Starting, switching biologics reduces exacerbations among patients with severe asthma
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Patients who began taking or who switched biologics for severe asthma consistently experienced meaningfully reduced exacerbations, according to a real-world analysis published in Annals of Allergy, Asthma & Immunology.
As a result, individual approaches to treatment could improve outcomes, the researchers continued.
“This study was an analysis of the ongoing CHRONICLE study, a prospective, real-world, noninterventional study of U.S. adult patients with confirmed severe asthma (SA) treated by allergists/immunologists or pulmonologists,” Chris Ambrose, MD, MBA, franchise head of U.S. medical and respiratory at AstraZeneca, told Healio.
“The objective of this analysis was to examine real-world biologic use and associated outcomes among adults receiving biologics, with the overall goal of adding to what is known about the use of biologics to treat severe asthma,” Ambrose said.
Use of biologics
The researchers analyzed data from 2,793 patients (mean age, 54.2 years; 68.8% women; 74.6% white; 52.9% treated by a pulmonologist) enrolled in the CHRONICLE study between February 2018 and February 2021.
Among the 2,025 patients reporting any biologic use — with 89% of these patients having ongoing use at follow-up — 47% had used omalizumab (Xolair; Genentech, Novartis), 27% had used benralizumab (Fasenra, AstraZeneca), 26% had used mepolizumab (Nucala, GlaxoSmithKline), 18% had used dupilumab (Dupixent, Sanofi Genzyme/Regeneron) and 3% had used reslizumab (Cinqair, Teva Respiratory).
“Among specialist-treated patients with severe uncontrolled asthma, we observed significant use of biologics, as 66% of eligible patients received them. Among those receiving biologics, 89% continued receiving them as of our last data collection,” Ambrose said.
As these biologics were approved for use, their distribution in treatment changed substantially, the researchers found. For example, benralizumab was the most frequently initiated treatment at 39% between November 2017 and October 2018. But from October 2018 to February 2021, dupilumab was most frequently initiated at 34%.
Switching, stopping biologics
During the study period, 324 (16%) of the patients receiving biologics reported switching to another biologic 404 times after a median duration of treatment with the first biologic of 309 days (interquartile range [IQR], 119-674 days). Dupilumab had the shortest median duration of treatment at 157 days, whereas omalizumab had the longest at 670 days.
Before October 2018, benralizumab was the most common biologic to which patients switched, but after October 2018, it was dupilumab. Of the patients who switched, 26% did so because their asthma symptoms had gotten worse and 20% did so because the biologic’s effectiveness had waned over time.
Also, 253 patients (12.5% of biologic recipients) reported stopping biologic treatment 258 times. These patients stopped treatment because their asthma symptoms had gotten worse (13%), the treatment was not effective (6%) or because the costs were too expensive or not covered by insurance (2%).
Overall, a greater proportion of patients who switched or stopped using biologics had used maintenance systemic corticosteroids in the previous 12 months, were younger at enrollment, were employed full-time and had commercial insurance compared with those who did not switch or stop using biologics.
Efficacy
Exacerbations fell by 58% from 1.8 to 0.76 per patient-year among patients who began biologic treatment. Patients who started biologics targeting IL-5 (mepolizumab and reslizumab), the IL-5 alpha receptor (benralizumab) and the IL-4 alpha receptor (dupilumab) experienced the greatest reductions, the researchers found.
Also, Ambrose said, reductions in asthma exacerbations were higher among the 62% of patients who used non-anti-IgE biologics compared with the 44% of patients using anti-IgE biologics.
Comparing results 6 months before and after biologic initiation, patients with prebiologic FEV1 of less than 80% experienced a 66% reduction in exacerbations, and patients with FEV1 totals of 80% or greater experienced a 53% reduction in exacerbations.
Similarly, patients who were never smokers experienced a 63% reduction, former smokers experienced a 50% reduction, patients with COPD experienced a 58% reduction, and those with no COPD experienced a 52% reduction in exacerbations.
When the analysis looked at patients with data for 12 months before and after biologic initiation, results were similar with exacerbation rates falling by 70% from 1.72 to 0.5 per patient-year.
Also, among these patients, those who switched biologics experienced a 49% reduction in exacerbations from 1.47 to 0.75 per person-year. Those who switched from anti-IgE therapy to therapy targeting IL-5, IL-5 alpha receptors and IL-4 alpha receptors saw greater reductions than those who switched among the therapies targeting IL-5, IL-5 alpha receptors and IL-4 alpha receptors, the researchers found.
Noting the consistent associations between switching biologic treatment and reductions in exacerbations, the researchers said that adapting biologic selection based on patient responses offers benefits and highlights the need for personalized approaches to therapy.
“For asthma specialists, our findings support current use of biologics and support further consideration of biologic use among patients with severe uncontrolled asthma who are not receiving them,” Ambrose said.
“For primary care physicians, these findings highlight the benefits of referring patients with severe asthma to specialists for assessment and/or co-management, which is recommended by national guidelines,” he continued.
Despite these recommendations, Ambrose added, recent research has suggested that fewer than 40% of patients with SA receive specialist care.
“CHRONICLE is an ongoing study, and many further analyses are planned as additional data is acquired and the treatment of severe asthma continues to evolve with the approval of new biologics and other novel treatment approaches,” Ambrose said.
For more information:
Chris Ambrose, MD, MBA, can be reached at chris.ambrose@astrazeneca.com.
Perspective
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The CHRONICLE study by Panettieri and colleagues is a real-world, noninterventional study reporting treatment outcomes of patients with SA. Almost 3,000 patients with SA were included in the study, with nearly 90% being treated with biologics. Approximately 16% also switched biologics during the study period. Specialists used a wide variety of biologics, and preferences changed over time as more biologics became FDA-approved. Most of the patients on biologics experienced a clinically meaningful decrease in asthma exacerbations.
The findings of the CHRONICLE study are in line with my own experience and the experience of others treating patients with SA. As shown in the study, the availability of FDA-approved biologics has significantly improved the management of patients with SA, most notably by decreasing asthma exacerbations.
That said, questions remain on how to best choose a biologic for an individual patient, because many patients meet criteria for treatment with several if not all of the six FDA-approved options. In addition, a significant number of patients eventually switches biologics due to a suboptimal clinical response.
Future research needs to focus on how to more precisely identify the ideal patient for each biologic option in hopes of improving clinical outcomes and decreasing therapeutic failures for patients with SA. The CHRONICLE study also illustrates that patients with SA should be managed by clinicians familiar with FDA-approved biologics because these medications have proven efficacy in this high-risk population.
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