Combination therapy in asthma--fixed or variable dosing in different patients?

Abstract

The introduction of combination products, for the coadministration of an inhaled corticosteroid (ICS) with a long-acting beta2-agonist in a single inhaler, has greatly simplified asthma therapy. The two combination inhalers currently available, Symbicort (budesonide/formoterol in a single inhaler) and Seretide (salmeterol/fluticasone), comply with Step 3 of international guidelines that recommend the addition of a long-acting beta2-agonist to ICS in patients who are inadequately controlled on ICS alone. Importantly, combination inhalers ensure that patients cannot neglect their ICS maintenance therapy in favour of the long-acting beta2-agonist--which may improve adherence and overall asthma control. In vitro experiments suggest that ICS and long-acting beta2-agonists may interact beneficially when they are administered via one inhaler. The efficacy and tolerability of budesonide/formoterol and salmeterol/fluticasone have been demonstrated. There are currently two approaches for treating asthma using combination therapy--fixed and adjustable dosing. Fixed dosing with budesonide/formoterol or salmeterol/fluticasone provides effective asthma control in line with guideline goals. However, given the inherent variability of asthma, there is increasing evidence that adjusting the dose of ICS according to fluctuations in symptoms is beneficial. Findings from a series of studies comparing fixed and adjustable symptom-guided dosing regimens demonstrate that adjustable dosing may improve asthma control at an overall lower steroid dose. Ultimately, if adjustable dosing proves to be an effective treatment option, it may be possible to use budesonide/formoterol for both maintenance therapy and symptom relief, thereby overcoming the need for a separate reliever inhaler. This is because formoterol has a more rapid onset and greater dose-related effects than salmeterol in salmeterol/fluticasone. Given that all patients are different, with different disease severities and treatment preferences, both fixed and adjustable dosing strategies are likely to be important in the long-term management of asthma. It is possible that different treatment options will be used for different patients, depending on their disease severity, personality and ability to adhere to therapy.