At Long Last: Short, All-Oral Regimens for Multidrug-Resistant Tuberculosis in the United States

Abstract

Multidrug resistant tuberculosis (MDR-TB) has historically required longer treatment regimens that were associated with higher unfavorable outcomes and side effects rates compared to drug susceptible tuberculosis (DS-TB). During the last decade, several studies conducted mostly in high incidence settings, have shown that MDR-TB can be successfully treated using all-oral shorter regimens of 6-9 months duration. In this paper, we review the evolution of MDR-TB treatment from the early long regimens with injectables agents (IA), followed by the shorter regimens with IA to the groundbreaking all-oral 6-9 months regimens. Finally, we propose a framework for implementation of the shorter all-oral regimens in the United States.

Updates in pulmonary drug‐resistant tuberculosis pharmacotherapy: A focus on BPaL and BPaLM

“…34,35 Historically, clinicians were forced to utilize long durations of regimens consisting of multiple anti-TB medications with relatively low potency and less sterilizing activity. 7,36 Given sub-optimal therapeutics, there was a decades long quest to identify medications that have sufficient activity and sterilizing activity to reliably cure drug-resistant TB in the absence of a rifamycin. 7 Isoniazid is another important first-line anti-TB medication because of its potency and early bactericidal activity (EBA).…”

“…7,36 Given sub-optimal therapeutics, there was a decades long quest to identify medications that have sufficient activity and sterilizing activity to reliably cure drug-resistant TB in the absence of a rifamycin. 7 Isoniazid is another important first-line anti-TB medication because of its potency and early bactericidal activity (EBA). [37][38][39] Despite the potency of INH against M. tuberculosis, INH resistance in the presence of RIF susceptibility is common worldwide, with a global average of 7.1% in new TB cases and even higher in cases that were previously treated.…”

“…As mentioned previously, adverse events and poor outcomes are more common in the treatment of MDR-TB compared to drugsusceptible TB due to longer drug exposures and the use of less potent or inactive drugs, respectively. [4][5][6][7][8][9][10]49 Serious adverse events, such as hearing loss, vestibular disorders, and visual impairment, often lead to regimen discontinuation and medications adherence issues in patients with drug-resistant TB. 49 One strategy to achieving safe and effective treatment is to shorten the duration of therapy while utilizing novel agents that maintain sterilizing ability.…”

“…However, when susceptibility is demonstrated to all agents in the regimen, either the BPaL or BPaLM regimen would be preferred compared to a longer duration regimen with injectable agents, to optimize treatment outcomes and reduce side effects. 7 In cases where the shorter, all oral regimens cannot be employed, longer duration individualized regimens should be utilized. 2,29 Due to limited evidence, the optimal duration for longer, individualized therapy remains unclear for patients with drug-resistant TB.…”

“…4,5 Unfortunately, longer regimens with injectable formulations have translated to an increase in toxicities, treatment failures, deaths, and health care and societal costs compared to shorter regimens. [4][5][6][7][8][9][10] Despite decades of suboptimal outcomes with traditional therapeutics for drugresistant TB, potent, all-oral regimens with shorter durations have begun to arise due to the availability of repurposed or new anti-TB medications and their demonstrated efficacy in clinical trials. [11][12][13][14]…”