Extensive new data further confirms efficacy of budesonide/formoterol maintenance and reliever therapy in reducing exacerbations

Main Category: Respiratory / Asthma
Also Included In: Pharma Industry / Biotech Industry
Article Date: 20 Sep 2007 - 14:00 PDT

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New data presented at the European Respiratory Society (ERS) congress demonstrate the efficacy of budesonide/formoterol maintenance and reliever therapy (Symbicort SMART*) in reducing exacerbations and improving daily asthma control in patients with uncontrolled asthma. This further illustrates the additional benefits of this new asthma management approach (one inhaler for both maintenance and for relief) over traditional treatment regimens; salmeterol/fluticasone and budesonide/formoterol plus separate reliever medication in achieving reductions in exacerbations.

This data, from further analyses of the COMPASS study, show that budesonide/formoterol used as both maintenance and reliever therapy is more effective in reducing exacerbations in patients with average or above average need for reliever medication than fixed doses of salmeterol/fluticasone or budesonide/formoterol plus separate reliever medication.1 A further post hoc analysis of this patient population from COMPASS2 demonstrates that in patients symptomatic on high doses of inhaled corticosteroids, budesonide/formoterol used as both maintenance and reliever therapy reduced the rate of exacerbations by 57 percent when compared to higher, fixed maintenance doses of salmeterol/fluticasone ( p≤0.03) plus separate reliever medication, and 42 percent compared to higher fixed maintenance doses of budesonide/formoterol plus separate reliever medication.

"These data show that budesonide/formoterol maintenance and reliever therapy is more effective in reducing exacerbations even in patients with poorly controlled asthma - demonstrated by the presence of asthma symptoms or increased need for reliever therapy - than traditional approaches such as increased doses of ICS/LABA," commented Piotr Kuna, President of the Polish Society of Allergology and one of the authors of the COMPASS study. "This new approach enables patients to treat the underlying cause of asthma each time they use their inhaler which may help patients to achieve better day-to-day control of their asthma."

Budesonide/formoterol maintenance and reliever therapy is the first treatment approach to provide patients with both asthma maintenance and reliever therapy together in one inhaler; budesonide (an anti-inflammatory therapy that acts within hours) and formoterol (a bronchodilator that is both rapid in effect and long lasting). With budesonide/formoterol maintenance and reliever therapy, patients treat the underlying inflammation of their airways with every inhalation, whether used for maintenance or symptom relief. This treatment approach is given an Evidence A rating in the recently updated (November 2006) Global Initiative for Asthma's (GINA) Global Strategy for Asthma Management and Prevention.3

Data from the AHEAD study,4 also presented at ERS, demonstrate that budesonide/formoterol used as both maintenance and reliever therapy had a numerically lower risk of a first exacerbation (p=0.12) and was more effective in reducing the incidence of asthma exacerbations by 21 percent (p=0.039) compared to the highest approved dose of salmeterol/fluticasone plus separate reliever medication. In addition, the rate of hospitalisations/emergency room visits decreased by 31 percent (p=0.046) using budesonide/formoterol maintenance and reliever therapy.4 Similar improvements in daily asthma control were seen between groups, with lower use of inhaled corticosteroids (ICS) in the budesonide/formoterol maintenance and reliever therapy group. Data from a clinical safety data review, also presented at ERS, further add to the evidence supporting the use of formoterol as a long-acting beta-agonist (LABA) in asthma treatment.5

An analysis of the AHEAD study also showed that budesonide/formoterol maintenance and reliever therapy provides a more cost-effective management approach to asthma treatment than high-dose salmeterol/fluticasone, lowering the direct healthcare costs by €2330 per 100 patients.6

"Updated guidelines issued by the Global Initiative for Asthma focus strongly on the importance of achieving satisfactory control of asthma symptoms, such as exacerbations. The data presented at ERS add to a strong bank of clinical evidence to support the use of budesonide/formoterol maintenance and reliever therapy and suggest that this new management approach could help physicians and patients to meet the recommendations of GINA," concluded Jean Bousquet, Professor of Respiratory Medicine, Montpellier University, Editor of Allergy and Chairman of the Global Alliance against Chronic Respiratory Diseases (GARD).

AstraZeneca is a major international healthcare business engaged in the research, development, manufacture and marketing of prescription pharmaceuticals and the supply of healthcare services. It is one of the world's leading pharmaceutical companies with healthcare sales of $26.47 billion and leading positions in sales of gastrointestinal, cardiovascular, neuroscience, respiratory, oncology and infection products. AstraZeneca is listed in the Dow Jones Sustainability Index (Global) as well as the FTSE4 Good Index.

References

1. Buhl R, Kuna P on behalf of the COMPASS investigators; Does the choice of ICS/LABA regimen influence exacerbation rates in asthma patients with high as-needed use? Abstract presented at ERS 2007

2. Kuna P, Peters M, Buhl R for the COMPASS study investigators; Budesonide/formoterol for maintenance and relief vs. higher dose ICS/LABA therapy: Outcomes in patients symptomatic on high-dose inhaled corticosteroids (HDICS). Abstract presented at ERS 2007

3. Global Initiative for Asthma. Global strategy for asthma management and prevention 2006. Available from http://www.ginasthma.org Accessed July 13th 2007

4. Bousquet J and Boulet L-P for the AHEAD Investigators; Budesonide/formoterol as maintenance and reliever therapy in uncontrolled asthma compared with high dose salmeterol/fluticasone: The AHEAD double-blind study. Abstract presented at ERS 2007

