Clinicians ignore international guidelines on minimum effective dose for asthma

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A large UK study found that asthma patients were increasingly prescribed higher levels of treatment, often without clear clinical indication for such high doses, ignoring international guidelines that recommend clinicians find the minimum effective dose that can control symptoms.

The study, by Dr Chloe Bloom and colleagues at Imperial College London,  found that stepping-down medication doses did not increase asthma exacerbations and could significantly reduce medication costs.

Over 5.4m people receive asthma treatment in the UK and asthma medication comprises 13% of total primary care prescribing costs. Additionally, prolonged use and higher doses of asthma medications are associated with a higher risk for systemic adverse effects and high medication costs. To understand the symptoms, diagnoses, and prescription patterns, the researchers conducted a population-based observational study, accessing primary care electronic health records of 508,459 asthma patients treated in the UK between 2001-2017. Using clinical asthma codes, researchers then evaluated a cohort of regular asthma preventer users, analysing changes in prescribed asthma medications and subsequent health outcomes for 31,379 patients who were stepped down in their asthma medicine prescriptions. The cost impact of medication step-down was then calculated for the cohort using 2019 drug costs.

Inhaled corticosteroids (ICS) are the second most prescribed medication, suggesting the potential to reduce costs considerably with appropriate stepping-down among asthma patients. Additionally, stepping-down just half of all suitable patients on long-acting β agonist (LABA) medication could save around £17m, equivalent to 2% of the UK’s asthma budget. This research is only the second real-world study to compare stepped-down patients to controls and one of the major strengths is inclusion of a nationally representative study population and large sample size. However, the researchers were limited in their ability to track which prescribed medications were dispensed and adhered to, a question that may be important for future studies.

According to the authors, “Although stepping-down of treatment is recommended by clinical guidelines, we found that it happened infrequently. Stepping down ICS or add-on therapy did not appear to worsen health outcomes but did appear to result in significant cost savings.

Abstract
Background: Guidelines recommend stepping down asthma treatment to the minimum effective dose to achieve symptom control, prevent adverse side effects, and reduce costs. Limited data exist on asthma prescription patterns in a real-world setting. We aimed to evaluate the appropriateness of doses prescribed to a UK general asthma population and assess whether stepping down medication increased exacerbations or reliever use, as well as its impact on costs.
Methods and findings: We used nationwide UK primary care medical records, 2001–2017, to identify 508,459 adult asthma patients managed with preventer medication. Prescriptions of higher-level medication: medium/high-dose inhaled corticosteroids (ICSs) or ICSs + add-on medication (long-acting β2-agonist [LABA], leukotriene receptor antagonist [LTRA], theophylline, or long-acting muscarinic antagonist [LAMA]) steadily increased over time (2001 = 49.8%, 2017 = 68.3%). Of those prescribed their first preventer, one-third were prescribed a higher-level medication, of whom half had no reliever prescription or exacerbation in the year prior. Of patients first prescribed ICSs + 1 add-on, 70.4% remained on the same medication during a mean follow-up of 6.6 years. Of those prescribed medium/high-dose ICSs as their first preventer, 13.0% already had documented diabetes, cataracts, glaucoma, or osteopenia/osteoporosis. A cohort of 125,341 patients were drawn to assess the impact of stepping down medication: mean age 50.4 years, 39.4% males, 39,881 stepped down. Exposed patients were stepped down by dropping their LABAs or another add-on or by halving their ICS dose (halving their mean-daily dose or their inhaler dose). The primary and secondary outcomes were, respectively, exacerbations and an increase in reliever prescriptions. Multivariable regression was used to assess outcomes and determine the prognostic factors for initiating stepdown. There was no increased exacerbation risk for each possible medication stepdown (adjusted hazard ratio, 95% CI, p-value: ICS inhaler dose = 0.86, 0.77–0.93, p < 0.001; ICS mean daily = 0.80, 0.74–0.87, p < 0.001; LABA = 1.01, 0.92–1.11, p = 0.87, other add-on = 1.00, 0.91–1.09, p = 0.79) and no increase in reliever prescriptions (adjusted odds ratio, 95% CI, p-value: ICS inhaler dose = 0.99, 0.98–1.00, p = 0.59; ICS mean daily = 0.78, 0.76–0.79, p < 0.001; LABA = 0.83, 0.82–0.85, p < 0.001; other add-on = 0.86, 0.85–0.87, p < 0.001). Prognostic factors to initiate stepdown included medication burden, but not medication side effects. National Health Service (NHS) indicative prices were used for cost estimates. Stepping down medication, either LABAs or ICSs, could save annually around £17,000,000 or £8,600,000, respectively. Study limitations include the possibility that prescribed medication may not have been dispensed or adhered to and the reason for stepdown was not documented.
Conclusion: In this UK study, we observed that asthma patients were increasingly prescribed higher levels of treatment, often without clear clinical indication for such high doses. Stepping down medication did not adversely affect outcomes and was associated with substantial cost savings

Authors
Chloe I Bloom, Laure de Preux, Aziz Sheikh, Jennifer K Quint

PLOS Medicine abstract

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