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Achieving asthma control with ICS/LABA: A review of strategies for asthma management and prevention

Achieving asthma control with ICS/LABA: A review of strategies for asthma management and prevention

R. Aalbers, C. Vogelmeier, P. Respir Med 2016

Introduction:
  • GOAL and FACET were two landmarks studies which demonstrated the advantages of adding a LABA to an ICS by comparing salmeterol/fluticasone or budesonide/formoterol with ICS alone.
  • The aim of this publication was to review the role of ICS/LABA considering both current control and future risk with a focus on the maintenance and reliever approach.
  • It also explains how data from the budesonide/formoterol and beclometasone/formoterol maintenance and reliever therapy studies, in particular, expand upon the findings of both GOAL and FACET.
Achieving current control and reducing future risk: the GOAL and FACET studies findings
  • The FACET study2 demonstrated that addition of formoterol to budesonide enhanced current control compared with an increased dose of budesonide. Indeed, the number of episode-free days was significantly increased with the addition of formoterol 12 µg to twice-daily budesonide 100 µg but there was no significant increase with twice-daily budesonide 400 µg alone.
  • The GOAL study3 demonstrated that the addition of salmeterol to fluticasone improved health status and significantly reduced the exacerbation rate compared with fluticasone alone. However, the study was not designed to determine whether the addition of salmeterol to fluticasone was more beneficial than increasing the dose of fluticasone alone.
  • Interestingly, in the GOAL study, many of the patients achieved total asthma control at the lowest dose of ICS. The results of this study therefore bring into question the benefits of increasing the maintenance dose of ICS until total control is achieved.
Beyond FACET and GOAL: The ICS/LABA maintenance and reliever approach
 
  •  By employing the ICS/LABA maintenance and reliever strategy, patients receive ICS in addition to a fast-acting bronchodilator whenever they require reliever medication, meaning that inflammation can be targeted when symptoms increase.
  • In particular, the STAY4, COMPASS5 and AHEAD6 studies built on GOAL and FACET by comparing budesonide/formoterol maintenance and reliever therapy with two different doses of budesonide/formoterol plus SABA, budesonide plus SABA and salmeterol/fluticasone plus SABA.
  • In COMPASS and AHEAD, severe exacerbations occurred less frequently among patients treated with budesonide/formoterol for maintenance and relief compared with salmeterol/fluticasone plus SABA (-39%(p<0.001) and -21% (p=0.039) respectively).

    These results were also obtained at a lower ICS dose in the budesonide/formoterol for maintenance and relief group compared with salmeterol/fluticasone plus SABA (-25% and -38% (p<0.001) respectively).
  •  The use of beclometasone/formoterol maintenance and reliever therapy has only been investigated in one study. In this study, the time to first exacerbation was significantly increased with beclometasone/ formoterol maintenance and reliever therapy compared with beclometasone/formoterol plus as-needed salbutamol.
  • In addition to the studies discussed above, the use of budesonide/formoterol as maintenance and reliever therapy has been assessed in over 23,000 patients as part of four real-world studies that included comparisons with salmeterol/fluticasone (COSMOS 7) or conventional best practice (SALTO 8) and an evaluation of a range of doses. Budesonide/formoterol maintenance and reliever therapy was shown to improve asthma control and reduce the frequency of exacerbations compared with either salmeterol/fluticasone or conventional best practice.Patients treated with budesonide/formoterol for maintenance and relief received a reduced overall mean daily dose of ICS compared with conventional best practice.
ICS/LABA maintenance and reliever approach: airway inflammation and remodelling
  • As the use of ICS/LABA for both maintenance and relief may lead to a reduction in the dose of ICS required to maintain stable disease, concerns have previously been raised that this approach may reduce the frequency of exacerbations without controlling airway inflammation and remodelling.
  • In a 12-month parallel group, randomised study, budesonide/formoterol maintenance and reliever therapy reduced airway remodelling as effectively as the high dose of budesonide/formoterol plus SABA, as indicated by the lack of between-group differences in reduction of reticular basement membrane thickness over 12 months.
Conclusion

While one clinical study has demonstrated that beclometasone/formoterol maintenance and reliever therapy is more effective at reducing asthma exacerbations than beclometasone/formoterol plus SABA, there is a large body of evidence to show that treatment with budesonide/formoterol maintenance and reliever therapy improves both current control and future risk compared with ICS/LABA plus SABA.


References:
1. Aalbers et al., Respir Med. 2016; 111:1-7.

2. Pauwels et al. N Eng J Med 1997; 337:1405-1411

3. Bateman et al. Am. J. Respir. Crit. Care Med. 2004; 170: 836-8443

4. O’Byrne PM, et al. Am J Respir Crit Care Med 2005;171:129–136

5. Kuna P et al. Int. J. Clin. Pract. 2007; 61:725-36

6. Bousquet J et al. Respir Med 2007;101:2437-2446

7. Vogelmeier C et al. Eur Respir J 2005; 26: 819-828

8. Louis R et al. Int J Clin Pract. 2009 Oct;63(10):1479-88

NS ID XL-0210-RD12/2017-WEB