New data show Symbicort used as an anti-inflammatory reliever in mild-to-moderate asthma is more effective at preventing severe asthma attacks than maintenance budesonide plus terbutaline taken as-needed

Second trial reflecting real-world practice shows the benefit of anti-inflammatory reliever therapy at reducing the risk of severe asthma exacerbations

Results published in The Lancet
 

New data from PRACTICAL, an independent trial, has demonstrated that Symbicort Turbuhaler (budesonide/formoterol) used as an anti-inflammatory reliever in mild-to-moderate asthma reduced the rate of severe exacerbations versus maintenance budesonide plus terbutaline taken as-needed, a comparator regimen representative of usual care.^1,2 These results are published in The Lancet.¹

The open-label PRACTICAL trial compared Symbicort Turbuhaler, which contains budesonide, an inhaled corticosteroid (ICS), and formoterol, a long-acting beta2-agonist, taken only as-needed versus budesonide taken twice daily, an ICS maintenance treatment, plus terbutaline, a short-acting beta2-agonist (SABA) reliever, taken as-needed.¹

Symbicort Turbuhaler taken as an anti-inflammatory reliever was more effective at reducing the rate of severe exacerbations (absolute rate 0·119 versus 0·172 per patient per year; relative rate, 0·69; 95% confidence interval 0.48-1.00; p=0·049) and had a longer time to first severe exacerbation (p=0.015) versus maintenance budesonide plus terbutaline taken as-needed.¹ This 31% reduction in severe exacerbation risk with Symbicort Turbuhaler was achieved with no statistically significant difference in asthma symptom control as measured by the Asthma Control Questionnaire (ACQ) or lung function as measured by FEV1.¹

Lead author and one of the investigators of the trial, Dr Jo Hardy of the Medical Research Institute of New Zealand said: “There is a substantive burden from severe asthma attacks in patients with mild-to-moderate asthma. These new data from the PRACTICAL trial demonstrate that Symbicort Turbuhaler used as-needed is superior to regular inhaled steroid therapy plus a reliever inhaler at reducing the rate of severe attacks in patients with mild-to-moderate asthma. These results build on previous findings with anti-inflammatory reliever therapy from the SYGMA and Novel START trials.”

Alex de Giorgio-Miller, Therapy Area Vice President, Respiratory, Global Medical Affairs, said: “Up to 30% of patients with mild-to-moderate asthma experience severe attacks each year. It is therefore of particular clinical interest that patients in PRACTICAL had significantly fewer severe attacks, with no statistically significant difference in either symptom control or lung function, compared to those receiving regular inhaled corticosteroid therapy. These data add to the body of evidence demonstrating the potential of Symbicort Turbuhaler as an important treatment option for patients with mild-to-moderate disease at risk of asthma attacks where licensed.”

PRACTICAL is a peer-reviewed trial that was independently funded by the Health Research Council of New Zealand.

Safety and tolerability data for Symbicort Turbuhaler as-needed were consistent with the known profile of the medicine. The most commonly reported adverse events in the PRACTICAL trial were nasopharyngitis, asthma, upper and lower respiratory tract infection, and influenza.¹

About the PRACTICAL trial

The primary objective of the PRACTICAL (PeRsonalised Asthma Combination Therapy with an Inhaled Corticosteroid And fast-onset Long acting beta agonist) trial was to compare the efficacy of Symbicort Turbuhaler given as-needed with maintenance ICS and SABA reliever therapy in adults with mild-to-moderate asthma.¹

This 52-week, open-label, parallel-group, multicentre, randomised controlled trial reflecting real-world practice recruited 890 patients (five patients were ineligible and subsequently withdrawn from the analysis) with a self-reported doctor-diagnosis of asthma, aged 18 to 75 years, from 15 clinical trial sites in New Zealand.¹

Patients with mild-to-moderate asthma were enrolled if they were using SABA for symptom relief, with or without maintenance low- or moderate-dose ICS. At baseline 264/885 (30%) were taking SABA reliever therapy alone and 621/885 (70%) were taking an ICS.¹

In the trial, Symbicort Turbuhaler as-needed 200/6mcg (n=437) was compared to maintenance ICS therapy with budesonide Turbuhaler 200mcg twice-daily plus terbutaline Turbuhaler 500mcg as-needed (n=448).¹

The comparator reflects one of the treatment options most commonly used in clinical practice for the management of mild-to-moderate asthma.¹ The primary outcome was the rate of severe exacerbations, defined as the use of at least three days of systemic corticosteroids for asthma in the community or hospital/emergency department visit because of asthma requiring systemic corticosteroids.¹

Full results of the primary and key secondary outcome measurements are:

