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[The therapeutic index in asthma: how should it be defined?]
N Roche1, C Advenier, G Huchon
1Service de Pneumologie et Réanimation, Hôtel-Dieu, Paris, France. roche_nicolas@hotmail.com
Introduction:
The therapeutic index (efficacy/tolerance or benefit/risk ratio) is a major determinant of treatment decisions in asthma.
Methods:
For the numerator, the therapeutic index depends on efficacy (maximal effect) and not potency (dose-response relationship). With regard to the denominator, several pharmacological factors influence the occurrence of side-effects, the acceptability of which also has to be considered.
Results:
In asthma, some strategies have a more favourable therapeutic index than others;e.g additional treatment (long acting beta2 agonists, leukotriene receptor antagonists, theophylline) to inhaled corticosteroids instead of doubling the dose of the latter. Conversely, it is extremely difficult to compare the therapeutic indices of different molecules of inhaled corticosteroids.
Conclusions:
The potential risk of systemic side effects with long-term administration of high doses of inhaled corticosteroids suggests the need to seek the minimal effective dose.