TB preventive therapy: What factors influence treatment discontinuation?

Time to discontinuation of tuberculosis (TB) preventive therapy does not significantly differ between patients with latent TB infection on 3-month regimens of isoniazid plus rifapentine vs 4-month regimens of rifampin. However, patients on isoniazid plus rifapentine often discontinue therapy due to treatment-related adverse events (AEs) or a joint patient-provider decision to stop, whereas those on rifampin often discontinue therapy due to social and congregate risk factors. These study results were published in Open Forum Infectious Diseases.

Researchers conducted a subanalysis of an observational cohort study that was performed between January 2016 and October 2017 to explore the timing and factors associated with the discontinuation of TB preventive therapy. Patients included in the analysis had latent TB infection and were on 3-month courses of isoniazid plus rifapentine or 4-month courses of rifampin. Data were obtained from clinical records of patients who visited 1 of 15 participating public health TB clinics and had at least 1 documented follow-up visit during a 6-month period. The primary outcomes included completion vs incompletion of TB preventive therapy and medical, social, and occupational risk factors for discontinuation. Mixed-effect Cox regression models were used to assess risk factors.

A total of 993 patients (aged 25-44 years, 48.0%; men, 51%; non-Hispanic Black, 31%) were included in the analysis, of whom 791 (80%) were assigned a 4-month course of rifampin and 202 (20%) were assigned a 3-month course of isoniazid plus rifapentine.

The choice of treatment did not differ by sex, birth origin, primary reason for evaluation, or patient medical and congregate risks for TB; however, the choice of treatment did vary by race/ethnicity, age at diagnosis, and social- and occupational-related risk factors.

The overall risk for treatment discontinuation was 27%, with a higher risk observed among patients on isoniazid plus rifapentine vs rifampin (31% vs 14%; P <.0001). There was no significant between-group difference in the mean time to treatment interruption (t, 0.12 weeks; 95% CI, -2.00 to 2.30), with a mean time of 4 weeks observed between treatment initiation and discontinuation.

Key risk factors for the discontinuation of isoniazid plus rifapentine included Hispanic race/ethnicity (hazard ratio [HR], 1.80; 95% CI, 1.20-2.90) and having experienced an AE over the course of therapy (HR, 4.30; 95% CI, 2.60-7.30). Patients born outside of the United States were less likely to discontinue treatment (HR, 0.59; 95% CI, 0.36-0.98).

Key risk factors for the discontinuation of rifampin included White race/ethnicity (HR, 5.00; 95% CI, 1.10-22.00), a history of substance misuse (HR, 12.00; 95% CI, 2.20, 69.00), and congregate living (HR, 21.00; 95% CI, 1.20-360.00). Compared with patients aged 0 to 24 years, discontinuations of rifampin were less likely among those aged 25 to 44 years (HR, 0.26; 95% CI, 0.09-0.75) and 45 to 64 years (HR, 0.11; 95% CI, 0.02-0.65).

In a multivariate analysis adjusted for TB disease risk, the researchers observed no other significant factors associated with the discontinuation of TB preventive therapy.

Study limitations include missing data, unmeasured confounders, the small sample size, potential selection bias, and the lack of detailed information on some factors that may have influenced treatment adherence and completion.

According to the researchers, “These findings underscore the importance of considering the multifaceted demographic and social risk factors influencing TPT [tuberculosis preventive therapy] non-adherence and discontinuation in clinical practice.”

References:

Baah M, Salmon-Trejo LAT, et al. Factors associated with the discontinuation of two short-course tuberculosis preventive therapy in programmatic settings in the United States. Open Forum Infect Dis. Published online June 6, 2024. doi:10.1093/ofid/ofae313

Source: Infectious Disease Advisor