• Symbicort Turbuhaler reliever therapy resulted in a lower rate of severe exacerbations (absolute rate 0·119 vs. 0·172 per patient per year; relative rate, 0·69, 95% CI 0·48-1·00; p=0·049) and had a longer time to first severe exacerbation (p=0.015) compared with maintenance budesonide plus terbutaline taken as-needed.¹
• This 31% reduction in severe exacerbation risk was achieved despite patients in the Symbicort Turbuhaler reliever group using about 60% of the dose of budesonide (based on electronic monitoring of inhaler use in a sub-group of 110 patients).¹
• There was no statistically significant difference in asthma symptom control or lung function, as measured by Asthma Control Questionnaire (ACQ-5) and FEV1 respectively, between the treatment groups¹
  • Across all timepoints, ACQ-5 score with Symbicort Turbuhaler reliever therapy did not differ from maintenance budesonide plus terbutaline taken as-needed (mean difference 0·06, 95% CI –0·005 to 0·12; p=0.07).
  • Additionally, across all timepoints, FEV1 with Symbicort Turbuhaler reliever therapy did not differ from maintenance budesonide plus terbutaline taken as-needed (mean difference 0·006 L; 95% CI –0·026 to 0·04; p=0·69).
• The findings from sub-group analyses, including baseline ICS use, frequency of reliever use, and biomarkers of airway inflammation were consistent with the treatment effect being similar in all patient sub-groups, suggesting that the findings are generalisable across the spectrum of mild and moderate asthma.¹

PRACTICAL is a fully independent, investigator-led clinical trial. AstraZeneca did not provide funding or input into trial design or execution.

About the Novel START and SYGMA trials

Novel START (Novel Symbicort Turbuhaler Asthma Reliever Therapy) is Externally Sponsored Scientific Research (ESR). The primary objective of the trial was to assess the efficacy of Symbicort Turbuhaler given as an anti-inflammatory reliever as-needed in adults with mild asthma.³ Results from the study were published in The New England Journal of Medicine.³

The SYGMA trial programme comprised SYGMA 1 and 2: two 52-week Phase III trials in more than 8,000 patients.⁴ SYGMA 1 evaluated Symbicort Turbuhaler (200/6mcg) ‘as needed’, compared with terbutaline (0.5mg) ‘as needed’ and budesonide (200mcg) twice-daily plus terbutaline (0.5mg) ‘as needed’.⁵ Results from SYGMA 1 were published in The New England Journal of Medicine.⁵ SYGMA 2 evaluated Symbicort Turbuhaler (200/6mcg) ‘as needed’, compared with budesonide (200mcg) twice-daily maintenance plus terbutaline (0.5mg) ‘as needed’.⁶ Results were published in The New England Journal of Medicine.⁶

About asthma 

Asthma is a common chronic respiratory disease, and it affects the health and day-to-day lives of as many as 339 million adults and children worldwide.⁷ It is characterised by recurrent breathlessness and wheezing which varies over time, and which varies in severity and frequency from person to person.⁸

All asthma patients are at risk of severe exacerbations regardless of their disease severity, adherence to treatment or level of control.^9,10,11 There are an estimated 176 million asthma exacerbations globally per year;¹² these are physically threatening and emotionally significant for many patients.¹³ However, despite the fact that asthma is a chronic, variable inflammatory disease, patients are either under-prescribed or under-use their anti-inflammatory ‘preventer’ therapy and over-rely on their SABA reliever, which can mask symptom worsening.^14,15,16,17 Taking a SABA inhaler alone during or after a worsening of symptoms does not address the underlying inflammation, leaving patients at risk of asthma exacerbations and potential exposure to frequent bursts of oral corticosteroids.¹⁸

About Symbicort

Symbicort is a combination formulation containing budesonide, an inhaled corticosteroid (ICS) that treats underlying inflammation, and formoterol, a long-acting beta2-agonist bronchodilator (LABA) with a fast onset of action, in a single inhaler. Symbicort is approved as a treatment regimen for patients with moderate to severe disease and for patients with all severities in Brazil, Russia, Australia and New Zealand. Symbicort was launched in 2000 and is approved in approximately 120 countries to treat asthma and/or COPD either as Symbicort Turbuhaler or Symbicort pMDI (pressurised metered-dose inhaler). 

About AstraZeneca in respiratory diseases 

Respiratory is one of AstraZeneca’s main therapy areas, and our medicines reached more than 18 million patients as maintenance therapy in 2018. AstraZeneca’s aim is to transform asthma and COPD treatment through inhaled combinations at the core of care, biologics for the unmet needs of specific patient populations, and scientific advancements in disease modification.

