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Pre-treatment disease trajectories in severe asthma impact treatment-related outcomes, according to a study by Johannes Martin Schmid, PhD, and colleagues.
Although only 4% to 8% of patients with asthma have severe disease, the burden is significant.
“This heterogeneous subpopulation is characterized by severe daily symptoms, intensive pharmacotherapy, and frequent exacerbations leading to loss of lung function, corticosteroid exposure-associated comorbidities, and impaired [QOL],” researchers wrote in the European Respiratory Journal.
The advent of more effective therapies has reduced disease and treatment burdens for many patients and achieved clinical remission for some, but little is known about the long-term disease trajectories prior to the start of biologic treatment.
Johannes Martin Schmid, PhD, and colleagues identified patients who started biologic therapy between 2016-2022. They conducted a sequencing analysis for the intensity of inhaled corticosteroid treatment over time and a cluster analysis for “unsupervised” disease trajectories before starting biologics.
Pre-Treatment Disease Trajectories in Severe Asthma
The study included 755 patients. The researchers reported that cluster analysis revealed three main pre-biologic disease trajectories: chronic severe asthma (26% of the cohort), gradual-onset severe asthma (35%), and recent sudden-onset severe asthma (39%).
A long duration of disease and intensive inhaled steroid therapy characterized the chronic severe cluster. More than half of these patients were in active treatment for 23 years before starting biologic therapy, and the same percentage had used high-dose or supratherapeutic inhaled corticosteroids 20 years before starting biologic therapy. Patients in the chronic severe asthma cluster were slightly older than those in the recent, sudden onset severe asthma cluster (median age, 59 vs 55). They were also more likely to be women (58% vs 45%) and the least likely of any cluster to be part of the workforce.
In the gradual, severe onset cluster, patients tended to have longer histories of treatment with inhaled corticosteroids that intensified with time. About half of the patients in this cluster had escalated to a high-dose or supratherapeutic inhaled corticosteroid 2 years before initiating biologics. This group represented an intermediate level of impairment between the other two groups, the researchers wrote.
Patients in the recent sudden onset cluster experienced a rapid onset of asthma and quickly escalated to high-dose inhaled steroids. Less than half of patients with recent, sudden onset severe asthma had taken any inhaled therapy 3 years before starting a biologic, and just 10% of patients in this cluster had taken an inhaled medication 10 years before biologic therapy. Patients in this cluster were more commonly former smokers (54%) compared with the chronic cluster (39%) and smoked more over time, with a median of 17 pack-years (range, 8-27) compared with the chronic cluster’s median of 8 pack-years (range, 4-15).
Efficacy of Treatment Across Asthma Clusters
All clusters had similar clinical response rates, Dr. Schmid and colleagues reported. However, the recent, sudden onset cluster had the highest remission rate (32%), whereas the chronic cluster had the lowest remission rate (17%). The researchers noted that the chronic cluster had a significantly lower prevalence of normalized lung function than the recent sudden cluster, with 32% of patients with a FEV1%pred ≥ 80% versus 56% for those in the recent sudden onset cluster (P<0.001).
The chronic onset cluster had the highest prevalence rate of “too late” asthma, at 56%, according to the researchers. According to Dr. Schmid and colleagues, the too-late form of asthma involves permanent lung damage and often irreversible adverse effects due to corticosteroid exposure. The recent sudden-onset cluster had the lowest prevalence, at 39%.
Patients in the recent sudden onset cluster were significantly less likely to have too late asthma compared with the chronic cluster (median odds ratio [OR], 0.82; range, 0.74-0.9 versus 0.9 (range, 0.82-0.998), P=0.045). However, there were no significant differences in the odds of too late asthma between the chronic and gradual onset groups.
Drivers of Disease & Comorbidity Burden
The researchers noted that the study was limited by its “highly selected population” and the fact that patients’ requirement to be treated for at least a full year may have furthered selection bias. The study also did not explore biological mechanisms or causality of the relationships reported.
However, the study successfully identified three distinct disease trajectories preceding initiation of biologic therapy for severe asthma.
“Our data suggest that disease and comorbidity burden is driven by a product of disease duration and activity, indicating that timely intervention is key to reducing the burden associated with severe asthma,” Dr. Schmid and colleagues wrote.
