Minimum maintenance dose required in asthma
Peak expiratory flow rates improved more for patients treated using a stable maintenance therapy dose |
A minimum daily amount of maintenance therapy is required to prevent exacerbations in adults with persistent asthma, results from a new study suggest.
Mark FitzGerald of Vancouver General Hospital, and colleagues, conducted
a trial involving 688 patients, each of whom received both active drug
and placebo delivered via dry powder inhalers. The trial compared two
treatment strategies: a stable dose of salmeterol/fluticasone proprionate
50/250µg via Diskus and an adjustable maintenance dose of formoterol/budesonide
6/200µg via Turbohaler.
During the 52-week treatment period, patients received either salmeterol/fluticasone
one puff twice daily or formoterol/budesonide two puffs twice daily,
for four weeks. Following this, the dose of the Diskus (salmeterol/fluticasone
proprionate or placebo) remained constant. Patients who met specified
symptom-control criteria were instructed to reduce the Turbohaler (formoterol/budesonide
or placebo) to one puff twice daily, and subsequently to one puff daily
as per the datasheet for Symbicort (formoterol/budesonide). If these
criteria were not met at a later clinic visit the dose reverted back
to one puff twice daily.
If asthma became uncontrolled patients could increase the Turbohaler
to four puffs twice daily for seven to 14 days according to a self-management
plan. If this was unsuccessful a course of oral corticosteroids was prescribed.
The researchers found that stable dosing with salmeterol/fluticasone
resulted in greater improvements in the percentage of symptom-free days
(P=0.034), percentage of days free of rescue medication (P=0.008) and
morning peak expiratory flow (P=0.006).
In addition, stable dosing almost halved the number of exacerbations
requiring oral corticosteroids or hospital visits. The researchers acknowledge
that the adjustable maintenance dose approach led to less maintenance
treatment being used and that improvements in all parameters were seen
in this group. They suggest that regular low amounts of maintenance therapy
can be effective. However, they say: “A higher daily amount of
maintenance treatment may afford greater protection against the triggers
that can result in the type of exacerbations requiring interventions
with oral corticosteroids or hospital care.”
The study is published online (PDF 230K)
in Clinical Therapeutics.
Anna Murphy, consultant respiratory pharmacist, Glenfield Hospital, Leicester,
told The Journal: “The results of the study need to be interpreted
carefully since it contradicts the findings of eight other studies investigating
adjustable maintenance dosing with Symbicort.”
She noted that the dosage of Symbicort administered to patients for most
of the time was less than in other trials (1.8 puffs 200/6 Symbicort
each day compared with 3.4 puffs a day in an earlier study). “This
suggests that patients were effectively under-dosed and this may be responsible
for the increase in exacerbation rate reported with Symbicort,” she
added.
AstraZeneca, manufacturer of Symbicort, said the study’s design
led to an unfair comparison between Symbicort and Seretide. “In
everyday clinical practice, less than 0.3 per cent of patients on Symbicort
adjustable dosing are maintained on one inhalation per day,” the
company stated. |
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Pharmaceutical Journal
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