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Asthma: Long-acting Muscarinic Antagonists Overused, Up Exacerbation Risk


Long-acting muscarinic antagonists, recommended as add-on therapy for asthma, are too often used as monotherapy and are linked with severe exacerbations, a new study finds.

Long-acting muscarinic antagonists (LAMA) are frequently prescribed outside of recommended treatment guidelines for patients with asthma, according to a new study presented at the recent virtual European Respiratory Society 2020 Congress.

The data, presented by a research team from the Netherlands and Belgium, revealed use of LAMA monotherapy among approximately 40% of study patients with asthma, despite its indication for add-on use only.

To assess the prevalence of LAMA monotherapy in patients with asthma and the potential association with severe asthma exacerbations, investigators, led by Esme Baan, MD, of the Department of Medical Informatics at the Erasmus University Medical Center in the Netherlands, conducted a cohort analysis of patients from the longitudinal observational Integrated Primary Care Information (IPCI) database which collects electronic health record data from general practitioners in the Netherlands. Patients were aged 6 to 50 years with a diagnosis of asthma who were reportedly using LAMA therapy during follow-up.

Asthma treatment periods were stratified by either monotherapy LAMA, double therapy (LAMA plus inhaled corticosteroid [ICS]), or triple therapy (LAMA + ICS + long-acting beta agonist [LABA]).

Patient characteristics were collected at the beginning of each treatment period and included age, sex, history of exacerbations, and comorbidities. Poisson regression analysis was applied to calculate the relative rate (RR) of severe asthma exacerbations, with an adjustment for patient characteristics.

Median patient age was 41 years old and two-thirds (65.9%) were women.

  • Of the 3596 observed LAMA treatment periods, 1390 (38.7%) were considered LAMA monotherapy; 553 (15.4%) were identified as double therapy, and 1653 (46.0%) triple therapy.
  • Among all patients on LAMA therapy, a relative severe asthma exacerbation risk of 1.58 (95% CI, 0.52 – 4.77; P = .42) was observed among those receiving monotherapy vs double therapy.
  • When patients who had used triple therapy were excluded, the relative risk of severe exacerbations increased to 5.72 (95% CI, 1.39 – 23.62; P = .02).
  • Other notable relative risks for severe exacerbation across all patients included being female (RR, 1.63; 95% CI, 1.10 – 2.42; P = .016) and a history of previous exacerbations (RR, 1.81; 95% CI, 1.63 – 2.00; P <.001).

The findings, Baan and colleagues conclude, point to an overreliance on LAMA as sole maintenance therapy for asthma vs its recommended use as an add-on treatment.

“This observational study shows that LAMA is frequently prescribed as monotherapy (ie, without concurrent ICS) which is associated with an increased risk of exacerbations,” they wrote. “This emphasizes the need to check for ICS use when prescribing LAMA to asthmatic patients.”

The study, “(in)Appropriate LAMA Prescribing in Asthma patients: a Cohort Analysis (the ALPACA study),” was presented at ERS 2020.

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