Outcomes in idiopathic pulmonary fibrosis: a meta-analysis from placebo controlled trials.
BACKGROUND
Most data on outcomes in Idiopathic Pulmonary Fibrosis (IPF) pre-dates current guidelines. Data on rates of infection is sparse; the effect of low-dose corticosteroids and disease severity is unknown.


METHODS
We identified randomised-controlled trials of IPF and analysed rates of mortality, lower respiratory tract infections (LRTIs), IPF progression and acute exacerbations from the placebo arms. We standardised event rates and compared differences using incidence rate ratios (IRRs) between subgroups according to disease severity or use of low-dose immunosuppression.


RESULTS
Mortality was lower in trials that recruited patients with mild-moderate disease severities only, as compared to trials where patients with severe disease were allowed (188.6 vs 78.6 deaths per 1000 patient/years, IRR 0.30-0.59, p < 0.0001). No statistical difference was seen between trials permitting and excluding low-dose prednisolone use. LRTIs were found to be commoner in trials allowing low dose prednisolone use compared with those that did not (227.1 vs 63.4 infections per 1000 patient/years. IRR 2.56-5.13, p < 0.0001), and were less frequent in trials excluding patients with severe disease (153.9 vs 257.8 infections per 1000 patient/years, IRR 0.45-0.81, p = 0.0003). Acute exacerbations occurred less frequently in trials excluding severe disease (28.2 vs 122.9 exacerbations per 1000 patient/years, IRR 0.11-0.55, p < 0.0001). There was no difference between groups in rates of IPF progression.


CONCLUSIONS
Mortality is heterogeneous and dependent on entry criteria. Infection rates were high, both with and without immunosuppression, and were higher in severe disease. Consideration should be given to alternative outcomes to mortality in future IPF trials if severe disease is excluded.
Norfolk and Norwich University Hospital, Colney Lane, Norwich, Norfolk NR4 7UY, UK. Electronic address: christopher.atkins@nnuh.nhs.uk.
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Atkins
Norfolk and Norwich University Hospital, Colney Lane, Norwich, Norfolk NR4 7UY, UK; Norwich Medical School, University of East Anglia, Norwich, Norfolk NR4 7TJ, UK.. Electronic address: y.loke@uea.ac.uk.
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Loke
Norfolk and Norwich University Hospital, Colney Lane, Norwich, Norfolk NR4 7UY, UK; Norwich Medical School, University of East Anglia, Norwich, Norfolk NR4 7TJ, UK.. Electronic address: a.m.wilson@uea.ac.uk.
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Wilson
D000368:Aged; D018450:Disease Progression; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000188:drug therapy / Q000401:mortality*; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D016032:Randomized Controlled Trials as Topic; D012141:Respiratory Tract Infections / Q000139:chemically induced; D016896:Treatment Outcome
D007166:Immunosuppressive Agents
Idiopathic pulmonary fibrosis; Lung diseases, interstitial; Meta-analysis