Most patients escalated to asthma biologics did not adhere to prior maintenance treatment

Key takeaways:

• Clinicians should assess their asthma patients for adherence to their maintenance medication before escalating them to biologic treatment.
• 63% of patients had suboptimal adherence to their maintenance medication in the 12 months before biologic treatment was initiated.
• Biologics increase the annual costs of asthma control from $14,071 to $34,887.

About two-thirds of patients who began biologics for asthma exacerbations had suboptimal adherence to maintenance medication in the prior year, according to a study published in The Journal of Allergy and Clinical Immunology: In Practice.

Improved monitoring of medication adherence could reduce inappropriate escalations to biologics and reduce costs, John Oppenheimer, MD, clinical professor of medicine at UMDNJ Rutgers University School of Medicine, and colleagues wrote in the study.

John Oppenheimer

“The addition of biologic agents in the care of asthma has been a great aid in our care of poorly controlled asthmatics. Multiple publications have questioned their cost and appropriate use,” Oppenheimer, who also is an allergist at Pulmonary and Allergy Associates NJ and a Healio Allergy/Asthma Peer Perspective Board Member, told Healio, adding that biologic therapy is not a replacement for adherence.

Oppenheimer noted one study where patients who discontinued biologic therapy experienced exacerbation rates that were similar to matched controls who continued biologic therapy. Yet other studies have shown exacerbation rates increasing when biologics were discontinued.

“Our intent was to delve into the data further to better understand what patients were using biologic agents,” Oppenheimer said.

Recommendations for treatment

According to Global Initiative for Asthma (GINA) guidelines, clinicians should treat patients at the lowest step that controls symptoms and prevents exacerbations and only consider escalating treatment to the next step if the asthma remains uncontrolled despite adequate adherence to maintenance medication and/or environmental remediation.

Biologics only are recommended for patients with exacerbations or poor symptom control despite high doses of inhaled corticosteroids (ICS) or long-acting beta 2 agonists (LABA) and for patients with allergic or eosinophilic biomarkers or who need maintenance oral corticosteroid (OCS) treatment.

But with cost-effectiveness ratios ranging from $325,000 to $391,000 per quality-adjusted life-year gained, the researchers cautioned that the price of biologics exceeds their cost-effectiveness, so clinicians should assess treatment necessity and how well patients are adhering to previous treatment before escalation.

“The biologic agents have proven to generally be quite safe,” Oppenheimer said. “In the future, I suspect that these agents will move to an earlier step in the algorithm of care as prices come down. However, presently with an average wholesale price of over $30,000 per year, their misuse could bankrupt the system.”

The study’s results

The retrospective, observational study included 506 adults (69% women) with at least one diagnosis of asthma who were escalated to biologic use between January 2016 and June 2020.

Before biologic initiation, uncontrolled asthma was present in 55% of the patients based on the European Respiratory Society and American Thoracic Society (ERS/ATS) definition and in 70% of the patients based on the Stempel definition.

With 71% of patients insured by a commercial payer, treatments in the 12 months before biologic initiation included ICS-LABA (66%), short-acting beta 2 agonists (SABAs; 62%), OCS (66%) and leukotriene receptor antagonists (LTRAs; 56%).

Overall, 80% of the patients had received ICS, ICS-LABA, LABA, long-acting muscarinic antagonists (LAMA), xanthines, LTRA or ICS-LABA-LAMA asthma maintenance therapy in the 12 months before biologic initiation.

When the researchers inferred which GINA steps that 395 of the patients had reached, 30% were at step 2, 2% were at step 3, 21% were at step 4 and 25% were at step 5, indicating that even patients with mild asthma were advanced to biologic therapy before other step management strategies were attempted to achieve asthma control.

The researchers categorized suboptimal adherence to biologics as a proportion of days covered (PDC) — or the ratio of days the patient was supplied with at least one maintenance medication during the assessment period to the total assessment duration of 12 months — of less than 80%.

Based on this threshold, 63% of patients had suboptimal adherence to their maintenance medication in the 12 months before biologic initiation, with a mean PDC during this period of 59%. Also, 55% of patients did not reach a mean PDC of less than 70%, 50% did not reach a mean PDC of less than 60% and 43% did not reach a mean PDC of less than 50%.

When the researchers analyzed the patients on GINA steps 4 or 5, they found that 57% did not reach a mean PDC of less than 80% and therefore had suboptimal adherence.

The patients with suboptimal adherence included 61% with uncontrolled asthma based on the ERS/ATS criteria and 77% based on the Stempel criteria. Among the patients who had optimal adherence, 74% met the ERS/ATS criteria and 92% met the Stempel criteria for uncontrolled asthma before starting biologic treatment.

Also, 29% of the patients who used OCS before beginning biologics had four or more OCS prescription claims, and 11% had chronic OCS use. Specifically, 39% of those with chronic OCS use had suboptimal adherence with a mean PDC of less than 80%, 35% with a mean PDC of less than 70%, 26% with a mean PDC of less than 60% and 17% with a mean PDC of less than 50%.

Among the patients with chronic OCS use who were at GINA step 4 or 5, 32% had a mean PDC of less than 80%, 32% had a mean PDC of less than 70%, 20% had a mean PDC of less than 60%, and 9% had a mean PDC of less than 50%.

Conclusions, next steps

Advancing patients to biologic therapy before evaluating treatment adherence is contrary to guidelines, the researchers wrote, as patients with suboptimal adherence could benefit from improved adherence without escalation.

“The results of this study build upon the prior research noted and reinforce the need to better oversee that the appropriate patient is begun on a biologic,” Oppenheimer said. “They are not a reward for nonadherence.”

With biologics, the researchers wrote, average annual costs for care increase from $14,071 to $34,887. Even then, the researchers continued, many patients on biologic therapy still experience severe, uncontrolled asthma. These costs can impact the population health level of care as well, due to the high prevalence of asthma.

“The system needs to do a better job of ensuring adherence, appropriate phenotype and true need (exacerbation criteria) before beginning biologic agents,” Oppenheimer said.

By objectively monitoring patient adherence to maintenance medication via electronic monitoring systems and other means, clinicians may be able to achieve asthma control more effectively and more cost-effectively, according to the researchers.

“As doctors, we are driven to make our patients feel better. We need to push to improve the system,” Oppenheimer said.

“Insurers and pharmacy benefit management need to engage physicians in aiding to improve the system. This could include working to reduce the price of controller therapy and building models that track adherence in the standard care of asthmatic patients,” he continued.

Oppenheimer also said there was a need to continue to study the real-world use of asthma medicines, determine where impediments occur (such as attention adherence) and study how to improve adherence — for example, reducing costs of medicine and/or insurance premiums to reward adherence.

“We are beginning to acknowledge the problems,” he said. “Now we need to figure out how to fix them.”

References:

• Barnes, PJ. Chest. 2017;doi:10.1016/j.chest.2016.09.023.
• Jeffery MM, et al. J Allergy Clin Immunol Pract. 2021;doi:10.1016/j.jaip.2021.02.031.
• Ledford D, et al. J Allergy Clin Immunol. 2016;doi:10.1016/j.haci.2016.08.054.

For more information:

John Oppenheimer, MD, can be reached at nallopp22@gmail.com.