UK Study Finds Off-Label Prescribing of COPD Therapies Is Low

Skylar Jeremias

Two therapeutic regimens used for the treatment of chronic obstructive pulmonary disease (COPD) are rarely being prescribed to patients without a COPD diagnosis, investigators concluded.

A recent study on prescribing patterns for umeclidinium bromide (UMEC) and umeclidinium and vilanterol (UMEC/VI) found that both regimens are being prescribed appropriately for the treatment of chronic obstructive pulmonary disease (COPD).

The retrospective, multi-database, observational study, published in the International Journal of Chronic Obstructive Pulmonary Disease, is the first to investigate if general practitioners are prescribing UMEC or UMEC/VI off label since the regimens were approved for use in the European Union in 2014.

UMEC is a long-acting muscarinic antagonist (LAMA) monotherapy and UMEC/VI is a dual therapy consisting of a LAMA and long-acting beta-agonist (LABA). The Global Initiative for Chronic Obstructive Lung Disease recommends the use of LAMA or LABA monotherapy as an initial maintenance therapy for most patients with COPD. In cases of more severe COPD or exacerbations, patients can receive a dual or triple therapy (LAMA/LABA/inhaled corticosteroid).

The investigators set out to quantify off-label prescribing, evaluate real-world safety outcomes, and assess treatment adherence among new users of UMEC and UMEC/VI by examining 2 UK electronic health record databases. The study population included patients newly prescribed UMEC, UMEC/VI, or another long-acting bronchodilator (LABD) in the United Kingdom between July 1, 2014 and June 30, 2016. Treatment adherence and safety outcomes were assessed for 12 months.

The study had 2 cohorts: the primary care cohort and the linked cohort. The primary care cohort consisted of eligible patients entered into the databases used in the study. The linked cohort included a subset of patients from one of the databases who were linked to 2 other datasets to allow for investigators to assess outcomes detected or treated in a hospital inpatient setting and mortality rates.

In the primary care cohort, there were 3875 new users of UMEC, 2224 new users of UMEC/VI, and 32,809 new users of other LABDs. The mean (SD) time to follow-up was 565.3 (268.6) days. The linked cohort included 547 new users of UMEC, 512 new users of UMEC/VI, and 10,590 new users of other LABD, and had a mean (SD) follow-up time of 493.3 (286.1) days.

Off-label use of UMEC and UMEC/VI was expected to be low because most patients had a COPD diagnosis. In the primary care cohort, off label prescribing was considered possible for 7.0% of UMEC users and 8.8% of UMEC/VI users compared with 18.0% of other LABD users.

Asthma diagnosis accounted for 130 (3.4%) of UMEC users and 69 (3.1%) UMEC/VI users, of whom 34 UMEC users and 39 UMEC/VI users were not receiving a concomitant therapy, suggesting possible off-label usage. Overall, possible off-label prescribing among patients with asthma accounted for 0.9% of all UMEC users and 1.8% of all UMEC/VI users.

Additionally, concomitant therapy was less common in the subgroup of patients without a diagnosis of COPD or asthma compared with patients with either diagnosis.

In both cohorts, the incidence rates (IRs) for cardiovascular outcomes were as expected and similar between UMEC and UMEC/VI users, even among those who did and did not receive concomitant therapy, suggesting that the safety profile of the regimens remains unchanged. The IRs for pneumonia and moderate acute exacerbations of COPD were higher among users for UMEC and UMEC/VI in the primary care cohort.

Overall, 105 (2.7%) of UMEC users and 62 (2.8%) of UMEC/VI users died. Mortality was slightly more common in the linked cohort than the primary care cohort.

When applying the 80% or greater mediation possession ratio definition for treatment adherence, 62.8% (n = 1734) of new users of UMEC and 64.3% (n = 921) of new users of UMEC/VI were consistently using the therapy prescribed to them at the beginning of the study period.

The investigators identified the use of data solely sourced from the United Kingdom as a limitation because the results likely can’t be generalized to other countries or regions. Also, some patients did not have a recorded diagnosis, which could have skewed the real number of patients with a diagnosis for COPD or asthma.

“Moreover, prescribed medications might not have been dispensed at the pharmacy or utilized by the patient. As such, this study is only able to assess off-label prescribing and cannot make strong inferences about off-label use,” wrote the investigators.

Reference

Requena G, Dedman D, Quint JK, Ghosh RE, Williams R, Pimenta JM. The utilization and safety of umeclidinium and umeclidinium/vilanterol in UK primary care: A retrospective cohort study. Int J Chron Obstruct Pulmon Dis. Published online March 10, 2021. Accessed March 29, 2021. doi:10.2147/COPD.S291931