Asthma is one of the most common respiratory disorders in the UK. Leukotriene receptor antagonists (LTRAs) are a class of maintenance medications used in patients with mild to moderate chronic asthma. Although LTRAs have been on the market for two decades, little is known about the pattern of usage over time in the UK. Of note, there are two national guidelines on asthma in the UK: the British Thoracic Society/Scottish Intercollegiate Guideline Network (BTS/SIGN) guideline and the National Institute for Health and Care Excellence (NICE) guideline. However, the timing of introducing LTRAs is different between guidelines, and how they may have affected the utilization patterns of LTRAs is unclear.
Montelukast, the most widely used LTRA in the UK, has been associated with side effects that affect mental health and brain function. The United States Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA) have issued 3 warnings about the association and alerted healthcare professionals. Given the serious side effects including suicide, it is important to evaluate the impact of the warnings on the real-world practice of LTRAs prescribing.
Therefore, the purpose of this study is to understand the utilization patterns of LTRAs in the UK primary care and to evaluate any impact of the different treatment guidelines and drug safety warnings on LTRAs prescribing. This study will help to inform future studies of safety and effectiveness of medications in asthmatic patients.
Leukotriene receptor antagonists (LTRAs) are a class of maintenance medications used in patients with mild to moderate asthma and are prescribed primarily as adjunct therapy to inhaled corticosteroids (ICS). Although LTRAs have been on the market for two decades, little is known about the pattern of usage over time in the UK. In addition, there are factors that may impact on the utilization patterns of LTRAs.
First, there are two national guidelines on asthma in the UK: the British Thoracic Society/Scottish Intercollegiate Guideline Network (BTS/SIGN) guideline and the National Institute for Health and Care Excellence (NICE) guideline. One of the main differences between the two guidelines is the choice between introducing either LTRAs or long-acting beta2-agonist (LABA) after ICS. Second, the FDA and the MHRA have issued 3 drug safety warnings on the neuropsychiatric events of LTRAs.
Given these factors, this study will use data from January 2005 to December 2022 from CPRD linked to HES and ONS to describe the utilization patterns of LTRAs and to investigate whether the patterns have changed according to the treatment guidelines and safety warnings.
We will estimate the annual prevalence and incidence of LTRAs and the duration of LTRAs usage. To examine whether the LTRAs were initiated in accordance with the guidelines, we will assess the asthma control medications prescribed within one year before LTRAs initiation. We will also estimate the annual incidence of progression from ICS alone to 1) ICS+LTRA (NICE) and 2) ICS+LABA (BTS/SIGN), respectively; and the annual incidence of stepping up to the subsequent stage of therapy among patients on ICS+LTRA and ICS+LABA, respectively. Finally, the impact of the drug safety warnings on LTRAs prescribing will be evaluated using interrupted time series (ITS) analysis. This study will provide insight on the utilization patterns of LTRAs in the UK.
1. The annual prevalence and incidence of LTRAs prescribing
2. The duration of LTRAs usage
3. The asthma control medications prescribed within one year before LTRAs initiation
4. The annual incidence of progressing from ICS alone to ICS+LTRA or ICS+LABA
5. The annual incidence of stepping up to the subsequent stage of therapy among patients on ICS+LTRA and ICS+LABA
6. The changes in the LTRAs prescribing before and after the drug safety warnings
Wallis Lau - Chief Investigator - University College London ( UCL )
Boqing Chen - Corresponding Applicant - University College London ( UCL )
Kenneth Man - Collaborator - University College London ( UCL )
Yogini Jani - Collaborator - University College London ( UCL )
HES Accident and Emergency;HES Admitted Patient Care;HES Outpatient;ONS Death Registration Data;Patient Level Index of Multiple Deprivation;Practice Level Index of Multiple Deprivation