The FDA contraindicated using LABA as monotherapy in adults with asthma.
The use of long-acting beta2-agonists (LABA) as monotherapy in adult asthma patients was reduced after the US Food and Drug Administration contraindicated the practice although other prescribing patterns were less aligned with the agency’s Drug Safety Communications.
A longitudinal assessment, the study of prescribing patterns that followed from the FDA advisories, were issued as Drug Safety Communications, and incorporated into drug labeling.
In addition to contraindicating a LABA unless used concurrently with another agent to control asthma, the FDA indicated it could only be used for asthma that is not adequately controlled with an inhaled corticosteroid (ICS) or an asthma controller medication (ACM) such as a leukotriene modifier, chromone, oral systemic corticosteroid, immunomodulator, or methylxanthine.
To determine whether prescribing patterns have followed these recommended practices, the Division of Epidemiology of the FDA Center for Drug Evaluation and Research examined health plan claims data from 2003 to 2012. This period spanned the FDA regulatory actions on LABA use, from the boxed warnings of severe asthma exacerbations and death on the 2003 labeling of salmeterol (Serevent/ GlaxoSmithKline) to the 2010 Drug Safety Communications and subsequent product labeling advising on the safe use of LABA products in adult asthma treatment.
Study co-author Solomon Iyasu, MD, MPH (pictured), then Director of the Office of Pharmacovigilance and Epidemiology, and colleagues explained the importance of determining whether prescribing practices are congruent with issued advisories. "Overall, risk communications of medical products are important for patients using the products as well as for physicians prescribing them, yet such communications are rarely fully evaluated."
Iyasu and colleagues identified approximately one-half million adults with asthma who met inclusion criteria, with no LABA prescription within 6 months of the study initiation date, and no other indications for the treatment such as chronic obstructive pulmonary disease.
The congruence of prescribing with the first advisory, that the LABA be used with an ICS or ACM, was determined from finding concurrent prescriptions, and calculating a high "medication concurrency ratio" of the number of days on combined treatment relative to the total number of days with LABA monotherapy. The assessment of whether the LABA was added only after symptoms were not adequately controlled by an ICS or ACM was derived from the prior prescriptions, and claims identifying "poorly controlled asthma" or surrogate data such as hospital or emergency department admissions. Compliance with the step-down recommendation was extrapolated from shorter periods of continuous LABA treatment and extended durations of final refills.
The investigators found that the use of LABA monotherapy was reduced from over 9% prior to 2003 to less than 2% after the 2010 Drug Safety Communications. However, Iyasu and team described their other findings as "not as encouraging”.
The proportion of those receiving an ICS or ACM for several months and evidencing inadequate symptom control before commencing LABA did not increase after the advisories, yet the use of a LABA for longer than 4 months increased despite the recommendation to step down treatment to discontinuation.
Although the results were stratified for the time periods corresponding to each regulatory action and advisory, Iyasu and colleagues acknowledged that prescribing patterns were probably influenced by such other factors as consensus developments and the clinical literature. "Clinical practice and patient preferences could have been influenced by these factors and others, such as overall ACM effectiveness, adverse event experience, medication formulary changes, product advertising, insurance coverage, over-the-counter availability, out-of-pocket, and overall cost."
The study comparing prescribing patterns for adult asthma patients with FDA safety recommendations, “The US Food and Drug Administration’s Drug Safety Recommendations and Long Acting Beta2-Agonist Dispensing Pattern Changes in Adult Patients: 2003-2012,” was published on-line March 16 in the Journal of Asthma and Allergy.
The investigators reported results from a similar study in children and adolescents in 2014.