Toward Earlier Inclusion of Pregnant and Postpartum Women in Tuberculosis Drug Trials: Consensus Statements From an International Expert Panel

Abstract

Tuberculosis is a major cause of morbidity and mortality in women of childbearing age (15-44 years). Despite increased tuberculosis risk during pregnancy, optimal clinical treatment remains unclear: safety, tolerability, and pharmacokinetic data for many tuberculosis drugs are lacking, and trials of promising new tuberculosis drugs exclude pregnant women. To advance inclusion of pregnant and postpartum women in tuberculosis drug trials, the US National Institutes of Health convened an international expert panel. Discussions generated consensus statements (>75% agreement among panelists) identifying high-priority research areas during pregnancy, including: (1) preventing progression of latent tuberculosis infection, especially in women coinfected with human immunodeficiency virus; (2) evaluating new agents/regimens for treatment of multidrug-resistant tuberculosis; and (3) evaluating safety, tolerability and pharmacokinetics of tuberculosis drugs already in use during pregnancy and postpartum. Incorporating pregnant women into clinical trials would extend evidence-based tuberculosis prevention and treatment standards to this special population.

Tuberculosis clinical presentation and treatment outcomes in pregnancy: a prospective cohort study

“…Although evidence is limited, there is growing observational evidence that some DR-TB medications are safe during pregnancy [19,20,28]. Pregnant women should have prompt access to advances in TB treatment; however, due to the frequent exclusion of pregnant women from TB research studies, they are often a neglected population [24]. Notably, there is a dual benefit to treating a pregnant woman sick with TB: both to cure her and to eliminate the risk of her infecting her infant.…”

Advances in clinical trial design: Weaving tomorrow’s TB treatments

“…As a result, evidence for TB treatment during pregnancy or breastfeeding has come mainly from case reports and small series [54]. Including pregnant women in TB trials would provide more rigorous evidence of safety and activity than post-marketing surveillance [55]. TB trials should include experts in maternal-fetal medicine and the care of pregnant women who can determine reasonable approaches for risk/benefit assessment in this population.…”

Pulmonary Infections in Pregnancy

“…27 There is a consensus that pregnant women with active TB should receive treatment. 47 However, the regimen varies depending on HIV status and which guidelines are followed. The WHO recommends the standard adult doses of isoniazid (INH), rifampin, ethambutol, and pyrazinamide (PZA) for HIV-infected or HIV-uninfected pregnant women with TB.…”