Factors Associated With Switching Biologic Therapies in Severe Asthma

Multiple asthma inhalers
Multiple asthma inhalers
What are the clinical characteristics of patients with severe asthma who switch biologic therapies, and what other factors are associated with switching?

Patients taking biologics for severe asthma who switch biologic therapies share certain characteristics, including high blood eosinophil counts, younger age, and aspirin-exacerbated respiratory diseases (AERD). These were among research findings recently published in the Journal of Asthma and Allergy.

Researchers in Japan sought to pinpoint patient characteristics and factors associated with switching biologics because no established guidelines exist for the selection, switching, or discontinuation of biologics, despite the increased use of such therapies among those with severe asthma.

The retrospective study of 42 patients with severe asthma treated with biologics was conducted at the Hokkaido University Hospital, Sapporo, Japan between June 23, 2016 and April 30, 2021. The investigators compared the characteristics of patients who continued taking a certain biologic treatment with those who switched. The time to switch biologics was evaluated by type 2 inflammatory biomarkers, pulmonary function indices, and scores on the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC, a diagnostic scoring tool using findings of sinus computed tomography and blood tests, in which eosinophilic chronic rhinosinusistis is determined by a score of 11 or more). Researchers also assessed the existence of comorbidities, including AERD, using the Kaplan-Meier method and a multivariate Cox proportional hazards model.

Because the study concentrated on switching biologics, individuals who discontinued omalizumab before the introduction of an alternative biologic (mepolizumab) on June 23, 2016, were excluded. The diagnosis of severe asthma was based on the European Respiratory Society/American Thoracic Society guidelines for adult asthma. Patients were divided into 2 groups: patients treated effectively with first-line biologic therapy during the observational period (continuous group) and those who needed to switch the initial biologic drug (switched group).

Among the 31% of patients (13 of 42) who switched biologics, 8 were given mepolizumab, and 5 were given benralizumab at baseline. The study showed that participants who required switching typically had high blood eosinophil counts, younger age, eosinophilic chronic rhinosinusitis, and AERD.

The length of time before switching biologics was significantly shorter in the subgroups of patients with eosinophilic chronic rhinosinusitis or AERD, compared with their counterparts (both, P < .05). Multivariate analysis showed that JESREC scores of 11 and higher as well as younger age were independently associated factors for switching biologics. Forced expiratory volume in 1 second (FEV1) percent predicted and the FEV1/forced vital capacity ratio were not significantly different between the 2 groups.

The authors conceded certain limitations. Because the study was retrospective, no clear criteria existed for stopping or switching the therapy, so the decision whether to discontinue or switch biologics depended on the attending physician. The sample size was comparatively small, which could have affected the results. Before entry to the study, 3 patients had been treated by other biologics, which also could have influenced the findings. The indications and clinical availabilities of the 4 biologics involved — dupilumab, mepolizumab, benralizumab, and omalizumab — varied in Japan and also may have impacted the results.

The researchers concluded that a multidimensional approach to the use of biologics, which includes the assessment of comorbidities, would enhance the management of severe asthma, especially when using anti-interleukin-5 agents. ”The selection and switching of biologics should be considered holistically and not just based on the organ system,” the authors recommend.

Disclosure: Multiple authors declared affiliations with the pharmaceutical and biopharmaceutical industries. Please refer to the original article for a full list of disclosures.


Matsumoto-Sasaki M, Simizu K, Suzuki M, et al. Clinical characteristics of patients and factors associated with switching biologics in asthma. J Asthma Allergy. Published online February 9, 2022. doi:10.2147/JAA.S348513