The need to accelerate access to new drugs for multidrug-resistant tuberculosis

Abstract

Approximately half a million people are thought to develop multidrug-resistant tuberculosis annually. Barely 20% of these people currently receive recommended treatment and only about 10% are successfully treated. Poor access to treatment is probably driving the current epidemic, via ongoing transmission. Treatment scale-up is hampered by current treatment regimens, which are lengthy, expensive, poorly tolerated and difficult to administer in the settings where most patients reside. Although new drugs provide an opportunity to improve treatment regimens, current and planned clinical trials hold little promise for developing regimens that will facilitate prompt treatment scale-up. In this article we argue that clinical trials, while necessary, should be complemented by timely, large-scale, operational research that will provide programmatic data on the use of new drugs and regimens while simultaneously improving access to life-saving treatment. Perceived risks – such as the rapid development of resistance to new drugs – need to be balanced against the high levels of mortality and transmission that will otherwise persist. Doubling access to treatment and increasing treatment success could save approximately a million lives over the next decade.

Recent controversies about MDR and XDR‐TB: Global implementation of the WHO shorter MDR‐TB regimen and bedaquiline for all with MDR‐TB?

“…There are clearly some settings where RR/MDR‐TB is strongly associated with second‐line drug resistance, and therefore with low proportions of patients who would benefit from the shorter regimen . In these settings, expanded access to the new TB drugs, following WHO guidance, is urgently needed . However, globally, close to a half of all MDR‐TB patients do not have resistance to fluoroquinolones, SLID or both, and in some high burden countries such as South Africa, close to 80% of MDR‐TB patients would likely be eligible for the shorter regimen…”

“…Unfortunately, patient support has not been prioritized across many high burden settings, particularly as the number of patients receiving treatment increases . While the new, all‐oral regimens currently being tested in clinical trials are likely to be considerably more tolerable for patients, RCTs in TB treatment are notoriously slow, and results will not be available for several years . In the meantime, the shorter regimen, although not ideal, is beneficial for patients in terms of duration and health systems in terms of capacity and cost.…”

Infection Control for Drug-Resistant Tuberculosis: Early Diagnosis and Treatment Is the Key: Table 1.

“…In addition, a smaller burden of patients requiring hospitalization allows more effective use of hospital beds, potentially allowing for smaller wards or single-bed rooms, and prioritization of clinician time for patients who need it most. The provision of more effective treatment regimens, utilizing new and repurposed drugs, from the outset should also reduce the proportion of patients for whom treatment fails and the consequent transmission risk associated with these individuals [40].…”

Linezolid in drug-resistant tuberculosis: haste makes waste

“…While we agree with Bhuniya and colleagues that it is important to preserve the efficacy of newer and repurposed antituberculosis drugs such as linezolid (LZD), we also advocate greater access to these drugs in regimens containing at least two other likely effective drugs, within optimally administered treatment programmes with sufficient monitoring and adherence support [2]. Treatment outcomes are poor for MDR-TB, with <50% treatment success globally and in both settings included in our study [3,4]; outcomes are even worse for patients infected with strains with additional second-line resistance [5].…”