Factors Linked to Switching Biologic Treatments in Patients with Severe Asthma

Higher blood eosinophils, younger age, and eosinophilic chronic rhinosinusitis were among factors associated with a switch from initial biologic therapy in a new study.

Patients with severe asthma who switch between biologic therapies may be more likely to have higher blood eosinophil (Eos) counts, be of younger age, have eosinophilic chronic rhinosinusitis (ECRS) and aspirin exacerbated respiratory disease (AERD),

The findings come from a Japanese retrospective cohort study newly published in the Journal of Asthma and Allergy.

Biologics play a significant role in the treatment of severe asthma, write researchers led by Machiko Matsumoto-Sasaki, from the Department of Respiratory Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan. However, the 4 agents approved for treatment of hard to control asthma (dupilumab, mepolizumab, benralizumab, and omalizumab) have overlapping indications which "leaves the ultimate decision at the discretion of the treating physician, thus some patients have to discontinue," requiring more time to optimize treatment. Moreover, they emphasize, there are currently no established clinical guidelines for initial biologic therapy selection, switching among agents, or discontinuation.

According to the researchers, the goal of their study was to identify clinical characteristics of patients with severe asthma who required switching biologic agents and additional factors associated with switching. The retrospective cohort study compared the characteristics between participants who did/did not switch and examined clinical factors associated with the amount of time to a biologic switch.

To create the study cohort, Matsumoto-Sasaki et al retrospectively reviewed medical records of patients with severe asthma treated with biologics at the Hokkaido University Hospital between March 1, 2009, when omalizumab was introduced, and April 30th, 2021. Analysis was conducted between June 23, 2016, when mepolizumab became available in Japan, and the April 2021 date. Investigators used criteria from the European Respiratory Society/American Thoracic Society guidelines to determine a diagnosis of severe asthma.

The time during which a switch between biologics was observed began on 1) June 23, 2016, for participants who received omalizumab before that date and 2) the date of starting a biologic for participants prescribed a biologic on/after the June 2016 date.

The chart review identified 45 patients who had initiated biologics including 3, subsequently excluded, who had discontinued omalizumab before the launch of mepolizumab.

For the analysis, patients were divided into 2 groups: those who were treated successfully with first-line biologic therapy during the observation period (continuous group) and those who required switching the initial biologic drug (switched group).

Charactertistics linked to switching

Among the 31% of patients (13 of 42) who switched biologics, 8 were given mepolizumab, and 5 were given benralizumab at baseline, the study found. Those who required switching biologics were significantly younger at baseline than those in the continuous group (mean age 51 years and 64 years, respectively) and also were significantly younger at age of asthma onset (mean age 32 years vs 43 years). Switched group patients also had blood Eos counts significantly higher (706 cells/µL) than those whose treatment was continuous (298 cells/µL). However, the investigators found no significant differences between the groups in measures of FEV1 % predicted and FEV1/FVC.

Among reasons for switching biologic agents, 8 patients reported symptoms of “uncontrolled asthma,” and some required additional oral or systemic corticosteroids or unscheduled hospital visits.

Comorbidities. Both AERD and ECRS were more common among those in the switched group with elevated JESREC scores (≥11) in 61.5% of those who switched vs 27.6% of those in the continuous group. Nasal polyps and olfactory cleft lesions also were more prevalent in the switched vs continuous group.

Shorter time to switch

When the investigators examined time to switch biologics, they found the average number of days was 975, a period that was shorter among those with JESREC scores of ≥11 than in the group with JESREC scores of <11 (1053 days vs 1480 days; P<.05) (see sidebar).

Time to switching biologic agents was also significantly shorter for patients with vs without AERD (750 days vs 1346 days; P<.05). In multivariate analysis, JESREC ≥11 and younger age were independently associated with the time to switch biologics, but presence of AERD and FEV1 % predicted were not.

Study limitations cited by the authors include the retrospective design and comparatively small sample sized. Also, clinical availability of the 4 biologics was variable in Japan and may have impacted findings.

The authors conclude that “a multidimensional approach when using biologics, including the evaluation of comorbidities, would improve the management of severe asthma, especially with anti-IL-5 agents.” Switching, they assert, “should be considered holistically and not just based on the organ system.”

Reference: 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