Real-world Effectiveness and Cost-effectiveness of Leading Inhaled Corticosteroids in Asthma Management

Study Overview
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Brief Summary
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The objective of the study was to compare the effectiveness, cost-effectiveness and direct healthcare costs of managing asthma in patients with evidence of persistent asthma, following the initiation and increased dose of inhaled corticosteroid (ICS) therapy using HFA-BDP (Qvar®) (either as initial therapy or as a step-up therapy) compared with the most commonly prescribed alternative ICS in the UK, CFC-beclometasone (BDP) and fluticasone (FP) as metered dose inhalers (MDIs). Qvar vs FP analyses were split between adults (12-60yrs) and paediatrics (5-11yrs).

Detailed Description
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While current UK asthma guidelines are underpinned with evidence from RCTs, much of this evidence has been undertaken in patients who are not representative of the majority of the current UK asthma population. In fact it has been estimated that fewer than 10% of the patients seen in everyday clinical practice would be eligible for inclusion in such trials. 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 and observational studies to inform existing guidelines and help optimise asthma outcomes. A more holistic approach to respiratory research would see RCT evidence complimented by real-life data from pragmatic trials and observational studies. A number of trends are emerged in asthma prescribing that warrant further investigation to ascertain their benefit to both the patient and the NHS. In particular, significant pressure exists to use the cheapest inhaler devices and formulations. An analysis of a pragmatic trial of Qvar versus standard CFC-BDP undertaken by Research in Real Life suggested that Qvar may be offer greater effectiveness in.5,6 In light of these data, the following report details the findings of a study designed to examine the effectiveness of Qvar in real-life clinical practice using the General Practice Research Database (GPRD).

Official Title
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A Retrospective Evaluation of the Effectiveness and Cost-effectiveness of HFA-BDP MDI (Qvar®) Compared With CFC-BDP MDI and FP MDI Used in the Management of Asthma in a Representative UK UK Primary Care Population

Conditions
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Asthma

Intervention / Treatment
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* Drug: Extra-fine hydrofluoroalkane-beclomethasone dipropionate
* Drug: Extra-fine hydrofluoroalkane-beclomethasone dipropionate
* Drug: Fluticasone propionate
* Drug: Beclomethasone dipropionate
* Drug: fluticasone propionate
* Drug: Chlorofluorocarbon beclomethasone dipropionate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Included patients must: aged 5-60 years evidence of asthma: a diagnostic code of asthma or ≥2 prescriptions for asthma in baseline year at different points in time including one of ICS on current therapy at the IPD, defined as ≥1 ICS script and ≥1 other asthma prescriptions in the 12 months prior to first change in therapy had definite dosing instructions have at least 1 year of up-to-standard (UTS) baseline data before IPD have at least 1 year of UTS outcome data after 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 For the therapy increase patient cohort, any patients receiving a combination inhaler in addition to their separate ICS inhaler in the year prior to IPD were also excluded.

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 60 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 |
| --- | --- |
| IPDI HFA-BDP MDI<br>Patients who commenced inhaled corticosteroid therapy as HFA-BDP via MDI | Drug: Extra-fine hydrofluoroalkane-beclomethasone dipropionate<br>* Initiation of HFA-BDP (any dose) in steroid naive patients via MDI<br>* Other names: Qvar®;|
| IPDI FP MDI<br>Patients who commenced inhaled corticosteroid therapy as FP via MDI | Drug: fluticasone propionate<br>* Initiation of FP (any dose) via MDI in steroid naive patient<br>|
| IPDA FP MDI<br>Patients who had a step up in inhaled corticosteroid therapy as FP via MDI | Drug: Fluticasone propionate<br>* An increase in the baseline BDP-equivalent dose of inhaled corticosteroid as FP via MDI<br>|
| IPDA HFA-BDP MDI<br>Patients who had a step up in inhaled corticosteroid therapy as HFA-BDP via MDI | Drug: Extra-fine hydrofluoroalkane-beclomethasone dipropionate<br>* An increase in the baseline BDP-equivalent dose of inhaled corticosteroid as HFA-BDP via MDI<br>* Other names: Qvar;|
| IPDI CFC-BDP MDI<br>Patients who commenced inhaled corticosteroid therapy as CFC-BDP via MDI | Drug: Chlorofluorocarbon beclomethasone dipropionate<br>* Initiation of CFC-BDP (any dose) via MDI in steroid naive patient<br>|
| IPDA CFC-BDP MDI<br>Patients who had a step up in inhaled corticosteroid therapy as CFC-BDP via MDI | Drug: Beclomethasone dipropionate<br>* An increase in the baseline BDP-equivalent dose of inhaled corticosteroid as CFC-BDP via MDI<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proxy asthma control | Primary composite measure asthma control defined as: 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 |
| --- | --- | --- |
| Revised asthma control | A revised definition of proxy asthma control for sensitivity analysis was defined as: No recorded hospital attendance for asthma including admission, A&E attendance, out of hours attendance or 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 Average daily prescribed dose of salbutamol of no more than 200mcg and terbutaline 500mcg. | One-year outcome period | 
| Disaggregated components of the primary control outcome | Hospital admissions for asthma Consultations and hospital attendances for LRTI requiring antibiotics Prescriptions for oral steroids SABA use | One-year outcome period | 
| Time to the first asthma exacerbation | Where an exacerbation is defined as: An occurrence of unscheduled hospital admission/A&E attendances for asthma AND/OR Use of oral steroids. | One-year outcome period | 
| Success of the therapeutic regimen | Defined as: Exacerbation AND/OR Increase in dose of ICS AND/OR Change in ICS drug type AND/OR Change in delivery device AND/OR Use of additional therapy as defined by: LABAs, oral steroids, theophylline, leukotriene receptor antagonists (LTRAs) | One-year outcome period | 
| Use of anti-fungals | defined as incidences of definite oral candidiasis | One-year | 
| Daily dose of ICS (BDP equivalent) at week 52 compared with week 0 and proportion on original dose of BDP Daily dose* of ICS (BDP equivalent) at week 52 compared with week 0 and proportion on original dose of BDP. | BDP-equivalent dose were calculated by multiplying the Qvar and FP doses by a factor of 2. The dose at week 52 was compared with that at week 0 in order to identify the proportion of original (week 0) ICS dose. | 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, Beclomethasone dipropionate, Fluticasone propionate, Metred dose inhaler, Extra-fine hydrofluoroalkane, Chlorofluorocarbon