TORCH study
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  • NICE have suggested that inhaled steroids should be used in a combination inhaler as an option if FEV1 <50% in people with stable COPD who remain breathless or have exacerbations despite using short-acting bronchodilators as required (1)

    • offer once-daily long-acting muscarinic antagonist (LAMA) in preference to four-times-daily short-acting muscarinic antagonist (SAMA) to people with stable COPD who remain breathless or have exacerbations despite using short-acting bronchodilators as required, and in whom a decision has been made to commence regular maintenance bronchodilator therapy with a muscarinic antagonist
    • in people with stable COPD who remain breathless or have exacerbations despite using short-acting bronchodilators as required, offer the following as maintenance therapy:
      • if FEV1 >= 50% predicted: either long-acting beta2 agonist (LABA) or LAMA
      • if FEV1 < 50% predicted: either LABA with an inhaled corticosteroid (ICS) in a combination inhaler, or LAMA
    • in people with stable COPD and an FEV1 >=50% who remain breathless or have exacerbations despite maintenance therapy with a LABA:
      • consider LABA+ICS in a combination inhaler
      • consider LAMA in addition to LABA where ICS is declined or not tolerated
    • offer LAMA in addition to LABA+ICS to people with COPD who remain breathless or have exacerbations despite taking LABA+ICS, irrespective of their FEV1
    • consider LABA+ICS in a combination inhaler in addition to LAMA for people with stable COPD who remain breathless or have exacerbations despite maintenance therapy with LAMA irrespective of their FEV1

  • ICSs are unlikely to have any clinically significant effect on the decline in FEV1 in COPD patients in the long-term (2)
    • NICE suggest the use of ICSs in COPD in patients with an FEV1<50% of predicted as a treatment measure to reduce exacerbation rates and slow the decline in health status (i.e. improve quality of life) and, not specifically, improve lung function
      • an example of a study of ICS in COPD is the Inhaled Steroids in Chronic Lung Disease in Europe (ISCLDE) included 990 patients with moderate to severe COPD. The patients were randomised to fluticasone dipropionate (500 mcg bd) or placebo bd for 3 years. It showed that:
        • treatment with inhaled fluticasone propionate reduced the absolute decline in lung function by 32% over 3 years, compared with placebo.
        • treatment with fluticasone propionate reduced the absolute decline in FEV1 by 32% over 3 years.
        • treatment with fluticasone propionate reduced exacerbation rate by 25%.
  • there is insufficient evidence to establish the minimum dose of ICS required to be of benefit
    • there is also limited experience of doses higher than 1000mcg fluticasone/day (or equivalent) and no evidence that any one ICS is superior to any other
  • inhaled salmeterol plus fluticasone (50/500mcg) (3,4):
    • the use of combination treatment of inhaled salmeterol plus fluticasone has been investigated in the TORCH study
      • TORCH study (TOwards a Revolution in Chronic obstructive pulmonary disease [COPD] Health)
        • randomised double-blind study in 6,112 patients with COPD
          • compared the effects of inhaled salmeterol plus fluticasone (50/500mcg) with placebo, salmeterol (50mcg) alone or fluticasone (500mcg) alone
        • primary outcome was death from any cause for the comparison between the combination regimen and placebo
          • after three years, the proportion of deaths in the combination treatment group was not statistically significantly lower than in the placebo group (12.6% vs. 15.2%, respectively; hazard ratio 0.83, 95%CI 0.68 to 1.00, P=0.052)
          • combination therapy did significantly reduce the annual rate of exacerbations but, importantly, not the rate of severe exacerbations requiring hospitalisation, compared with salmeterol
          • pneumonia occurred more frequently in the combination and fluticasone groups, than in the salmeterol and placebo groups (19% vs. 13%) - means that, for every 17 people treated for three years with an inhaler containing fluticasone, instead of salmeterol alone or placebo, one suffered pneumonia
    • a systematic review comparing corticosteroids plus long-acting beta-agonists versus steroids alone in patients with COPD concluded (5):
      • combination therapy was more effective than long-acting beta-agonists in reducing exacerbation rates, although the evidence for the effects on hospitalisations was mixed, and requires further exploration
        • no significant impact on mortality was found even with additional information from the TORCH trial
      • authors noted that the superiority of combination inhalers should be viewed against the increased risk of side-effects, particularly pneumonia
  • inhaled steroids in COPD and risk of pneumonia and osteoporosis
    • ICSs (alone and in combination with LABAs) increase the risk of pneumonia in patients with COPD (6). The potential risk of developing osteoporosis and other side effects in patients treated with high-dose ICSs should also be considered (6)
      • the INSPIRE study, a head-to-head comparison of salmeterol/fluticasone with tiotropium found the risk of pneumonia was almost doubled in the combination group (8% vs. 4%; HR for time to pneumonia 1.94, 95%CI 1.19 to 3.17, P=0.008)
      • this evidence is supported by TORCH study where pneumonia occurred more frequently in the combination and fluticasone groups, than in the salmeterol and placebo groups (19% vs. 13%)
      • meta-analysis studies have also identified an increased risk of pneumonia associated with inhaled corticosteroid use in COPD (8,9)
      • a more recent meta-analysis revealed that nhaled corticosteroids, when added to long-acting beta-agonists, reduce exacerbations of COPD only in patients with COPD with FEV1 <= 40% (10)
    • clinicians should be aware of the potential risk of osteoporosis and other side effects in patients using a high-dose ICS (especially if they have other risk factors e.g. postmenopausal). It is important that these risks should be discussed with patients
    • clinicians must be aware of the potential risk of developing side effects (including non-fatal pneumonia) in people with COPD treated with inhaled corticosteroids and be prepared to discuss with patients (1)

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