Drug treatments

Corticosteroids (inhaled)

In this section:

Key points | Benefits and Harms | Comment

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Key points

  • For GRADE evaluation of interventions for COPD, see table.
  • Inhaled corticosteroids reduce exacerbations in COPD and reduce decline in FEV1, but the beneficial effects are small.
  • Combined inhaled corticosteroids plus long-acting beta2 agonists improve lung function and symptoms and reduce exacerbations compared with placebo, and may be more effective than either treatment alone.
  • Long-term treatment with inhaled corticosteroids may predispose to adverse effects such as skin bruising, oral candidiasis, and pneumonia.
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Benefits and harms

Inhaled corticosteroids (short-term treatment) versus placebo:

We found one systematic review (search date 2007).[58]

Lung function and exercise capacity

Compared with placebo Inhaled corticosteroids (short-term treatment) seems no more effective at improving FEV1 in people with moderate to severe COPD (moderate-quality evidence).

Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect size (for ORs and RRs)Favours
Lung function

[58]

Systematic review

424 people with COPD

5 RCTs in this analysis

Change in pre-bronchodilator FEV1, 2 to 6 months

inhaled corticosteroid

placebo

Absolute numbers not reported

WMD 0.06 L

95% CI 0.03 to 0.09

P = 0.0002

A statistically significant, but modest effect

not-calculated

inhaled corticosteroid

Mortality

No data from the following reference on this outcome.[58]

COPD exacerbation and worsening of symptoms

No data from the following reference on this outcome.[58]

Quality of life

No data from the following reference on this outcome.[58]

Adverse effects

No data from the following reference on this outcome.[58]

Inhaled corticosteroids (long-term treatment) versus placebo:

We found 6 systematic reviews (search dates 2001,[59] 2002,[60]2003,[29] 2007,[58] and 2008[61][62]), and 3 additional RCTs.[63][64][35]

Mortality

Compared with placebo Inhaled corticosteroids (long-term treatment) seem no more effective at reducing mortality at 3 years in people with moderate to severe COPD (moderate-quality evidence).

Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect size (for ORs and RRs)Favours
Mortality

[62]

Systematic review

9223 people with COPD

5 RCTs in this analysis

All-cause mortality, 12 months

128/4636 (2.8%) with inhaled corticosteroids

148/4597 (3.2%) with placebo

RR 0.86

95% CI 0.68 to 1.09

P = 0.2

not-significant

not significant

[35]

RCT

4-armed trial

6184 people with COPD; 6112 people included in efficacy analysis

Other comment

The third and fourth arms assessed salmeterol 50 micrograms once daily plus fluticasone 500 micrograms twice daily and salmeterol alone (50 micrograms twice daily)

Mortality, 3 years

246/1534 (16%) with fluticasone (500 micrograms twice daily)

231/1524 (15%) with placebo

Other comment

3096 people in analysis

Analysis included people who had discontinued study medication

HR 1.06 (fluticasone v placebo)

95% CI 0.89 to 1.27

P = 0.53

not-significant

not significant

No data from the following reference on this outcome.[59][60][29][58][61][63][64]

Lung function and exercise capacity

Compared with placebo Inhaled corticosteroids (long-term treatment) seem more effective at improving FEV1 in people with moderate to severe COPD (moderate-quality evidence).

Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect size (for ORs and RRs)Favours
Lung function

[58]

Systematic review

2333 people with COPD

4 RCTs in this analysis

Reduction in annual decline in FEV1, at least 2 years

inhaled corticosteroids

placebo

Absolute numbers not reported

Other comment

People without bronchodilator response or bronchial hyperresponsiveness

+5.8 mL/year

95% CI –0.28 mL/year to +11.9 mL/year

P >0.05

not-significant

not significant

[63]

RCT

4-armed trial

691 people

Other comment

The third and fourth arms assessed combination treatment with inhaled corticosteroids plus long-acting beta2 agonist, and inhaled beta2 agonists alone

Improvement in FEV1, 6 months

fluticasone (500 micrograms)

placebo

Absolute results not reported

Difference in FEV1: 105 mL (fluticasone v placebo)

P <0.05

not-calculated

fluticasone

[64]

RCT

4-armed trial

723 people

Other comment

The third and fourth arms assessed combination treatment with inhaled corticosteroids plus long-acting beta2 agonist, and inhaled beta2 agonists alone

Increase in post-dose FEV1 from baseline, 6 months

147 mL with fluticasone

58 mL with placebo

P <0.05 (fluticasone v placebo)

not-calculated

fluticasone

No data from the following reference on this outcome.[59][60][29][61][62][35]

COPD exacerbation and worsening of symptoms

Compared with placebo Inhaled corticosteroids (long-term treatment) seem more effective at improving dyspnoea and at reducing COPD exacerbations in people with moderate to severe COPD (moderate-quality evidence).

Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect size (for ORs and RRs)Favours
COPD exacerbations

[61]

Systematic review

8164 people with COPD

11 RCTs in this analysis

Risk of COPD exacerbation, 1 to 4.5 years

inhaled corticosteroid

placebo

Absolute numbers not reported

RR 0.82

95% CI 0.73 to 0.92

P <0.05

Sensitivity analysis suggested that there was benefit only in people with severe disease (FEV1 <50%)

small

inhaled corticosteroids

Symptom severity

[63]

RCT

4-armed trial

691 people

Other comment

The third and fourth arms assessed combination treatment with inhaled corticosteroids plus long-acting beta2 agonist, and inhaled beta2 agonists alone

Improvement in transitional dyspnoea index (TDI), 6 months

fluticasone (500 micrograms)

placebo

Absolute results not reported

Difference in TDI 1.0

P <0.05

not-calculated

fluticasone

[64]

RCT

4-armed trial

723 people

Other comment

The third and fourth arms assessed combination treatment with inhaled corticosteroids plus long-acting beta2 agonist, and inhaled beta2 agonists alone

Mean TDI score, 6 months

1.7 with fluticasone

1.0 with placebo

Other comment

363 people in this analysis

P = 0.057

not-significant

not significant

No data from the following reference on this outcome.[59][60][29][58][62][35]

Quality of life

Compared with placebo Inhaled corticosteroids (long-term treatment) seem more effective at improving health-related quality of life in people with COPD (moderate-quality evidence).

Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect size (for ORs and RRs)Favours
Health-related quality of life

[58]

Systematic review

2507 people with COPD

5 RCTs in this analysis

Rate of change in St George's Respiratory Questionnaire (SGRQ), per year

inhaled corticosteroids

placebo

Absolute numbers not reported

Other comment

Analysis in "long-term" studies, but long term not further specified

WMD –1.22 units/year

95% CI –1.83 units/year to –0.60 units/year

P >0.05

not-significant

not significant

[64]

RCT

4-armed trial

723 people

Other comment

The third and fourth arms assessed combination treatment with inhaled corticosteroids plus long-acting beta2 agonist, and inhaled beta2 agonists alone

Improvement in Chronic Respiratory Disease Questionnaire (CRQ) score from baseline, 6 months

10.4 with fluticasone

5.0 with placebo

Other comment

363 people in this analysis

P = 0.002

not-calculated

fluticasone

No data from the following reference on this outcome.[59][60][29][61][62][63][35]

Adverse effects
Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect size (for ORs and RRs)Favours
Adverse effects

[59]

Systematic review

3976 people

9 RCTs in this analysis

Other comment

RCTs were of at least 6 months' duration

Oropharyngeal candidiasis

inhaled corticosteroids

placebo

Absolute results not reported

RR 2.1

95% CI 1.5 to 3.1

moderate

placebo

[29]

Systematic review

5562 people with stable moderate to severe COPD

6 RCTs in this analysis

Other comment

5 RCTs were also identified by a review[59] with an earlier search date

Oral thrush

inhaled corticosteroids

placebo

Absolute results not reported

RR 2.98

95% CI 2.09 to 4.26

moderate

placebo

[29]

Systematic review

3772 people with stable moderate to severe COPD

4 RCTs in this analysis

Other comment

5 RCTs were also identified by a review[59] with an earlier search date

Dysphonia

inhaled corticosteroids

placebo

Absolute results not reported

RR 2.02

95% CI 1.43 to 2.83

moderate

placebo

[58]

Systematic review

3864 people with stable, moderate to severe COPD

4 RCTs in this analysis

Bruising

inhaled corticosteroids

placebo

Absolute numbers not reported

OR 1.86

95% CI 1.39 to 2.48

P <0.05

small

placebo

[29]

Systematic review

1867 people with stable moderate to severe COPD

2 RCTs in this analysis

Other comment

5 RCTs were also identified by a review[59]with an earlier search date

Cataracts

inhaled corticosteroids

placebo

Absolute results not reported

RR 1.05

95% CI 0.84 to 1.31

not-significant

not significant

[29]

