In a study presented at ATS 2020, investigators test 3 different dosing regimens of tezepelumab in asthma patients with both high and low levels of IL-5 and IL-13.
Tezepelumab could help patients with moderate and severe asthma avoid additional exacerbations.
In data planned for presentation at the American Thoracic Society (ATS) 2020 International Conference, a team, led by Jonathan Corren, MD, David Geffen School of Medicine, UCLA, evaluated the effect of tezepelumab treatment on annualized asthma exacerbation rates according to baseline levels of serum interleukin-5 (IL-5) and IL-13.
Tezepelumab is a human monoclonal antibody that blocks the activity of thymic stromal lymphopoietin, an epithelial cytokine implicated in asthma pathogenesis.
For the asthma inflammatory response, IL-5 and IL-13 are commonly linked to increased levels of eosinophils and fractional exhaled nitric oxide (FeNO), respectively.
In the phase 2b trial, dubbed the PATHWAY study, the investigators also assessed the correlation between IL-5 and IL-13 with conventional type-2 biomarkers in 550 patients.
The investigators examined patients with severe, uncontrolled asthma between 18-75 years old. Each patient was randomized to receive either subcutaneous tezepelumab (70 mg every 4 weeks [n = 138] , 210 mg every 4 weeks [n = 137], 280 mg every 2 weeks [n = 137]) or a placebo (n = 138) for a total of 52 weeks.
The baseline characteristics of the 4 groups were generally similar between patients with high (n = 114) and low (n = 115) levels of IL-5 and IL-13.
However, baseline blood eosinophil counts, FeNO, and total serum immunoglobulin (Ig)E levels were higher across the different treatment groups in patients with high levels of IL-5 and IL-13 when compared to low levels (560 vs 160 cells/µL; 38 vs 15 ppb; 193 vs 111 IU/mL, respectively). This was also true for the use of maintenance oral corticosteroids (mOCS, 9.7% vs 5.1%) and the proportion of patients with nasal polyps (25.0% vs 6.4%).
The researchers evaluated serum IL-5 and IL-13 levels using a sandwich immunoassay and determined annualized asthma exacerbation rates in patients with high (both ≥ median) and low (both < median) IL-5 and IL-13 levels at baseline.
The team presented data for pooled tezepelumab doses, excluding the 70 mg group, where they did not measure IL-5.
Over the 52 week study, the AAER in the placebo group was ultimately higher in patients with high levels of IL-5 and IL-13 when compared to low levels (1.09 vs. 0.92). When compared to placebo, the AAER in the pooled tezepelumab group decreased by 74% (95% CI, 47-87) in the high level group and 81% (95% CI, 58-91) in the low level IL-5 and IL-13 group.
Overall, the study drug significantly reduced annualized asthma exacerbation rates by up to 71% when compared to placebo in adults with severe, uncontrolled asthma.
“Among patients with severe, uncontrolled asthma, high IL-5 and IL-13 levels were associated with increased T2 biomarkers (blood eosinophils, FeNO, total IgE), mOCS use and nasal polyps,” the authors wrote. “Tezepelumab treatment resulted in similar reductions in AAER in patients with high and low baseline levels of IL-5 and IL-13, providing further evidence that tezepelumab can meaningfully reduce exacerbations in a broad population of patients with severe asthma.”
The study, “The Effect of Tezepelumab on Exacerbations in Patients with Severe, Uncontrolled Asthma According to Baseline Serum IL-5 and IL-13 Levels: Results from the Phase 2b PATHWAY Study,” was published online by ATS 2020.