C P Atkins1, Y K Loke2, A M Wilson3. 1. Norfolk and Norwich University Hospital, Colney Lane, Norwich, Norfolk NR4 7UY, UK. Electronic address: christopher.atkins@nnuh.nhs.uk. 2. 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. 3. 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.
Abstract
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. CONCLUSION: 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.
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. CONCLUSION: 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.
Authors: Andrew M Wilson; Allan B Clark; Tony Cahn; Edwin R Chilvers; William Fraser; Matthew Hammond; David M Livermore; Toby M Maher; Helen Parfrey; Ann Marie Swart; Susan Stirling; David R Thickett; Moira Whyte Journal: JAMA Date: 2020-12-08 Impact factor: 56.272
Authors: Maya M Juarez; Andrew L Chan; Andrew G Norris; Brian M Morrissey; Timothy E Albertson Journal: J Thorac Dis Date: 2015-03 Impact factor: 2.895
Authors: Jaana Kaunisto; K Kelloniemi; E Sutinen; U Hodgson; A Piilonen; R Kaarteenaho; R Mäkitaro; M Purokivi; E Lappi-Blanco; S Saarelainen; H Kankaanranta; A Mursu; M Kanervisto; E-R Salomaa; M Myllärniemi Journal: BMC Pulm Med Date: 2015-08-19 Impact factor: 3.317