Post-treatment recurrence risk low for multidrug-resistant TB

The risk for multidrug (MDR)- and rifampicin-resistant tuberculosis (TB) recurrence is low following long-term treatment with bedaquiline or delamanid, according to results of a study published in Clinical Infectious Diseases.

Investigators at Harvard Medical School in Massachusetts sourced data from the endTB Observational Study, a prospective cohort study conducted between 2015 and 2018 in 17 countries. Patients (N=1991) included in the analysis were those with MDR or rifampicin-resistant TB infection who received initial treatment with either bedaquiline or delamanid. The researchers estimated the risk for TB recurrence at 6 months following treatment completion, both overall and by HIV status. Inverse probability weighting was used to account for patients with missing follow-up data.

Five strategies were developed to assess mortality outcomes in relation to TB recurrence. In the “observed recurrence” scenario, mortality outcomes were included in the analysis but were not considered recurrences. In the “hypothetical recurrence” scenario, all mortality outcomes were excluded. In the “composite/any” scenario, recurrent TB and all-cause mortality outcomes were included. In the “composite/probable” scenario, recurrent TB and mortality due to TB or an unknown cause were included. In the “composite/explicit” scenario, recurrent TB and only TB-associated mortality were included.

The study population primarily comprised individuals aged 20 to 44 years (64.9%). Overall, 36.3% of patients had cavitary disease, 14.8% had diabetes, 11.9% had HIV infection, and 9.3% had hepatitis C virus infection.

Within 6 months of treatment completion, mortality occurred in 17 (0.9%) patients. Of the mortality events, 11 were due to causes other than TB infection, 4 were of unknown causes, and 2 were attributed to TB infection. The researchers noted that mortality outcomes were more likely among patients aged 60 years and older.

A total of 10 (0.5%) patients experienced TB recurrence within 6 months of treatment completion.

After adjustment for missing follow-up data, the overall risk for recurrent TB infection per 1000 patients across the 5 recurrence scenarios was as follows:

• Observed recurrence (7.4; 95% CI, 3.5-12.90);
• Hypothetical recurrence (7.6; 95% CI, 3.6-13.1);
• Composite/any recurrence (25.5; 95% CI, 15.4-38.1);
• Composite/probable recurrence (11.7; 95% CI, 6.5-18.3); and
• Composite/explicit recurrence (8.6; 95% CI, 4.2-14.6).

For patients with vs without HIV infection, the relative risk (RR) for TB recurrence across the 5 recurrence scenarios was as follows:

• Observed recurrence (RR, 1.2; 95% CI, 0.1-5.7);
• Hypothetical recurrence (RR, 1.2; 95% CI, 0.2-4.9);
• Composite/any recurrence (RR, 0.6; 95% CI, 0.1-1.7);
• Composite/probable recurrence (RR, 0.7; 95% CI, 0.1-2.8); and
• Composite/explicit recurrence (RR, 1.0; 95% CI, 0.1-4.0).

Owing to the small number of recurrences and mortality events, the association between HIV status and the risk for recurrent TB infection was inconclusive.

In sensitivity analyses in which patients with missing follow-up data were excluded, the risk for recurrent TB infection was 8.0 and 8.1 per 1000 patients in the observed recurrence and hypothetical recurrence scenarios, respectively.

This study is limited by the relatively short follow-up period, as evidence suggests most recurrent TB infections occur within 12 months of treatment completion. In addition, the researchers did not distinguish between relapse and reinfection, and collider bias may have affected estimates of recurrence in patients with HIV infection.

According to the researchers, “Rigorous analyses of post-TB treatment recurrence are needed to accurately understand whether certain groups require closer monitoring…”

Disclosures: Multiple study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

By Jessica Nye

References:

Sauer SM, Mitnick CD, Khan U, et al. Estimating post-treatment recurrence after multidrug-resistant tuberculosis treatment among patients with and without HIV: the impact of assumptions about death and missing follow-up. Clin Infect Dis. Published online September 29, 2023. doi:10.1093/cid/ciad589

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