Steroid therapy appears to be associated with increased risk of mortality among patients with acute exacerbation of fibrotic ILD and should therefore be used judiciously with consideration of other precipitating factors, Australian researchers say.
Based on data in 107 local patients, the findings challenge the current paradigm that exacerbations of all fibrotic ILD should be treated with immunosuppression, they argue.
Their study involved 10 years’ worth of patients from the Alfred and Box Hill hospitals in Melbourne experiencing acute exacerbations of fibrotic ILD, 43% of whom received acute steroid treatment.
Review of medical records showed steroid use was associated with a four times increased risk of inpatient mortality or transplantation. Those patients receiving steroids also had a significantly reduced median survival of 221 days post index admission, versus 521 days in the non-steroid group, the researchers reported in Respirology (link here).
“This retrospective cohort study suggests that steroid use in patients with acute exacerbation of fibrotic ILD may not reduce inpatient mortality and, in fact, may be potentially associated with increased risk of death or transplant although there are several additional factors that may have contributed to this,” they wrote.
“Clinicians should consider other precipitating factors for exacerbations and use steroids judiciously.”
The team noted that pre-admission FVC and DLCO were similar in both the steroid and non-steroid group, as were distribution of diagnoses and smoking history. On the other hand, the steroid cohort was of younger age with fewer comorbidities, but had higher oxygen requirements.
Of some note, among the steroid group, there appeared to be a reduced risk of all-cause mortality in non-IPF patients compared to their IPF counterparts.
This demonstrated a “potential signal for survival benefit” in these patients, but further study was required to ascertain whether specific non-IPF ILD cohorts were more likely to benefit from steroids compared with others, they said.
“An emerging topic of interest amongst clinicians and researchers is whether the presence of progressive fibrosis, regardless of the underlying cause of ILD, represents a unique disease phenotype requiring its own approach to treatment of AE,” they wrote.
The authors noted recently updated guidelines continued to include a weak recommendation for corticosteroid treatment, based upon the predicate that fibroblastic formation was mediated by inflammatory cytokines.
However, while corticosteroids had long been considered effective anti-inflammatory agents, emerging evidence indicated that up-regulation of certain cytokines in IPF affected lung tissue may negate the anti-inflammatory effect of corticosteroids thereby resulting in lack of clinical response, they said.
Beyond that was a possible role of lung and gut microbiota in influencing AEs and progression of fibrosis, which could be impacted by steroids, according to the team.
“AE-FILD is a rare clinical event, hampering traditional prospective trial design. Our study raises the question of whether there is a meaningful benefit to derive from steroid therapy (in some cases at doses as high as 23 mg prednisolone-equivalent/kg/day) in all AE-FILD cases or whether, in fact, phenotypic and endotypic features can be recognized that predict for steroid responsiveness,” they added.
“It is likely that only through international collaboration using novel clinical trial platforms and adaptive trial design, such as that proposed by the recently established REMAP-ILD collaboration, that prospective research of sufficient sample size will be achieved.”