daily for the first 2 weeks, with a subsequent transition to 200 mg every other day, linezolid 1200 mg daily (with the possibility of changing the dose or canceling it after at least 4 consecutive weeks of its use), pretomanid 200 mg daily. The standard duration of treatment is 6 months (26 weeks or 182 doses). Extended duration up to 9 months — if a positive culture result (or reversion) is registered after 4 months of treatment and insufficient dynamics after 6 months of treatment. The implementation plan was 135 patients with pre-XDR-TB or failure of previous courses without exclusion criteria. Results and discussion. Despite the significant challenges/barriers that have arisen on the way to the implementation of OS, the effectiveness of the BPaL regimen, obtained within the framework of the Project and implemented on the basis of the NIFP of NAMS of Ukraine, fully corresponds to the results of clinical trials of various variants of the BPaL regimen: successful treatment was obtained in 91.5 % patients. The regimen turned out to be quite safe: complete cancellation of BPaL due to SAEs was carried out only in 4 patients, all others, despite the occurrence of AEs of various degrees of severity in 81.4 % of patients, managed to maintain treatment and successfully complete BPaL. Moreover, complete removal of linezolid from the composition of BPaL was carried out only in 8.2 % of patients. The main AEs were expected to be myelosuppression and peripheral neuropathy (the main AEs of linezolid at a high dose of 1200 mg per day). But in addition to these adverse events, hepatotoxicity was recorded in almost every 4th patient. It should be noted that these data completely match with the results of clinical trials. Such high results were achieved thanks to the close cooperation of partners, training and education of specialists of NIFP NAMS of Ukraine, and as a result — careful treatment of each patient, close monitoring of the condition of each of them, and a people-oriented approach. Conclusions. Ukraine is the first country in the world where the treatment of TB patients with the BPaL regimen as part of operational studies with excellent results was performed, which also paved the way for the current expansion of BPaL treatment in Ukraine even during the war.