3 The technologies
3.1 ICSs suppress inflammation in the lungs and are recommended for prophylactic treatment of asthma. Five corticosteroids are available as inhaled formulations for the treatment of asthma: beclometasone dipropionate, budesonide, fluticasone propionate, mometasone furoate and ciclesonide. Two of the ICSs are available in combination with a LABA in a single inhaler (fluticasone propionate in combination with salmeterol and budesonide in combination with formoterol fumarate). The budesonide/formoterol fumarate combination device may be used as part of a flexible dosing regimen; as adjustable maintenance dosing and as maintenance and reliever therapy in people aged 18 years and over. For further details of available products that are included in this appraisal please see appendix C.
3.2 The BTS/SIGN guidelines advise on equivalent doses of the different ICSs. Budesonide and beclometasone dipropionate are considered equivalent on a microgram for microgram basis (1:1 dose ratio). Half the dose of fluticasone propionate, mometasone furoate or ciclesonide in micrograms is equivalent to a given dose of budesonide/beclometasone dipropionate (2:1 dose ratio). One type of hydrofluoroalkane (HFA)-propelled beclometasone dipropionate pressurised metered-dose inhaler (pMDI) (Qvar, IVAX) device delivers beclometasone dipropionate in extra fine particles so that more is deposited in the lungs, leading to a 2:1 dose ratio with the CFC budesonide/beclometasone dipropionate devices.
3.3 ICSs are available in a variety of devices. These are broadly of two types pMDIs, in which the drug is suspended in either a CFC or HFA propellant, and dry powder inhalers (DPIs), in which there is no liquid propellant. It is expected that those using CFC propellants will soon be phased out in line with the Montreal Protocol. Many people have difficulty coordinating device actuation and inhalation with pMDIs. This can be overcome to some extent by using a spacer device to improve airway deposition and reduce oropharyngeal deposition, or by using 'breath-actuated' pMDI devices. DPIs deliver micronised drug, sometimes with a carrier powder, and use the individual's own inspiratory flow to disperse the fine powder. Breath-actuated pMDIs and DPIs can be used to overcome the problem of actuation–inhalation coordination associated with pMDIs but DPIs and, in general, breath-actuated pMDIs cannot be used in conjunction with spacer devices.
3.4 Beclometasone dipropionate, budesonide and fluticasone propionate are available as pMDIs and DPIs. Ciclesonide is only available as a pMDI and mometasone furoate is only available as a DPI. The fluticasone propionate/salmeterol combination device is available both as a pMDI and as a DPI, and the budesonide/formoterol fumarate combination device is currently available as a DPI only. For further details of available products that are included in this appraisal please see appendix C.
3.5 The side effects of ICSs may be local (following deposition in the upper airways) or systemic (following absorption into the bloodstream). Local adverse effects include dysphonia, oropharyngeal candidiasis, cough, throat irritation and reflex bronchospasm. Local adverse effects can be minimised by optimising inhaler technique and using a spacer with the inhaler device. Systemic adverse effects include suppression of the hypothalamic-pituitary-adrenal axis, osteoporosis, skin thinning and easy bruising, cataract formation and glaucoma, and growth retardation in children and adolescents. Systemic adverse effects tend to be associated with higher doses of corticosteroids and can differ depending on both the drug and the delivery system. For full details of side effects and contraindications, see the summaries of product characteristics.
3.6 Each ICS is available in a variety of devices and strengths. In general, the DPIs are the most expensive and the CFC-containing products are the cheapest. Breath-actuated aerosol MDIs are generally more expensive than those that are not breath actuated. The CFC-free devices that contain a HFA propellant are more expensive than CFC-containing ones. Costs may vary in different settings because of negotiated procurement discounts.