Real-world Effectiveness of Combination Therapy in Asthma
Real-world Effectiveness of Combination Therapy in Asthma
This study will evaluate and compare the effectiveness of asthma management in patients with
 evidence of persistent asthma following a switch in asthma therapy to combination inhaled
 glucocorticosteroid (ICS) / long-acting bronchodilator (LABA) therapy as either:
 fixed-combination fluticasone propionate / salmeterol (FP/SAL; Seretide®) via pressurised
 metered-dose inhaler (pMDI) or dry-powder inhaler (DPI) plus as-needed (prn) reliever therapy
 (salbutamol as DPI, BAI or pMDI), or fixed-combination budesonide / formoterol (BUD/FOR;
 Symbicort®) via DPI plus prn reliever therapy (salbutamol as DPI, BAI or pMDI or bricanyl as
 DPI). The final analysis plan will define exact comparators and age groups to be studied
 after reviewing baseline data.
Current asthma guidelines in the UK are underpinned by evidence derived from randomised
 controlled trials (RCTs). Although RCT data are considered the gold standard, patients
 recruited to asthma RCTs are estimated to represent less than 10% of the UK's asthma
 population. The poor representation of the asthma population is due to a number of factors,
 such as tightly-controlled inclusion criteria for RCTs. There is, therefore, a need for more
 representative RCTs and real-life observational studies to inform existing guidelines and
 help optimise asthma outcomes.

 The fixed combination asthma inhalers FP/SAL (as pMDI and DPI) and BUD/FOR (as DPI) are
 indicated for use in asthma when adequate asthma control is not achieved with low / medium
 dose ICS therapy and prn reliever therapy (a short-acting beta-agonist [SABA]). Fixed
 combination inhalers are also indicated in patients already adequately controlled on separate
 ICS/LABA therapy. However, emerging trends in asthma prescribing indicate increasing use of
 add-on therapies (particularly in the form of combination inhalers) in the early stages of
 asthma therapy, even as first-line therapy.

 The British Thoracic Society (BTS) Scottish Intercollegiate Guidelines Network (SIGN)
 guidelines on the management of asthma advise that there is no difference in efficacy between
 ICS/LABA therapy given as separate or combined inhalers. However, they do note that, once a
 patients is on stable therapy, combination inhalers have the advantage of guaranteeing that
 patients do not take their LABA without their ICS.

 In practice, there is significant pressure (supported by asthma guidelines) to use the least
 expensive, effective inhaled therapies available. While the effect of increased use of
 combination therapies in terms of patient benefits remains uncertain, the impact on treatment
 costs for the United Kingdom's (UK's) National Health Service (NHS) is unequivocal and, to
 date, there are limited data available as to the absolute and relative effectiveness of the
 ICS/LABA combination therapies currently licensed.

 There are a number of inhaler delivery devices available for use in asthma management.
 Whatever therapy is prescribed, optimal treatment response requires effective drug delivery
 within the airways; selecting the most appropriate delivery device for an asthma patient,
 therefore, plays an important role in optimising their asthma control. According to the
 recent BTS/SIGN guidelines, there is currently no evidence of a clinical difference in the
 effectiveness of therapy delivery via pMDI ± spacer compared with DPI in either adults or
 children, and more recent DPIs are rated as effective as older DPIs. Effective use of DPIs
 and pMDI requires entirely different inhalation techniques and there is some debate as to
 whether patients prescribed different device types for their reliever and preventer
 medication (requiring different techniques for each) may have poorer disease control than
 those prescribed the same device type for both preventer and reliever. Combining aerosols
 (e.g. pMDI preventer plus BAI reliever) is not considered to cause a problem in this respect.

 The aim of this study is to compare the absolute and relative effectiveness of currently
 licensed ICS/LABA combinations - FP/SAL and BUD/FOR (and their available delivery devices) -
 in children and adults with asthma whose therapy was changed or increased. Consideration will
 also be given to the effect of reliever therapy inhaler and the effect of consistency of
 device used (i.e. same or different devices for preventer and inhaler therapies) on asthma
 control outcomes. Also to be evaluated are the associated impact of inhaler technique review,
 recorded inhaler handling problems and use of a spacer in conjunction with a pMDI in terms of
 achieving asthma control outcomes.
Inclusion Criteria:

 -  Aged: 4-80 years: Paediatric cohort (aged 4-11 years); Adult cohort (aged 12-69
 years); Elderly cohort (aged 70-80 years.

 -  Evidence of asthma: i.e. a diagnostic code of asthma or ≥2 prescriptions for asthma at
 different points in time during the prior year, including one ICS prescription.

 -  Be on current asthma therapy: i.e. ≥1 asthma prescriptions in the prior year, and at
 least 1 other asthma prescription during the same period.

 -  Have at least one year of up-to-standard (UTS) baseline data (prior to the IPD) and at
 least one year of UTS outcome data (following the IPD).

 Exclusion Criteria:

 -  Diagnostic read code for chronic respiratory disease (including COPD) at any time

 -  On maintenance oral steroid therapy at baseline

 -  Any patients receiving a combination inhaler in addition to their separate ICS inhaler
 in the baseline year.