Real-world Effectiveness and Cost-effectiveness of HFA-beclometasone Compared With ICS/LABA Combination Therapy

Study Overview
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Brief Summary
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This study will compare the effectiveness, cost-effectiveness and direct healthcare costs of asthma management in patients with evidence of persistent asthma following an increase in asthma therapy in the form of either an increased dose of inhaled glucocorticosteroids (ICS) using extrafine hydrofluoroalkane-beclometasone dipropionate (HFA-BDP) via pressurised metered-dose inhaler (pMDI) or breath-actuated inhaler (BAI), or a change to combination ICS plus long-acting bronchodilator (LABA) therapy using fixed combinations (fluticasone propionate / salmeterol [FP/SAL] or budesonide / formoterol [BUD/FOR]) or separate pMDIs and BAIs.

Detailed Description
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Current asthma guidelines in the UK are underpinned by evidence derived from randomised controlled trials (RCTs). Although RCT data are considered the gold standard, the patients recruited to asthma RCTs are estimated to represent less than 10% of the United Kingdom's (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 (Seretide) and BUD/FOR (Symbicort) are indicated for use in asthma when adequate asthma control is not achieved with low/medium dose ICS therapy and as-needed (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. 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 add-on and combination therapies in terms of patient benefits remains uncertain, the impact on the UK's National Health Service (NHS) treatment costs is unequivocal. Short, randomised trials of the effectiveness of asthma monotherapies have demonstrated that extrafine HFA-BDP is at least as effective at half the dose as BDP pMDI, and equivalent to same-dose FP pMDI. There is also evidence to suggest that extrafine HFA-BDP optimises deposition in the lung and affords greater tolerance of poor coordination of breathing and inhaler actuation. In addition, one long-term, prospective, randomised, open-labelled trial comparing extrafine HFA-BDP with BDP over the course of one year demonstrated greater improvements in symptom-free days and quality of life in the extrafine HFA-BDP treatment group, at a lower cost per symptom-free day. The hypothesis for this study, therefore, is that extrafine HFA-BDP may be a suitable, and cost-effective, alternative to combination therapy (as fixed or separate inhalers) in children and adults with evidence of persistent asthma.

Official Title
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A Retrospective Evaluation of Effectiveness and Cost-effectiveness of Extrafine HFA-BDP Compared With Combination ICS/LABA Therapy in the Management of Asthma in a Representative Population of UK Primary Care Patients

Conditions
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Asthma

Intervention / Treatment
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* Drug: Extra-fine hydrofluoroalkane-beclometasone dipropionate
* Drug: ICS / LABA via separate pMDI and / or BAI inhalers


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged: 4-60 years: Paediatric cohort (aged 4-11 years), and Adult cohort (aged 12-60 years) Aged 61-80 years and never smoked for an additional elderly cohort; Evidence of asthma: i.e. a diagnostic code of asthma or at least 2 asthma prescriptions, including one ICS prescription, at different points in time during the year prior to IPD (the baseline year) Be on current asthma therapy: i.e. at least 1 asthma prescription in the year prior to IPD, 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: had a diagnostic read code for chronic obstructive pulmonary disease (COPD) at any time had a diagnostic read code for chronic respiratory disease at any time (other than asthma) any patients receiving a combination inhaler in addition to their separate ICS inhaler in the baseline year

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Step-up as FDC ICS/LABA<br>ICS asthma patients who increased therapy as FDC ICS/LABA (no increase in daily ICS dose). | |
| Step up as separate therapies<br>ICS asthma patients who increased therapy as ICS / LABA via separate pMDI and / or BAI inhalers (no increase in daily ICS dose). | Drug: ICS / LABA via separate pMDI and / or BAI inhalers<br>* A step-up from baseline ICS therapy via the addition of a separate long-acting beta-agonist with no change in baseline ICS drug or dose<br>* Other names: ICS+LABA separates;|
| Qvar step-up<br>ICS asthma patients who increased therpy as extra-fine hydrofluoroalkane-beclometasone dipropionate | Drug: Extra-fine hydrofluoroalkane-beclometasone dipropionate<br>* Increase in the baseline BDP-equivalent dose of inhaled corticosteroid as HFA-BDP via pMDI or BAI<br>* Other names: Qvar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proxy asthma control | No recorded hospital attendance for asthma including admission, Accident & Emergency (A&E) attendance, out of hours attendance or Out-Patient Department (OPD) attendance, AND No prescriptions for oral steroid, AND No consultations, hospital admissions or A&E attendance for lower respiratory tract infections (LRTI) requiring antibiotics | One-year outcome period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Success of therapeutic regimen | Defined as the absence of (i) Exacerbation: Unscheduled hospital admissions / A&E attendance for asthma, OR Acute use of oral steroids AND (ii) No consultations, hospital admissions or A&E attendance for LRTI requiring antibiotics AND (iii) No change in therapeutic regimen: Increased dose of ICS, and/or Change in ICS/LABA, and/or Change in delivery device, and/or Use of additional therapy as defined by: theophylline, LTRAs, oral beta agonists (or LABAs in patients receiving extrafine HFA-BDP). | One-year outcome period | 
| Success of therapeutic regimen (sensitivity - independent of cost saving) | Success: defined as the absence of (i) Exacerbation: Unscheduled hospital admissions / A&E attendance for asthma, OR Acute use of oral steroids AND (ii) No consultations, hospital admissions or A&E attendance for lower respiratory tract infections (LRTI) requiring antibiotics AND (iii) No change in therapeutic regimen: Increased dose of ICS, and/or Use of additional therapy as defined by: theophylline, leukotreine receptor antagonists (LTRAs), oral beta agonists (or LABAs in patients receiving extrafine HFA-BDP). | One-year outcome period | 
| average SABA daily dose during outcome year | Average daily dose categorised as: 0mcg, >0-100mcg, >100-200mcg, >200-400mcg, >400-800mcg, >800mcg). | One-year outcome period | 
| Hospitalisations | Mean number of asthma and respiratory-related hospitalisations recorded per patient during the outcome year | One-year outcome period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Primary care, Asthma management, Inhaled corticosteroids, Extra-fine hydrofluoroalkane, Long-acting beta-agonist, Fixed-dose combination therapy