For Optimal Cost-effectiveness, Strategize Biologic Therapy for Severe Asthma

There are multiple factors to think about when deciding if a patient with severe asthma is the most appropriate candidate for the therapy, according to a live session presented Sunday at the American College of Allergy, Asthma & Immunology Annual Scientific Meeting.

Asthma is a notoriously expensive disease, noted John Oppenheimer, MD, a director of clinical research at Pulmonary and Allergy Associates and clinical professor of medicine at University of Medicine and Dentistry of New Jersey-Rutgers.

"And what's disturbing is we often don't discontinue medicines that are ineffective and each one of them cost more and more money," he said during his presentation, "Economic Outlook for Biologics in Asthma–Are They Cost-Effective?"

Some studies have reported the prevalence of uncontrolled asthma in the range of 40% to 60%. A recent study found that 53% of patients in 12 pulmonary clinics and 12 allergy clinics had asthma that was not well controlled, but no physician wants to think about the possibility that half of their patients have uncontrolled asthma, Oppenheimer said.

The consequences of uncontrolled asthma include increased risk of exacerbations, worse health-related quality of life, and increased health care utilization and costs. A 2019 study estimated that indirect and direct costs will approach about $1 trillion over the next 20 years, he said.

Asthma has many differences in phenotype, age of onset, triggers, pathobiology, severity, presence of chronic airway obstruction, and disease course. Yet current clinical guidelines don’t lay out a path by phenotype.

Instead, Oppenheimer noted, “our approach is, when somebody has severe uncontrolled asthma, we throw the kitchen sink at them, correct? We just keep escalating medicines more and more and more. And what's disturbing is we often don't discontinue medicines that are ineffective and each one of them cost more and more money.”

The first study to look at individual response to therapy, the Best Add-on Therapy Giving Effective Responses (BADGER) trial, was published in 2010. Investigators assessed the frequency of differential responses to 3 blinded step-up treatments in children who had uncontrolled asthma while receiving low-dose inhaled corticosteroids (ICS)—100 mcg of fluticasone twice daily—using a 3-way crossover design with a composite of outcomes (asthma exacerbations, asthma-control days, and forced expiratory volume in 1 second).

The blinded step-up therapies, in random order for 16 weeks, consisted of 250 mcg of fluticasone twice daily (ICS step-up), 100 mcg of fluticasone plus 50 mcg of a long-acting beta-agonist twice daily (LABA step-up), or 100 mcg of fluticasone twice daily plus 5 or 10 mg of a leukotriene-receptor antagonist daily (LTRA step-up).

A differential response occurred in 161 of 165 patients; the response to the LABA was most likely to be the best response, but patients also responded to other treatments as the best outcome. Higher scores on the Asthma Control Test predicted a better response to LABAs, as did White race, while Black patients were equally likely of having a best response to LABA or ICS step-up therapy and were least likely to have a best response to LTRA step-up therapy.

Eleven years after the study was published, Oppenheimer said, the field still does not know enough about which patient will respond to a particular therapy, or not.

“The elephant in the room is, we have to balance therapeutic costs with outcomes,” he said.

Referring to a 2019 paper looking at the cost-effectiveness of biologics for asthma that said prices would have to be reduced by 60%, Oppenheimer suggested that cost-effectiveness could be improved if providers knew in advance which patient would respond.

There are some clues to those questions in existing studies, he indicated; the reports delve into issues around adherence, including those with errors in using their current inhaled medications or not filling prescriptions; comorbidities, such as rhinitis; home administration of a biologic, since that is less expensive than administering in an office; and the timing of asthma flares, such as seasonal exacerbations in September, among other things.

Reference

Oppenheimer J. Economic outlook for biologics in asthma–are they cost-effective? Presented at: ACAAI 2021 Annual Scientific Meeting; November 4-8, 2021; New Orleans, LA.