Steroids reduce mortality risk for people taking TB treatment

Corticosteroid treatment is associated with a reduced risk of mortality for people taking tuberculosis (TB) therapy, results of a meta-analysis published in The Lancet Infectious Diseases show. Treatment with steroids was associated with a significant 17% reduction in mortality risk, and the benefits were apparent across all TB types.  

In an editorial accompanying the study, Dr Guy Thwaites of St Thomas’ Hospital, London, said that the results of the analysis were not sufficient to change current prescribing practices in cases of pulmonary TB. However, he believed, “they should stimulate the reappraisal of adjunctive corticosteroids…by new randomised controlled trials.”

Each year, there are approximately 8.7 million new cases of TB and 1.4 million deaths caused by the infection.

There is currently controversy about the use of corticosteroids as an adjunct to TB treatment. Previous systematic reviews have shown that this the use of steroids leads to significant reductions in mortality for people with TB meningitis. The benefits of corticosteroid therapy for other types of TB are less certain. Moreover, there are concerns that their use could worsen TB disease or that there would be a significant risk of drug interactions.

Nevertheless, as steroids have an anti-inflammatory effect there are grounds for believing their benefits are not limited to a specific organ.

A team of investigators from the United Kingdom therefore performed a systematic review and meta-analysis of studies examining the impact of adjunctive corticosteroid therapy on mortality risk for people taking TB treatment.

There were no restrictions on studies with respect to age group, setting, disease type or co-infection with HIV or any other disease. Randomised and non-randomised studies were included in the analysis.

A total of 41 studies conducted between 1955 and 2011 were identified. They included 3560 participants who received steroids and 2982 participants in control groups. A total of 18 studies involved people with pulmonary TB, nine were in people with TB meningitis, seven involved people with TB pleurisy, six recruited people with TB pericarditis and one was in people with TB peritonitis.

In all, 23 studies were conducted before 1990 and therefore the introduction of modern rifampicin-based TB therapy.

The types of steroids used, their doses and the duration of therapy varied widely.

Overall, use of corticosteroids was associated with a 17% reduction in mortality risk (RR = 0.83; 95% CI, 0.74-0.92). This reduction in risk was consistent across all groups, whichever organ was affected.

Exclusion of non-randomised studies yielded almost identical results.

Reporting of side-effects was poor, but incidence of serious adverse events did not differ between the steroid and control groups.

Studies conducted before the introduction of rifampicin-containing regimens showed that steroids significantly reduced the mortality risk of patients with pulmonary TB (RR = 0.72; 95% CI, 0.40-1.29). Only one study reported on mortality in patients with pulmonary TB in the rifampicin era, and this showed that steroids had no benefit.

For TB meningitis and pericarditis there was no difference when results were stratified according to the use of rifampicin regimens. There were no rifampicin studies for TB peritonitits and only one for TB pleurisy.

Pooling the results of all rifampicin-era studies showed that steroids reduced mortality risk by 15% (RR = 0.85; 95% CI, 0.74-0.98).

Three small studies involved people with HIV. There was little evidence that adjunctive therapy with steroids had any benefit, but the investigators emphasise that these studies were statistically underpowered.

“Overall, corticosteroids resulted in a significant and clinically important reduction in mortality, whatever the organ group affected,” comment the authors. “The exact mechanisms of the benefit are not clear, but are related to the host response to the tuberculosis pathogen (including inflammation), and so effects in one organ system might well be relevant to others with respect to mortality outcomes.”

However, neither the investigators not the author of the editorial regard the results of the meta-analysis as definitive. In particular, they highlight the lack of data concerning the benefits of steroids for patients with pulmonary TB treated with rifampicin-based regimens.

“New clinical trials of corticosteroids in patients with pulmonary tuberculosis (both infected and uninfected with HIV) are needed to assess whether…clinical benefits remain in the era of modern anti-tuberculosis chemotherapy,” write the investigators. “At least 10 000 patients would be needed for a new trial to be adequately powered for mortality.”