Asthma is a prevalent chronic condition affecting 5-10% of the general population. In patients with asthma, the airways – via inflammation – might narrow, swell, and produce extra mucus. Unfortunately, asthma cannot yet be cured but the symptoms can be controlled. Medical therapy in asthma consists of anti-inflammatory drugs (mainly inhaled corticosteroids (ICS)) and bronchodilators (drugs to open the airways e.g.B2 agonists or muscarinic antagonists). Asthma treatment is tailored via a step-up or step-down approach. In patients with uncontrolled asthma, despite treatment with medium dose ICS in combination with a long acting B2 agonist (LABA), guidelines suggest to either (1) increase to high dose ICS+LABA or (2) add a long acting muscarinic antagonist (LAMA) on top of medium dose ICS+LABA. Physicians might (3) not only increase the dose of ICS but also add a LAMA resulting in triple therapy of high dose ICS+LABA+LAMA. It is unknown which patients benefit most from the treatment options as described above.
As the optimal goal is to tailor asthma treatment to the individual needs of the patient (i.e. personalized care) we want to explore i) the main drivers of prescribing of any of the three step-up treatment options and ii) to identify patient characteristics that are associated with treatment response. Treatment response is defined as an improvement of lung function and/or a decrease in the frequency of severe asthma exacerbations. This research will be conducted using the CPRD database and defining a cohort of asthma patients, treated with medium dose ICS+LABA requiring treatment step-up.
Background:
In patients with uncontrolled asthma treated with medium dose ICS/LABA, GINA guidelines recommend to either increase to high dose ICS/LABA or to start triple therapy consisting of medium dose ICS/LABA+LAMA. Although adding LAMA on top of high dose ICS+LABA is not recommended by GINA for this step, it is likely that this regimen is also initiated in the real world.
Aims:
To study the main drivers of prescribing any of the three step-up treatment options and to determine patient characteristics that are associated with treatment response to the specific treatment regimens.
Outcomes:
Asthma Treatment response is defined as a ≥25% reduction in the annual severe asthma exacerbation rate following treatment step-up compared to the exacerbation rate in the 12 months prior to follow-up and/or improvement of ≥7.5% of FEV1% compared to baseline FEV1% in combination with an absolute improvement of FEV1 compared to baseline of 100 mL.
Severe asthma exacerbation is defined as use of acute systemic corticosteroids, ED visit, and/or hospitalisation for reasons of asthma exacerbation. Hospital Episode Statistics (HES) data will be used to determine hospitalisations due to severe asthma exacerbation.
Methods:
We will include patients diagnosed with asthma, aged 18-65 years with at least 1 year of database history. Within this cohort, we will include patients prescribed medium dose ICS+LABA and requiring treatment step-up (high dose ICS+LABA, medium dose ICS+LABA+LAMA or high dose ICS+LABA+LAMA). The study period is from 2010-2020.
Descriptive statistics will be used providing numbers, proportions, medians and interquartile range to describe the total number of patients with asthma, patient characteristics in the respective treatment step-up cohorts, discontinuation, and switching patterns. Within each treatment cohort, logistic regression will be run with outcome treatment response. Cluster analysis will be conducted, in each treatment cohort separately using characteristics at index date and response characteristics.
The following outcomes will be investigated:
Asthma treatment response: Response is defined as a ≥25% reduction in severe asthma exacerbation rate (in the 12 months follow-up from treatment step-up) compared to the exacerbation rate in the 12 months prior to treatment step-up
AND/OR
improvement of ≥7.5% of FEV1% compared to baseline FEV1% in combination with an absolute improvement of FEV1 compared to baseline of 100 mL. (with a sensitivity analysis for improvement of 50 mL).
To define treatment response, information on lung function and information on severe asthma exacerbations is important. A severe asthma exacerbation is defined as use of acute systemic corticosteroids, ED visit, and/or hospitalisation for reasons of asthma exacerbation.(1)
Treatment patterns: (treatment discontinuation, treatment step-down or switch). Patients will be considered as discontinuing GINA treatment step-up in case the respective treatment discontinues or in case there is more than 60 days between two episodes of the same GINA treatment step-up. The number of patients discontinuing treatment will be described (proportion of total number of asthma individuals being treated) and these patients will be further characterized as number of patients with “treatment discontinuation”, “treatment step down” or “treatment switch” to another category of GINA treatment step-up.
Health care resource use: The number of GP (outpatient) office visits (excluding telephone requests for repeat prescriptions only) and home visits in the year prior to the start of follow-up will be considered and will be compared to those in the one year following treatment step-up.
SABA (short acting B2 agonists) use and short course OCS (oral corticosteroid) use: The number of prescriptions of SABA and short course OCS use in the year prior to the start of follow-up will be considered and will be compared to those in the one year following treatment step-up. Use of SABA and OCS will be extracted based on an automated search on the respective BNF codes. Short course OCS use is defined as use of OCS for a consecutive period of less than 30 days.
Daniel Prieto-Alhambra - Chief Investigator - University of Oxford
Eng Hooi Tan - Corresponding Applicant - University of Oxford
Antonella Delmestri - Collaborator - University of Oxford
Katia Verhamme - Collaborator - Erasmus University Medical Center ( EMC )
HES Admitted Patient Care