Systematic review

972 people with stable moderate to severe COPD

Data from 1 RCT

Other comment

5 RCTs were also identified by a review[59] with an earlier search date

Reduction in bone mineral density (BMD) (femoral neck and lumbar spine), over 3 to 4 years

inhaled triamcinolone

placebo

Absolute results not reported

Reduction in BMD in femoral neck with triamcinolone compared with placebo: 1.57%

95% CI 2.40% to 0.74%

Reduction in BMD in lumbar spine with triamcinolone compared with placebo: 1.07%

95% CI 1.86% to 0.28%

not-calculated

placebo

[29]

Systematic review

972 people with stable moderate to severe COPD

Data from 1 RCT

Other comment

5 RCTs were also identified by a review[59] with an earlier search date

Excess risk of fractures, 3 years

inhaled triamcinolone

placebo

Absolute results not reported

RR 0.70

95% CI 0.36 to 1.37

not-significant

not significant

[62]

Systematic review

8131 people with COPD

In review [57]

3 RCTs in this analysis

Fracture risk, 3 years

195/4073 (4.8%) with inhaled corticosteroid

178/4058 (4.4%) with placebo

Absolute numbers not reported

RR 1.09

95% CI 0.89 to 1.33

P = 0.4

not-significant

not significant

[60]

Systematic review

Number of people and RCTs in analysis not reported

Other comment

Review identified 12 RCTs (5775 people with COPD) of at least 6 months' duration

7 RCTs were also identified by one review,[59] and 5 RCTs were identified by another review[29]

Proportion of people withdrawing from study because of adverse effects, mean follow-up of 20 months

inhaled corticosteroids

placebo

Absolute results not reported

RR 0.92

95% CI 0.74 to 1.14

not-significant

not significant

[63]

RCT

4-armed trial

691 people

Other comment

The remaining arms assessed combination treatment with inhaled corticosteroids plus long-acting beta2 agonist, and inhaled beta2 agonists alone

Oropharyngeal candidiasis, 6 months

10% with fluticasone (500 micrograms)

<1% with placebo

Absolute numbers not reported

P value not reported

[64]

RCT

4-armed trial

723 people

Other comment

The remaining arms assessed the effects of combination treatment with inhaled corticosteroids plus long-acting beta2 agonists, and inhaled beta2 agonists alone

Rate of serious adverse effects, 6 months

5% with fluticasone

5% with placebo

Absolute numbers not reported

Other comment

Rates reported to be about 5%

P value not reported

[64]

RCT

4-armed trial

723 people

Other comment

The remaining arms assessed combination treatment with inhaled corticosteroids plus long-acting beta2 agonists, and inhaled beta2 agonists alone

Rate of adverse effects leading to withdrawal of treatment, 6 months

5% with fluticasone

5% with placebo

Absolute numbers not reported

Other comment

No further data reported

P value not reported

[35]

RCT

4-armed trial

6184 people with COPD; 6112 people included in efficacy analysis

Other comment

The remaining arms assessed salmeterol 50 micrograms once daily plus fluticasone 500 micrograms twice daily and salmeterol alone (50 micrograms twice daily)

Proportion of people experiencing a drug-related adverse effect, 3 years

19% with fluticasone (500 micrograms twice daily)

13% with placebo

Absolute numbers not reported

Other comment

3096 people in analysis

Analysis included people who had discontinued study medication

The most common adverse effect reported was COPD exacerbation

Significance not assessed

No data from the following reference on this outcome.[61]

Inhaled corticosteroids alone versus inhaled corticosteroids plus beta2 agonists:

See option on inhaled corticosteroids plus beta2 agonists.

Further information on studies

[35]The RCT also carried out a last observation carried forward analysis for the outcome of FEV1. However, the withdrawal rate from the RCT was high and the proportion of people followed up at 3 years for this outcome was 56% (851/1524) in the placebo group and 62% (947/1534) in the fluticasone alone group. These do not meet Clinical Evidence follow-up reporting criteria of 80%, and so these data are not reported here.

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Comment

Clinical guide:

Many of the RCTs of inhaled corticosteroids have been done in people with moderate to severe COPD (FEV1 <50% predicted) and hence apply only to that population. The lifetime risk of fractures in people who take corticosteroids for longer than 3 to 4 years is unknown. The Global Initiative on Obstructive Pulmonary Disease has therefore advocated the use of inhaled corticosteroids only in people with an FEV1 <50% predicted, and frequent exacerbations (at least 3 exacerbations in the past 3 years).[1]