Steroids Added to TB Treatment May Reduce Mortality

Diedtra Henderson

March 14, 2013

Adjunctive corticosteroids may reduce mortality from all forms of tuberculosis by 17%, no matter which organ group was affected, according to a meta-analysis.

Julia A. Critchley, DPhil, from the Division of Population Health Sciences and Education, St. George's, University of London, United Kingdom, and colleagues report their findings in the March issue of the Lancet Infectious Diseases.

According to Dr. Critchley and colleagues, 8.7 million cases of tuberculosis are diagnosed each year, with nearly 1.4 million deaths. The condition is particularly lethal in some regions where health systems are fragile and high numbers of patients also have been diagnosed with HIV or are poor or elderly.

Although steroids have systemic effects, their benefits in blunting the damaging effect of the body's inflammatory response to infection are thought to be organ-specific for patients with tuberculosis. To put that theory to the test, the research team searched for studies with patients diagnosed with any form of tuberculosis published from 1955 to 2012. They included 41 trials involving 3560 treated patients and 2982 control patients in their meta-analysis. The types of steroids prescribed varied, as did dose and duration.

"Mortality was lower in patients who were given steroids for every included tuberculosis organ system; the overall reduction in mortality with steroids was 17% (risk ratio [RR] 0.83, 95% [confidence interval] CI 0.74–0.92)," the authors write. "We noted no significant heterogeneity between trials within or between organ systems (I ² within organ systems: pulmonary 14%, meningitis 12%, pericarditis 0% [I ² could not be calculated for pleurisy]; between organ systems 0%)."

In an accompanying comment, Guy E. Thwaites, PhD, from the Centre for Clinical Infection and Diagnostics Research, Guy's and St. Thomas' Hospitals National Health Service Foundation Trust, London, writes that the results "must be interpreted cautiously" because of weaknesses in the underlying trials. Moreover, a recently identified polymorphism in the gene that encodes leukotriene A4 hydrolase could clarify which patients are more susceptible to tuberculous meningitis. Corticosteroids reduced mortality in patients with the hyperinflammatory phenotype but were detrimental to patients with the hypoinflammatory phenotype.

These preliminary findings and the meta-analysis "should stimulate the reappraisal of adjunctive corticosteroids for pulmonary tuberculosis by new randomised controlled trials," Dr. Thwaites writes.

Limitations include the small size of the studies, which left most underpowered, and the less stringent reporting methods at the time the trials were conducted, which in many cases predated the use of modern combination therapies. In addition, many trials occurred before the advent of HIV and the rise of drug-resistant tuberculosis. Because adverse events are poorly reported in older studies, the authors advocate for new trials that can more accurately assess the benefits and risks of adjunctive corticosteroid use.

"Our analysis suggests a benefit from steroids that seems to be consistent across organ systems," the authors conclude. "Even in the absence of contemporary data for rifampicin-based regimens for treatment of pulmonary tuberculosis, if this result shows a true systemic effect across organ systems, it provides indirect evidence to suggest that steroids could be of benefit in pulmonary tuberculosis."

Support for this study was provided by the UK Department for International Development. The authors and commentator have disclosed no relevant financial relationships.

Lancet Infect Dis. 2013;13:186-188, 223-237. Article abstract, Comment extract