Corticosteroid effects on sputum culture in pulmonary tuberculosis: a meta-regression analysis

There is increasing interest in the potential role of adjunctive anti-inflammatory therapy to accelerate tuberculosis (TB) treatment. Sputum culture conversion is an important biomarker predictor of durable TB cure.

This study used meta-regression analysis to examine the relationship between corticosteroid dose and sputum culture conversion, using published data from controlled clinical trials including 1806 corticosteroid-treated TB patients.

Linear models with 2 or 3 variables, including corticosteroid dose and the proportion of culture positive control subjects, predicted therapeutic benefit of corticosteroids at 1 and 2 months. The 3-variable model predicted that 134 mg of prednisolone per day, given together with standard 4-drug TB chemotherapy, would reduce the proportion of positive culture at 2 months from 15% to 2%. The estimate accounts for a 50% reduction in steroid exposure due to rifampin. A proportion of 2% of subjects with positive cultures at 2 months has been proposed as a target for new 4-month TB regimens.

These positive findings must be tempered by recognition that the metabolic and cardiovascular risks of corticosteroids administered at this dose for this duration are unlikely to be acceptable when examined from a patient-level benefit-risk perspective. In future research studies to shorten TB treatment, biologic anti-inflammatory therapies with similar therapeutic effects but superior safety profiles should be considered.