Management of stable chronic obstructive pulmonary disease in primary and secondary care: summary of updated NICE guidance

According to the article on the new updated NICE guidelines for COPD
it gives “an evidence based rationale for the sequencing of inhaled drugs
used singly and in combination according to persistence of symptoms,
exacerbations, and severity of airflow obstruction and clarifies options
for escalating inhaled treatment according to whether FEV1 is above or
below 50%”. It goes on further to say that this bit of guidance is “based
on very low to moderate quality evidence from randomised controlled
trials, cost effectiveness evidence, and the experience and opinion of the
guideline development group”.[1]

The problem with this statement and the guidance on using these drugs
is that there are very good randomised controlled study data to show that
inhaled corticosteroids, either alone, or in combination with long-acting
beta-2 agonists, do not work to modify disease, for example, slowing
decline in FEV1, and at most, only have modest effects on improving
quality of life.[2] Take the main example, the inaptly named “TOwards a
Revolution in COPD Health (TORCH Study).[3] This was a large, 6,112
patient study in COPD and did not demonstrate benefit from the inhaled
corticosteroid, fluticasone combined with the long-acting beta-2 agonist,
salmeterol compared with placebo or salmeterol or fluticasone alone over
three years. TORCH was negative for the primary outcome of all cause
mortality. A secondary outcome of change in quality of life (‘health
status’) measures did not reach the predetermined level of clinical
significance, a fact seemingly overlooked when it was published. This is
not an absence of evidence but a clear evidence of absence of effect.
TORCH and some other studies do provide limited evidence that inhaled
corticosteroids reduce exacerbations in COPD (another secondary outcome)
defined by episodes of need for antibiotics or oral steroids but this has
limited clinical significance; in TORCH the combination did not prevent
hospitalisation from exacerbations compared with salmeterol alone.[3]

Put alongside clear evidence that inhaled corticosteroids cause harm
in the form of pneumonia, which the updated guideline acknowledges, “Be
aware of the potential risk of developing side effects (including non-
fatal pneumonia) in people with COPD treated with inhaled corticosteroids
and be prepared to discuss with patients.”, this begs the questions, why
do we spend millions on these drugs, and why do guideline developers
choose to ignore or downplay this evidence of no or minimal benefit? Do
they “see what they want to see”, as has happened in other disease areas?
Do clinicians and patients realise the limitations of the evidence
supporting these recommendations?

[1] O’Reilly J, Jones MM, Parnham J, et al. Guidelines: Management of
stable chronic obstructive pulmonary disease in primary and secondary
care: summary of updated NICE guidance. BMJ 2010;340:c3134

[2] Yang IA, Fong K, Sim EH A, Black PN, Lasserson TJ. Inhaled
corticosteroids for stable chronic obstructive pulmonary disease. Cochrane
Database of Systematic Reviews 2007, Issue 2. Art. No.: CD002991. DOI:
10.1002/14651858.CD002991.pub2

[3] Calverley PMA, Anderson JA, Celli B, et al. Salmeterol and
fluticasone propionate and survival in chronic obstructive pulmonary
disease. N Engl J Med 2007;356:775–89.

[4] McCormack J, Greenhalgh T. Seeing what you want to see in
randomised controlled trials: versions and perversions of UKPDS data.
United Kingdom prospective diabetes study. BMJ 2000;320:1720-3.

Competing interests:
None declared