The higher deposition of drug in the lungs from use of Turbuhaler^® compared with some alternative dry powder inhaler devices is translated into greater clinical efficacy.

This means that lower doses of drug can be used when delivered via Turbuhaler^® compared with some other devices, thus further improving the therapeutic ratio of any product delivered via Turbuhaler^®.

2.1 For inhaled steroids the preferred designs for comparative studies in asthma are important:

Double-blind, placebo-controlled studies involving one of the following:

• A dose-response comparison, in which a dose-response is established for at least one of the drugs (this is because of the shallow dose-response curves of inhaled steroids) and the dose of the other drug is fitted against the dose-response line of the first.
• A dose-down titration comparison, in which well-controlled patients undergo dose reduction until their asthma becomes uncontrolled, at which stage they enter a phase of dose adjustment to determine the minimum effective dose of each drug.
  
  

The importance of using dose-response or dose-reduction studies for comparisons of inhaled corticosteroids has been underlined in an editorial in the European Respiratory Journal. Indeed, it has been decided that single dose comparisons will receive a low priority for publication in the journal (Beasley et al, 2001).

2.2 For inhaled short-acting beta-agonists this is important:

For short-acting beta-agonists caution is needed when interpreting results of studies using a cumulative dose design as the overall bronchodilator response tends to be greater using the cumulative vs. non-cumulative technique (Fishwick et al, 2001). This might be as a result of greater bronchial penetration of later doses after bronchodilation in a cumulative design caused by the initial doses.

In the study by Fishwick et al (2001) a 400 µg cumulative dose of salbutamol produced an almost identical final response as a 800 µg cumulative dose, which suggests that a cumulative design may fail to detect clinical differences between inhalers delivering quite different amounts of drug to the lungs.

Borgström et al (1996) measured lung deposition and function in asthmatic patients receiving terbutaline 0.25 mg and 0.5 mg via Turbuhaler^® and CFC pMDI. Lung deposition was 19.0 and 22.0% for Turbuhaler^® 0.25 and 0.5 mg doses compared with 8.1 and 8.3%, respectively, for the same doses administered via CFC pMDI. The increase in FEV₁ following the 0.25 mg dose was significantly greater when administered via Turbuhaler^® than via CFC pMDI (Figure). No significant differences in FEV₁ were observed between the 0.25 mg Turbuhaler^® dose and the 0.5 mg dose administered via CFC pMDI, indicating that the amount of drug reaching the lungs governs the exerted clinical effect.

Bronchodilator effect of terbutaline 0.25 or 0.5 mg given via Turbuhaler^® or CFC pMDI. The effect of the 0.25 mg dose given by Turbuhaler^® was comparable with that of the higher dose given by pMDI. (Borgström et al, 1996).

Reference

Borgström L, et al. The inhalation device influences lung deposition and bronchodilating effect of terbutaline. Am J Respir Crit Care Med 1996;153:1636-40.

The efficacy of Pulmicort^® Turbuhaler^® and BDP CFC pMDI have been compared in a randomised dose-reduction study in adult asthmatic patients (Brambilla et al, 1994). After a 4-week run-in period, patients were randomised to continue BDP treatment (1000-2000 µg/day) or to receive the same nominal dose of Pulmicort^® Turbuhaler^®. The ICS dose was subsequently reduced at each study visit until asthma control deteriorated. After 3 months, equivalent asthma control was achieved with mean doses of Pulmicort^® Turbuhaler^® 900 µg/day and BDP 1350 µg/day (Figure).

Mean minimal doses producing equal asthma control in adults with asthma (Brambilla et al, 1994).

A dose-response study (Miyamoto et al, 2001) compared the efficacy of Pulmicort^® Turbuhaler^® and BDP CFC pMDI in adult patients with continuing asthma symptoms despite treatment with BDP 200 µg twice daily. After a 2-week run-in period on this treatment, the patients were randomized to continue BDP therapy or to receive Pulmicort^® Turbuhaler^® 100 or 400 µg twice daily for 6 weeks. Pulmicort^® Turbuhaler^® 100 µg twice daily was at least as effective as BDP 200 µg twice daily, and Pulmicort^® Turbuhaler^® 400 µg twice daily was significantly more effective than both of the other treatments.

Read more about the relation between Pulmicort^® Turbuhaler^® and other inhaled steroids

References

Brambilla C, et al. A 3-month comparative dose-reduction study with inhaled beclomethasone dipropionate and budesonide in the management of moderate to severe adult asthma. Drug Invest 1994;8:49-56.

Miyamoto T, et al. Efficacy of budesonide Turbuhaler compared with beclomethasone dipropionate pMDI in Japanese patients with moderately persistent asthma. Respirology 2001;6:27-35.

A randomised dose down-titration study compared the efficacy of Pulmicort^® Turbuhaler^® and fluticasone Diskhaler™ in 217 children with moderate asthma (Agertoft and Pedersen, 1997). After a 2-week run-in period, the children were randomised to receive half this dose of either Pulmicort^® Turbuhaler^® or fluticasone Diskhaler™ for 5 weeks; if there was no deterioration in asthma control over this period, the dose was further reduced by 50% at 5-week intervals until asthma control deteriorated (as judged from diary card variables and exercise testing). The mean minimal effective dose was 212 µg/day for Pulmicort^® Turbuhaler^® and 198 µg/day with fluticasone Diskhaler™ (Figure); there was no significant difference in clinical efficacy between these doses.

Minimal effective doses in a comparative study of Pulmicort^® Turbuhaler^® and fluticasone Diskhaler™ in childhood asthma (Agertoft and Pedersen, 1997).

This means that similar doses of Pulmicort^® Turbuhaler^® and fluticasone Diskhaler™ could be used despite the fact that fluticasone has higher affinity on the GCS receptor.

Reference

Agertoft L, Pedersen S. A randomized, double-blind dose reduction study to compare the minimal effective dose of budesonide Turbuhaler and fluticasone propionate Diskhaler. J Allergy Clin Immunol 1997;99:773-80.

For each of the new HFA pMDI formulations, the effects will be specific to the product and the inhaler and generalised comparisons should not be made. Any claims of potency differences between different inhalers must be based on proper dose-response studies as outlined above.

Read more about the relation between Turbuhaler^® and Diskus™.