The Company is building on a 40-year heritage in respiratory disease and AstraZeneca’s capability in inhalation technology spans pressurised metered-dose inhalers and dry powder inhalers, as well as the Aerosphere delivery technology. The company also has a growing portfolio of respiratory biologics including Fasenra (anti-eosinophil, anti‒IL-5Rɑ), now approved for severe, eosinophilic asthma and in development for severe nasal polyposis and other potential indications, and tezepelumab (anti-TSLP), which has been granted Breakthrough Therapy Designation by the US Food and Drug Administration in patients with severe asthma and is in Phase III trials. AstraZeneca’s research aims at addressing underlying disease drivers by focusing on the lung epithelium, lung immunity, lung regeneration and neuronal functions. 

About AstraZeneca

AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of diseases in three therapy areas - Oncology, CVRM and Respiratory. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information, please visit astrazeneca.com and follow us on Twitter @AstraZeneca.

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References

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^{2.       Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2019. Available from: www.ginasthma.org [Last accessed 22 August 2019]}

^{3.       Beasley RW, Holliday M, Reddel HK, et al. Controlled trial of budesonide-formoterol as needed for mild asthma. N Engl J Med. 2019; 380: 2020-2030}

^{4.       O’Byrne PM, FitzGerald JM, Zhong N, et al. The SYGMA programme of phase 3 trials to evaluate the efficacy and safety of budesonide/formoterol given “as needed” in mild asthma: study protocols for two randomised controlled trials. Trials. 2017; 18: 12.}

^{5.       O’Byrne PM, FitzGerald JM, Bateman ED, et al. Inhaled combined budesonide-formoterol as needed in mild asthma. N Engl J Med. 2018; 378: 1865-1876.}

^{6.       Bateman ED, Reddel HK, O’Byrne PM, et al. As-needed budesonide-formoterol versus maintenance budesonide in mild asthma. N Engl J Med. 2018; 378: 1877-1887.}

^{7.       The Global Asthma Network. The Global Asthma Report 2019. [Online]. Available at: globalasthmanetwork.org/publications/Global_Asthma_Report_2019.pdf Accessed August 2019.} 

^{8.       From: Section 2, Definition, Pathophysiology and Pathogenesis of Asthma, and Natural History of Asthma. Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma. National Asthma Education and Prevention Program, Third Expert Panel on the Diagnosis and Management of Asthma. Bethesda (MD): National Heart, Lung, and Blood Institute (US). 2007.} 

^{9.       Olaguibel JM, Quirce S, Julia B, et al. Measurement of asthma control according to Global Initiative for Asthma guidelines: a comparison with the Asthma Control Questionnaire. Respir Res. 201; 13: 50.} 

^{10.    Price D, Fletcher M, van der Molen T. Asthma control and management in 8,000 European patients: the REcognise Asthma and LInk to Symptoms and Experience (REALISE) survey. NPJ Prim Care Respir Med. 2014; 24: 14009.} 

^{11.    Bateman ED, Hurd SS, Barnes PJ, et al. Global strategy for asthma management and prevention: GINA executive summary. Eur Respir J. 2008; 31: 143–78.} 

^{12.    AstraZeneca Pharmaceuticals. Data on file. Budesonide/formoterol: Annual Rate of Exacerbations Globally (ID:SD-3010-ALL-0017).} 

^{13.    Sastre J, Fabbri LM, Price D, et al. Insights, attitudes, and perceptions about asthma and its treatment: a multinational survey of patients from Europe and Canada. World Allergy Organ J. 2016; 9: 13.} 

^{14.    Humbert M, Andersson TL, Buhl R. Budesonide/formoterol for maintenance and reliever therapy in the management of moderate to severe asthma. Allergy. 2008; 63: 1567–80.} 

^{15.    Rabe KF, Vermeire PA, Soriano JB, Maier WC. Clinical management of asthma in 1999: the asthma insights and reality in Europe (AIRE) study. Eur Respir J. 2000; 16: 802–7.} 

^{16.    Tattersfield AE, Postma DS, Barnes PJ, et al. on behalf of the FACET International Study Group. Exacerbations of asthma: a descriptive study of 425 severe exacerbations. Am J Respir Crit Care Med. 1999; 160: 594–9.} 

^{17.    Adams RJ, Fuhlbrigge A, Guilbert T, et al. Inadequate use of asthma medication in the United States: results of the asthma in America national population survey. J Allergy Clin Immunol. 2002; 110: 58–64.} 

^{18.      Price DB, Trudo F, Voorham J, et al. Adverse outcomes from initiation of systemic corticosteroids for asthma: long-term observational study. J Asthma Allergy. 2018; 11: 193–204.}