5. Sears, M.R. et al; Safety of formoterol in asthma trials. Abstract presented at ERS 2007

6. Bousquet J, Miravitlles M and Wiren A; Budesonide/formoterol provides better efficacy at a lower or similar cost as compared to high-dose salmeterol/fluticasone treatment. Abstract presented at ERS 2007

* Symbicort SMART is a trade mark of the AstraZeneca group of companies

COMPASS - high as-needed use1

- Using the data from the COMPASS study1, the efficacy of budesonide/formoterol maintenance and reliever therapy was compared with fixed doses of budesonide/formoterol and salmeterol/fluticasone plus separate reliever therapy in patients with varying levels of rescue use

Results showed that:

- Budesonide/formoterol maintenance and reliever therapy is more effective in patients with average or above average need for reliever therapy

- Salmeterol/fluticasone use was associated with an increased need for emergency treatment compared to both budesonide/formoterol regimens

COMPASS - pre-study high ICS2

- An analysis of the subgroup of patients (n=525) from the COMPASS study1 using high-dose inhaled corticosteroids (HDICS) at study entry

- The subanalysis was conducted to asses the efficacy of budesonide/formoterol maintenance and reliever therapy in symptomatic patients on HDICS compared to higher fixed-doses of budesonide/formoterol 320/9 mcg bid and salmeterol/fluticasone 250/50 plus separate reliever medication

Results showed that:

- Budesonide/formoterol maintenance and reliever therapy significantly reduced the rate of exacerbations by 42% and 57% compared to higher maintenance doses of budesonide/formoterol and salmeterol/fluticasone respectively plus reliever therapy

- Mean annualised exacerbation rates per 100 patients were 32, 55 and 75 with budesonide/formoterol maintenance and reliever therapy, budesonide/formoterol or salmeterol/fluticasone, respectively

- Similar trends in favour of budesonide/formoterol maintenance and reliever therapy were seen in hospitalisations/emergency room visits

- Patients treated with budesonide/formoterol maintenance and reliever therapy used ≈25% less ICS (beclomethasone equivalent) than patients in the fixed dose groups

The AHEAD Study4,6

- AHEAD was conducted to assess whether budesonide/formoterol used as both maintenance and reliever therapy is more effective in improving asthma control compared to sustained high-dose salmeterol/fluticasone 50/500 mcg bid plus separate reliever medication

Results showed that:

- The risk of having a first exacerbation is numerically lower for budesonide/mormoterol maintenance and reliever therapy but not significantly different between the groups (p=0.12).

- Budesonide/formoterol maintenance and reliever therapy is more effective in reducing the incidence of asthma exacerbations than sustained high-dose salmeterol/fluticasone (S/F) plus separate reliever medication

- Budesonide/formoterol maintenance and reliever therapy provides a more effective asthma treatment, at a lower or similar cost, than high-dose S/F

- Budesonide/formoterol maintenance and reliever therapy reduced exacerbation rates by 21% compared to S/F-treatment and reduced the rate of hospitalisations/ER visits by 31%

- Similar improvements in daily asthma control were seen between groups with lower use of inhaled corticosteroids in the budesonide/formoterol maintenance and reliever therapy group (BDP equivalents5 1238 ug/day vs. 2000 ug /day in the S/F plus reliever group, p<0.0001)

- Budesonide/formoterol maintenance and reliever therapy was associated with a reduction in health-care costs by €2330 and a reduction in total costs, including drug costs and costs for sick-leave by €5900, per 100 patients cf. Canadian, French and Spanish unit costs

LABA safety review5

- Following questions about safety of long-acting beta-agonist (LABA) therapy an analysis was conducted to investigate if formoterol use increased asthma mortality and non-fatal asthma related serious adverse events (SAEs)

- The analysis included 71,148 patients from 69 trials involving formoterol as maintenance, reliever or both, with inhaled corticosteroid (ICS) or as monotherapy

Results showed that:

- Use of formoterol in asthma patients mostly using ICS is not associated with increased asthma-related deaths or SAEs

- There were 8 asthma-related deaths among 50,549 formoterol-exposed patients (94% prescribed ICS) and 2 among 16,498 patients using other regimens, with no consistent patterns of timing, dose or duration of exposure

- Mortality in formoterol-exposed patients was not increased compared with patients not exposed to LABA

- Asthma-related SAEs were significantly reduced with formoterol exposure compared with non-LABA treatment and higher doses of formoterol were not associated with increased risk compared to lower doses

- Deaths and SAEs were slightly (non-significantly) higher among those using formoterol without ICS

Budesonide/Formoterol Maintenance and Reliever Therapy

- Patients prescribed budesonide/formoterol maintenance and reliever therapy take a maintenance dose of budesonide/formoterol every day in line with normal practice to establish asthma control and take additional inhalations 'as needed' of budesonide/formoterol if symptoms occur, to provide both rapid symptom relief and improved asthma control

- Budesonide/formoterol maintenance and reliever therapy successfully completed the European Union Mutual Recognition Procedure (MRP) in October 2006 and it is currently approved in over 60 countries worldwide (outside US).

GINA: Global strategy for asthma management and prevention 2006

Published November 2006 the Global strategy for asthma management and prevention is evidence-based guidelines for asthma management and prevention, with citations from the scientific literature. Evidence is from endpoints of well designed randomised controlled trials (RCTs) that provide a consistent pattern of findings in the population for which the recommendation is made. Category A, the highest category, requires substantial numbers of studies involving substantial numbers of participants to provide a rich body of data.

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