combination therapy long acting inhaled beta agonists and inhaled steroids in asthma

Last reviewed 01/2018

• a sytematic review investigated the use of inhaled steroids alone versus a combinination of inhaled steroid + inhaled long-acting beta-2 agonist in steroid naive patients
  • the review concluded that (1):
    • in steroid-naive patients with mild to moderate airway obstruction, the initiation of inhaled corticosteroids in combination with long-acting beta2-agonists does not significantly reduce the rate of exacerbations over that achieved with inhaled corticosteroids alone; it does improve lung function and symptom-free days but does not reduce rescue beta2-agonist use as compared to inhaled steroids alone. Both options appear safe. There is insufficient evidence at present to recommend use of combination therapy rather than ICS alone as a first-line treatment
  • a further systematic review found that evidence does not support the use of combination therapy with an inhaled corticosteroid plus a long-acting beta2 agonist as first choice preventer therapy in adults and children with persistent asthma, without a prior trial of inhaled corticosteroid alone (2)
  • a Cochrane review found no significant difference in serious adverse events when different combinations of inhaled corticosteroids and long-acting beta2 agonists were compared in people with chronic asthma. However, as these events were rare, there was insufficient evidence to know for certain whether regular formoterol and budesonide (or formoterol and beclometasone) has an equivalent, or different, safety profile from salmeterol and fluticasone. There were little comparative safety data on formoterol and beclometasone, and no data available in children (3)
• inhaled corticosteroid vesus combination of inhaled steroid plus long-acting inhaled beta2 agonist in patients with inadequately controlled asthma
  • in asthmatic patients inadequately controlled on inhaled corticosteroids and/or those with moderate persistent asthma, two main options are recommended: the combination of a long-acting inhaled beta2 agonist (LABA) with inhaled corticosteroids (ICS) or use of a higher dose of inhaled corticosteroids
    • a systematic review was undertaken to determine, in asthmatic patients, the effect of the combination of long-acting beta2 agonists and inhaled corticosteroids compared to a higher dose of inhaled corticosteroids on the incidence of asthma exacerbations, on pulmonary function and on other measures of asthma control and to look for characteristics associated with greater benefit for either treatment option
    • the systematic review concluded (4)
      • in adult asthmatics, there was no significant difference between the combination of LABA and ICS and a higher dose of ICS for the prevention of exacerbations requiring systemic corticosteroids. Overall, the combination therapy led to greater improvement in lung function, symptoms and use of rescue beta2 agonists, (although most of the results are from trials of up to 24 weeks duration). There were less withdrawals due to poor asthma control in this group than when using a higher dose of inhaled corticosteroids. Apart from an increased rate of tremor, the two options appear safe although adverse effects associated with long-term ICS treatment were seldom monitored
• risk of asthma-relaed hospitalisations if inhaled corticosteroid therapy plus long-acting inhaled beta2 agonist
  • in patients with asthma using inhaled corticosteroid therapy, long-acting beta agonist inhaled therapy did not increase the risk of asthma-related hospitalizations (5)

Reference:

• (1) Ni CM et al. Addition of inhaled long-acting beta2-agonists to inhaled steroids as first line therapy for persistent asthma in steroid-naive adults. Cochrane Database Syst Rev. 2005 Apr 18;(2):CD005307
• (2) Ni Chroinin M, Greenstone I, Lasserson TJ, et al. Addition of inhaled long-acting beta2-agonists to inhaled steroids as first line therapy for persistent asthma in steroid-naïve adults and children. Cochrane Database of Systematic Reviews 2009, Issue 4. Art. No.: CD005307. DOI:10.1002/14651858.CD005307.pub2
• (3) Cates CJ, Lasserson TJ. Regular treatment with formoterol and an inhaled corticosteroid versus regular treatment with salmeterol and an inhaled corticosteroid for chronic asthma: serious adverse events. Cochrane Database of Systematic Reviews 2010, Issue 1. Art. No.: CD007694. DOI: 10.1002/14651858.CD007694.pub2
• (4) Greenstone IR et al. Combination of inhaled long-acting beta2-agonists and inhaled steroids versus higher dose of inhaled steroids in children and adults with persistent asthma. Cochrane Database Syst Rev. 2005 Oct 19;(4):CD005533
• (5) Jaeschke R et al.The safety of long-acting beta-agonists among patients with asthma using inhaled corticosteroids: systematic review and metaanalysis. Am J Respir Crit Care Med. 2008 Nov 15;178(10):1009-16.