Adjunctive steroid therapy for managing pulmonary tuberculosis.
BACKGROUND
Tuberculosis causes approximately 8.6 million disease episodes and 1.3 million deaths worldwide per year. Although curable with standardized treatment, outcomes for some forms of tuberculosis are improved with adjunctive corticosteroid therapy. Whether corticosteroid therapy would be beneficial in treating people with pulmonary tuberculosis is unclear.


OBJECTIVE
To evaluate whether adjunctive corticosteroid therapy reduces mortality, accelerates clinical recovery or accelerates microbiological recovery in people with pulmonary tuberculosis.


METHODS
We identified studies indexed from 1966 up to May 2014 by searching: Cochrane Infectious Diseases Group's trials register, Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and LILACS using comparative search terms. We handsearched reference lists of all identified studies and previous reviews and contacted relevant researchers, organizations and companies to identify grey literature.


METHODS
Randomized controlled trials and quasi-randomized control trials of recognized antimicrobial combination regimens and corticosteroid therapy of any dose or duration compared with either no corticosteroid therapy or placebo in people with pulmonary tuberculosis were included.


METHODS
At least two investigators independently assessed trial quality and collected data using pre-specified data extraction forms. Findings were reported as narrative or within tables. If appropriate, Mantel-Haenszel meta-analyses models were used to calculate risk ratios.


RESULTS
We identified 18 trials, including 3816 participants, that met inclusion criteria. When compared to taking placebo or no steroid, corticosteroid use was not shown to to reduce all-cause mortality, or result in higher sputum conversion at 2 months or at 6 months (mortality: RR 0.77, 95%CI 0.51 to 1.15, 3815 participants, 18 studies, low quality evidence; sputum conversion at 2 months RR 1.03, 95%CI 0.97 to 1.09, 2750 participants, 12 studies; at 6 months; RR1.01, 95%CI 1.01, 95%CI 0.98 to 1.04, 2150 participants, 9 studies, both low quality evidence). However, corticosteroid use was found to increase weight gain (data not pooled, eight trials, 1203 participants, low quality evidence), decrease length of hospital stay (data not pooled, three trials, participants 379, very low quality of evidence) and increase clinical improvement within one month (RR 1.16, 95% CI 1.09 to 1.24; five trials, 497 participants, low quality evidence).


CONCLUSIONS
It is unlikely that adjunctive corticosteroid treatment provides major benefits for people with pulmonary tuberculosis. Short term clinical benefits found did not appear to be maintained in the long term. However, evidence available to date is of low quality. In order to evaluate whether adjunctive corticosteroids reduce mortality, or accelerate clinical or microbiological recovery in people with pulmonary tuberculosis further large randomized control trials sufficiently powered to detect changes in such outcomes are needed.
Population Health Sciences Institute, St George's, University of London, Cranmer Terrace, London, UK, SW17 0RE.
Julia A
JA
Critchley
Lois C
LC
Orton
Fiona
F
Pearson
D000305:Adrenal Cortex Hormones / Q000009:adverse effects / Q000627:therapeutic use*; D002423:Cause of Death; D017024:Chemotherapy, Adjuvant; D005334:Fever / Q000188:drug therapy; D006801:Humans; D007902:Length of Stay; D016032:Randomized Controlled Trials as Topic; D013256:Steroids / Q000009:adverse effects / Q000627:therapeutic use; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy* / Q000401:mortality; D015430:Weight Gain
D000305:Adrenal Cortex Hormones; D013256:Steroids