Real-world Effectiveness of Combination Therapy in Asthma
Condition: Asthma
MeSH terms: Asthma
Study type: Observational

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Fluticasone / formoterol metered dose inhaler; Fluticasone / salmeterol dry powder inhaler; Budesonide / formoterol dry powder inhaler; Fluticasone / salmeterol dry powder inhaler; Fluticasone / salmeterol metred dose inhaler; BUD/FOR dry powder inhaler
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): Prescribed at the same BDP-equivalent dose as baseline ICS; Prescribed at the same BDP-equivalent dose as baseline ICS; Prescribed at the same BDP-equivalent dose as baseline ICS; Prescribed at ≥twice BDP-equivalent dose as baseline ICS; Prescribed at ≥twice BDP-equivalent dose as baseline ICS; Prescribed at ≥twice BDP-equivalent dose as baseline ICS
Other intervention name(s): Seretide MDI; Seretide DPI; Symbicort DPI; Seretide DPI; Seretide MDI; Symbicort DPI
Intervention MeSH terms: Fluticasone; Xhance; Budesonide; Formoterol Fumarate; Salmeterol Xinafoate; Fluticasone-Salmeterol Drug Combination; Budesonide, Formoterol Fumarate Drug Combination
Observational model: Cohort
Time perspective: Retrospective
Sampling method: Non-Probability Sample
Study population: 
        Primary care asthma patients receiving ICS therapy (any of BDP, extrafine HFA-BDP, BUD or
        FP as pMDI, BAI or DPI) plus as needed SABA reliever therapy who underwent a change in
        asthma therapy to combination ICS/LABA therapy as FP/SAL (MDI or DPI) or BUD/FOR (DPI) at
        the same or at least twice the BDP-equivalent dose of ICS prescribed during baseline.
      
Keywords: Primary care; Asthma management; Combined therapy; Real-world; Effectiveness; Control; Exacerbations