Title: Corticosteroids for prevention of tuberculosis mortality
Abstract: We read with keen interest the meta-analysis by Julia Critchley and colleagues,1Critchley JA Young F Orton L Garner P Corticosteroids for prevention of mortality in people with tuberculosis: a systematic review and meta-analysis.Lancet Infect Dis. 2013; 13: 223-237Summary Full Text Full Text PDF PubMed Scopus (140) Google Scholar and we would like to emphasise some important issues. The only populations in which clinical trials of corticosteroids have shown improved outcomes in tuberculosis are HIV-seronegative patients with tuberculous meningitis and tuberculous pericarditis.1Critchley JA Young F Orton L Garner P Corticosteroids for prevention of mortality in people with tuberculosis: a systematic review and meta-analysis.Lancet Infect Dis. 2013; 13: 223-237Summary Full Text Full Text PDF PubMed Scopus (140) Google Scholar Evidence supporting use of corticosteroids in other clinical situations is poor. However, Critchley and colleagues1Critchley JA Young F Orton L Garner P Corticosteroids for prevention of mortality in people with tuberculosis: a systematic review and meta-analysis.Lancet Infect Dis. 2013; 13: 223-237Summary Full Text Full Text PDF PubMed Scopus (140) Google Scholar conclude that corticosteroids could be effective in reducing mortality in all forms of tuberculosis, including pulmonary tuberculosis. The overall results in this meta-analysis are weighted in favour of glucocorticoids because of the primary benefit noted with tuberculous meningitis, and not with pulmonary tuberculosis. To consider the results of all these forms of tuberculosis together and to conclude that the effect on mortality might be consistent across the range of the disease is inappropriate, especially in the context of the developing nations, which account for most global tuberculosis burden. In these countries, the results of the meta-analysis could be misinterpreted by physicians managing patients with tuberculosis. The results also have global implications in view of WHO tuberculosis strategy, which does not recommend steroids for pulmonary and pleural tuberculosis. Complications in tuberculous meningitis occur predominantly as a result of the inflammatory response, which can be associated with long-term neurological sequelae due to hydrocephalus, arachnoiditis, and vasculitic infarcts. Also, a high risk of death and disability exists in tubeculous meningitis despite combination chemotherapy regimens.2Kadhiravan T Deepanjali S Role of corticosteroids in the treatment of tuberculosis: An evidence-based update.Indian J Chest Dis Allied Sci. 2010; 52: 153-158PubMed Google Scholar Therefore, use of anti-inflammatory drugs such as corticosteroids seems logical. By contrast, more than 95% of patients with pulmonary tuberculosis recover uneventfully without major complications with multidrug treatment. The most important finding is that not one patient died in four of the five trials that assessed the effects of steroids in pulmonary tuberculosis in the era of multidrug treatment.1Critchley JA Young F Orton L Garner P Corticosteroids for prevention of mortality in people with tuberculosis: a systematic review and meta-analysis.Lancet Infect Dis. 2013; 13: 223-237Summary Full Text Full Text PDF PubMed Scopus (140) Google Scholar The only trial that did report deaths included only patients with HIV who received high doses of glucocorticoids.3Mayanja-Kizza H Jones-Lopez E Okwear A et al.Immunoadjuvant prednisolone therapy for HIV-associated tuberculosis: a phase 2 clinical trial in Uganda.J Infect Dis. 2005; 191: 856-865Crossref PubMed Scopus (110) Google Scholar Predictors of mortality in patients with HIV and tuberculosis differ from those in patients with tuberculosis without HIV. Moreover, the biological mechanisms of beneficial effect of corticosteroids in tuberculous meningitis and pericarditis are poorly understood. The possibility of increased risks of emergence of drug resistance in the era of multidrug-resistant tuberculosis, coexistent HIV infection, and immunosuppression leading to disease progression with co-administration of steroids to patients with pulmonary tuberculosis need to be carefully considered before doing further research. We declare that we have no conflicts of interest. Corticosteroids for prevention of mortality in people with tuberculosis: a systematic review and meta-analysisSteroids could be effective in reducing mortality for all forms of tuberculosis, including pulmonary tuberculosis. However, further evidence is needed since few recent trials have assessed the effectiveness of corticosteroids in patients with pulmonary tuberculosis. Full-Text PDF Corticosteroids for prevention of tuberculosis mortality – Authors' replyWe thank Karan Madan and colleagues for their comments. Our aim was to summarise the trial evidence for adjunctive steroid therapy in tuberculosis across all organ systems to look for evidence of consistent effects, and open a debate as to whether there is a “class effect”. Their letter is part of this debate. Full-Text PDF