Patients with severe asthma who were new to omalizumab showed significant clinical improvement after 2 weeks of treatment, according to data from a pilot study of 26 adults.
Although omalizumab is approved for severe allergic asthma, not all patients respond well, and are considered nonresponders in the absence of clinical benefits within 16 weeks of starting treatment, wrote Todor A. Popov, MD, of the University Hospital St. Ivan Rilski, Sofia, Bulgaria, and colleagues.
“Since airway inflammation is a cardinal feature of asthma, we reasoned that early changes in its level may determine the subsequent course of the disease,” they said.
In a study published in Annals of Allergy, Asthma & Immunology, the researchers recruited 26 adults with severe asthma who were new to biologic therapy and eligible for omalizumab. The patients ranged in age from 22 to 70 years, and 13 were men. Patients received omalizumab doses between 150 mg and 375 mg every 2-4 weeks based on body weight and pretreatment serum IgE levels, and they were assessed at baseline and followed for a total of 18 weeks (2-week run-in and 16 weeks of treatment).
Patients rated their overall discomfort from asthma on a 100-mm visual analogue scale (VAS). Asthma control was assessed via the asthma control questionnaire (ACQ), and disease-related quality of life was assessed via the Asthma Quality of Life Questionnaires (AQLQ). All patients reported significant improvement across all three measures after 2 weeks and through the study period after the first administration of omalizumab at week 0 (P < .001).
Clinical response was based on quantitative indicators of airway and systemic eosinophilic inflammation: fractional exhaled nitric oxide (FeNO), eosinophil cationic peptide (ECP), and the temperature of the exhaled air (EBT, exhaled breath temperature). The researchers also measured fractional EBT (FrEBT) by measuring the EBT of central and peripheral airways at the beginning and end of the expiration.
Overall, EBT decreased significantly after 2 weeks, and the decrease lasted until week 16. FrEBT decreased significantly after 4 weeks. ECP reached statistical significance at week 16 (P = .029). FeNO showed a downward trend, but the decrease did not reach statistical significance, the researchers wrote.
These results might suggest that “after blocking IgE, the eosinophilic inflammation is not suppressed well and fast enough,” the researchers noted. “Consequently, indicators of eosinophilic inflammation may not be suited for early predictors of success of omalizumab treatment,” they added. The drop in EBT after the first dose of omalizumab may predict effectiveness for a particular patient, while the FrEBT results “may mean that it takes longer to suppress the inflammatory process in the vast basin of the small airways,” they noted.
A key limitation of the findings was the small sample size, although the study was designed as a proof-of-concept on which to base sample size calculation for larger trials with EBT as a predictive marker, the researchers said.
However, the EBT and FrEBT signals reached statistical significance, and the results warrant confirmation in larger trials; such confirmation may spare patients from expensive and ineffective treatments, they concluded.
The study was funded by Novartis. The researchers had no financial conflicts to disclose.