Salmeterol/fluticasone may not raise COPD survival
New data suggest that the use of salmeterol and fluticasone combination therapy for chronic obstructive pulmonary disease (COPD) does not improve survival but does reduce exacerbations and improves health status and lung function compared with placebo (New England Journal of Medicine 2007;356:775).
The TORCH (towards a revolution in COPD health) study involved 6,112
patients with COPD and an FEV1<60 per cent of the predicted value,
who were randomised to receive salmeterol 50mg plus fluticasone propionate
500mg twice daily, fluticasone alone, salmeterol alone or placebo for
three years. The primary endpoint was death from any cause.
The researchers found that the reduction in mortality in the combination
therapy group, compared with the placebo group, did not reach statistical
significance (hazard ratio 0.825, 95 per cent confidence interval 0.681–1.002;
P=0.052). However, combination therapy did reduce the annual rate of
exacerbations from 1.13 to 0.85 and improved health status and spirometric
values (P<0.001 for all comparisons with placebo).
Pneumonia was reported as an adverse event in more patients receiving
fluticasone than salmeterol or placebo (19.6 per cent in the combination
therapy group, 18.3 per cent in the fluticasone alone group, 13.3 per
cent in the salmeterol alone group and 12.3 per cent in the placebo group).
The researchers acknowledge that it is possible that there is no effect
of combination therapy on mortality but suggest that their study could
have been underpowered to detect this effect. They say that their results
merit further investigation in large, prospective trials. However, they
argue that, until these trials are completed, their data support the
use of salmeterol plus fluticasone in the clinical management of COPD.
The author of an accompanying editorial (ibid, p851)
says that the findings confirm the current position of combination therapy
for patients with
severe COPD with frequent exacerbations but not for patients with milder
disease or without frequent exacerbations. He adds that caution is required
in the use of combination therapy because of the study’s finding
of an increased rate of pneumonia and urges further studies to be undertaken.
Safety
review The use and safety of the two long-acting beta2 agonists
salmeterol and formoterol are currently being reviewed by the Medicines
and Healthcare products
Regulatory Agency. The review is considering their use in both asthma and COPD.
Issues being addressed include how corticosteroid inhalers influence the effects
of formoterol and salmeterol in asthma, whether there is any difference between
formoterol and salmeterol in the way they work, how the clinical effects of formoterol
and salmeterol change with different doses and whether people’s genetic
background significantly affects how they respond to long-acting beta2 agonists.
If significant issues affecting clinical practice are identified at any point,
the MHRA says these will be communicated to health care professionals and patients. |
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