With tuberculosis (TB) reemerging as the leading infectious disease killer in 2023, new research shows crucial insights and experimental new strategies for treating extensively- drug-resistant TB (XDR TB).
The findings of these research were presented at The Union World Conference on Lung Health in Bali, Indonesia. One of them is the end-TB Q trial evaluating the efficacy and safety of bedaquiline, delamanid, clofazimine, and linezolid (BDCL) compared to World Health Organization (WHO)-recommended longer regimens.
The results showed high rates of favourable outcomes overall in the shorter treatment strategy (using BDCL), although slightly lower to those in the control arm; with 87% of participants undergoing the shorter, experimental strategy, compared to 89% in the control.
BCDL started at six months – and extended to nine months in case of delayed treatment response – achieved excellent results in people with non-severe TB disease at the start of treatment (93% cure).
However, in people with severe TB disease, BCDL for nine months was not sufficient to prevent relapse compared to the long regimen.
Lorenzo Guglielmetti, MD, PhD, Médecins Sans Frontières Director for the endTB project and Co-Principal Investigator of the trial said: “Our trial innovated in several important ways. Since we know that treatment for TB is not ‘one size fits all’, we tested a strategy that tailored treatment duration to disease severity and treatment response based on simple criteria.
“Emerging evidence highlights that the BCDL regimen may be well suited for people with non-severe TB disease but riskier for those with severe disease.”
New data from a pivotal trial undertaken by the NIH-funded IMPAACT network including experts from Stellenbosch University on the pharmacokinetics and safety of the antibiotic bedaquiline in infants, children and adolescents with drug-resistant TB was also presented. The data indicated that the treatment is both safe and well-tolerated.
The investigators concluded that the findings, which informed WHO guidelines and access to bedaquiline, are crucial in further optimising drug-resistant TB in children– providing new, key data and access in children.
Researcher Prof Simon Schaaf said: “The P1108 trial has paved the way for access, finally, to effective, shorter and safer treatment for children with drug-resistant TB. For too long children with TB have been left behind.”
A TBNet-led study has attempted to describe treatments for people with XDR-TB under the WHO’s definition of the condition, updated in 2021, which considers XDR-TB to include resistance to any fluoroquinolone and at least one Group A drug (bedaquiline or linezolid).
Study participants were prescribed, on average, six anti-TB drugs. Results indicate that each additional effective drug significantly reduces the odds of unsuccessful outcomes.
The researchers behind the study explained that this highlights the need for optimised drug susceptibility testing methods and expanding access to new TB compounds for people with life-threatening TB.
Speaking from Bali, Dr. Cassandra Kelly-Cirino, Executive Director of The International Union Against Tuberculosis and Lung Disease (The Union) said: “Antimicrobial resistance is among the greatest global health threats we face today. For people at-risk of TB, this threat is multiplied”.
“The new research presented at the Union Conference this week represents an invaluable step in managing this challenge and in offering hope to patients of all ages living with extensively drug-resistant TB”.
