Oral steroids for long‐term use in cystic fibrosis New search for studies and content updated (no change to conclusions)

Abstract

Abstract Background

In cystic fibrosis (CF) airway obstruction and recurrent respiratory infection lead to inflammation, long‐term lung damage, respiratory failure and death. Anti‐inflammatory agents, e.g. oral corticosteroids are used since inflammation occurs early in disease. This is an update of a previously published review.

Objectives

To assess the effectiveness of oral corticosteroids in respiratory complications in CF, particularly lung function and adverse events. We examined long‐term use (over 30 days) only.

Search methods

We searched the Cochrane CF and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.

Most recent search: 28 August 2015.

Selection criteria

Randomised trials comparing oral corticosteroids given for more than 30 days with placebo or no additional therapy in people with CF.

Data collection and analysis

Two authors independently assessed study eligibility and quality.

Main results

Of eleven studies identified, three (354 participants) were included: two with four‐year follow up and one with 12‐weeks follow up. Data were lacking on predefined outcomes; common outcomes were examined at different time‐points and presented differently. Meta‐analyses were not possible.

In one study, oral corticosteroids at prednisolone‐equivalent dose of 1 mg/kg alternate days slowed progression of lung disease; at two and four years, % predicted FEV1 in the 1 mg/kg group changed significantly more than in the placebo group (P < 0.02). During the first two years, the 2 mg/kg group was not significantly different from the placebo group. Linear growth retardation was observed from six months in the 2 mg/kg alternate days prednisolone group and from 24 months in the 1 mg/kg alternate days prednisolone group.

Adverse events terminated one four‐year study early. Year 10 follow up showed catch‐up growth started two years after treatment ceased. Alternate‐day treatment with oral corticosteroids may have impaired growth until adulthood in boys.

Authors' conclusions

Oral corticosteroids at prednisolone‐equivalent dose of 1 to 2 mg/kg alternate days appear to slow progression of lung disease in CF; benefit should be weighed against occurrence of adverse events. Risk‐benefit analysis of low‐dose alternate days corticosteroids is important. No further trials of this intervention are anticipated, and hence the review will no longer be regularly updated. However, if any new data are published, these will be incorporate when available.

Author(s)

Katharine Cheng, Deborah Ashby, Rosalind L Smyth

Abstract

Plain language summary

Use of oral steroids for cystic fibrosis

Cystic fibrosis causes frequent lung infection and the airways become blocked with mucus. This in turn leads to inflammation, which causes more lung damage and more mucus to be produced. Corticosteroids are strong drugs given to treat this inflammation. The review includes three trials; one for 12 weeks and two with four‐year follow up. We could not combine any data. Trials showed that oral steroids of 1mg/kg to 2 mg/kg (prednisolone equivalent) given every other day seemed to slow the advance of lung disease. However, there are serious adverse effects such as cataracts and the slowing of growth at the higher dose. These led to one trial stopping early. Follow‐up data show that catch‐up growth started two years after treatment ceased. Treatment must use the lowest effective dose and the shortest duration of therapy to reduce the risk of a permanent effect on growth. A dose of 1 mg/kg on alternate days might be considered for up to 24 months, but close attention should be paid to adverse effects. We do not expect any further trials of this treatment to be undertaken, so we do not plan to continue to regularly update the review. However, if any new information is published, we will include this when it is available. This is an update of a previously published review.

Author(s)

Katharine Cheng, Deborah Ashby, Rosalind L Smyth

Reviewer's Conclusions

Authors' conclusions

Implications for practice

Current evidence suggests that oral corticosteroids at a prednisolone equivalent dose of 2 mg/kg on alternate days is effective but should not be used due to the high risk of occurrence of important side effects. A dose of 1 mg/kg on alternate days might be considered for up to 24 months but close attention to the occurrence of adverse effects is warranted.

Implications for research

Although oral corticosteroids at a dose of 1 mg/kg to 2 mg/kg on alternate days appear to slow the progression of lung disease in CF, this is at the expense of the occurrence of adverse events. The evidence from Eigen's study suggests that growth retardation may appear after 24 months of treatment with prednisolone at 1 mg/kg on alternate days and as early as six months with a dose of 2 mg/kg on alternate days (Eigen 1995). Therefore, further RCTs examining the effectiveness and safety of treatment on a long‐term basis are not warranted. However, a survival analysis from the 10‐year follow‐up study (Auerbach 1985) or indeed from the other long‐term study (Eigen 1995) would be helpful in determining whether the use of oral corticosteroids has any effect on long‐term survival. It would seem prudent to address the effectiveness of alternative anti‐inflammatory agents in future RCTs.

We recommend that any future studies should adequately consider adverse effects particularly quality of life measures to assess acceptability to participants. We would urge trialists to recognise that the results of individual RCTs are likely to be included in systematic reviews such as this. They should therefore consider standardising the presentation of outcomes to enable the data to be aggregated. However, despite these recommendations, we do not anticipate any further trials of this intervention, and hence we do not plan to update the review on a regular basis. If we become aware that any new data have been published, we will incorporate these into the review.

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