X2.2.2 Systemic corticosteroids for treatment of exacerbations

Systemic corticosteroids reduce the severity of and shorten recovery from exacerbations (Walters 2014a) [evidence level I].

Walters et al report that there is high-quality evidence that systemic corticosteroids reduce treatment failure (defined as additional treatment, hospital admission/re-admission for index episode, return to emergency department, unscheduled physician visit for the index episode), improve lung function, shorten recovery and reduce the severity of exacerbations of COPD (Walters 2014a) [evidence level I]. Systemic corticosteroids reduced the risk of treatment failure by over half compared with placebo in nine studies (n = 917) with median treatment duration 14 days, odds ratio (OR) 0.48 (95% confidence interval (CI) 0.35 to 0.67. The number needed to treat to avoid one treatment failure is 9. There is no evidence that treatment with corticosteroids alters mortality.

Unlike earlier reviews this review included four papers that compared intravenous corticosteroids with oral corticosteroids and two papers with ventilated patients in ICU. In patients requiring ventilation in ICU, pooled data did not show a reduction in length of stay, duration of ventilation or mortality in those receiving corticosteroids compared with placebo (Walters 2014a). Walters et al concluded that there is no evidence of benefit for intravenous treatment compared with oral treatment with corticosteroids on treatment failure, relapse or mortality. Hyperglycaemia rates were higher with intravenous corticosteroids.

With regards to duration of treatment, a meta-analysis by Walters et al (Walters 2014b) concluded that a shorter course of corticosteroids (around 5 days) is unlikely to lead to worse outcomes compared with a longer course. In 2013, Leuppi et al (Leuppi 2013) reported on the largest randomised controlled trial in this area. The authors found that a five day course of corticosteroids (one 40mg dose of intravenous methylprednisolone followed by four days of prednisolone 40mg) was non-inferior to treatment for 14 days (one IV dose plus 13 days of 40 mg prednisolone) regarding subsequent exacerbations and mortality over six months of follow-up.

In light of the evidence above, it would appear that a 5 day course of oral prednisolone of 30mg to 50mg is adequate. In patients who have been on oral corticosteroids for longer than 14 days, tapering may be necessary. Patients on long-term oral corticosteroid therapy (> 7.5 mg prednisolone daily for more than 6 months) are at risk of developing osteoporosis. Prevention and treatment of corticosteroid-induced osteoporosis should be considered.

There is emerging evidence that blood eosinophil levels can be used as a biomarker to determine which patients require oral corticosteroids for exacerbations of COPD.  A small, single centre, double blind randomised controlled trial used blood eosinophils as a biomarker to determine if prednisolone would be given for an exacerbation of COPD.  In the intervention arm only patients with blood eosinophils above 0.2% received prednisolone.  In the standard arm all patients received prednisolone.   The prednisolone dose was 30mg for 14 days and both groups received oral antibiotics.  There was no difference in treatment failure or health status between the biomarker and standard groups (Bafadhel 2012). Bafadhel re-analysed data from 3 additional randomised control trials that examined the use of oral corticosteroids in COPD exacerbations (n=243) (Bafadhel 2014). Patients had blood eosinophil levels measured at the time of COPD exacerbation. Blood eosinophils >2% were a useful biomarker to determine which patients benefit from systemic corticosteroids. The trial designs had considerable heterogeneity. Further, larger studies with long term follow up are required before any firm recommendations can be made.