A 52-week assessment shows patients of varying interleukin serum levels equally benefitted from the TSLP inhibitor.
Jonathan Corren, MD
Tezepelumab’s benefit for asthma exacerbation reduction may be more robust than previously thought.
New findings from an assessment of the investigative monoclonal antibody showed treated patients with severe, uncontrolled asthma had similar reductions in annualized asthma exacerbation rates (AAER) regardless of baseline serum interleukin 5 and 13 (IL-5; IL-13) levels.
As IL-5 and IL-13 have been linked to increased eosinophil and fractional exhaled nitric oxide (FeNO) levels in patients with asthma, investigators believe these findings indicate the biologic can improve asthma symptoms regardless of type 2 inflammation presence.
In the new data planned for presentation at the American Thoracic Society (ATS) 2020 International Conference this year, a team of investigators led by Los Angeles-based allergist Jonathan Corren, MD, assessed the TSLP inhibitor candidate tezepelumab in patients with severe, uncontrolled asthma.
Corren and colleagues sought to understand the effect of the subcutaneous therapy on AAER based on patient baseline levels of serum IL-5 and IL-13—as well those levels’ correlation with conventional type 2 inflammation biomarkers.
The team randomized 550 patients aged 18-75 years old to either placebo (n = 138), tezepelumab 70 mg (n = 138) or 280 mg (n = 137).
Baseline characteristics were generally similar among patients with either high or low IL-5 and IL-15 levels. However, investigators noted baseline blood eosinophil counts (560 cells/uL vs 160), FeNO (38 ppb vs 15), and total serum immunoglobulin E (IgE) levels (193 IU/mL vs 111) were greater among treatment groups in patients with high IL-5 and IL-13 levels, versus those with low levels.
They also observed differences in maintenance oral corticosteroid use (9.7% vs 5.1%) and rate of patients with nasal polyps (25.0% vs 6.4%) in these same IL level groups.
At 52 weeks of treatment, investigators observed a greater AAER in patients with high IL-5 and IL-13 levels in the placebo group (1.09 vs 0.92). When compared to placebo, AAER in the pooled tezepelumab treatment group was reduced by 74% (95% CI, 47-87; P <.001) in the high IL level group, and by 81% (95% CI, 58-91; P <.001) in the low group.
AAER in the 210 mg tezepelumab group was reduced by 68% (P <.05) and 85% (P <.05) in the high- and low-level IL groups versus placebo, respectively.
Tezepelumab, from AstraZeneca and Amgen, was granted Breakthrough Therapy Designation by the US Food and Drug Administration (FDA) for its potential to treat patients with severe asthma in 2018.
Corren discussed the potential of the TSLP inhibitor with HCPLive® in a DocTalk podcast last month, when he detailed the significance of the tezepelumab’s mechanism of action in patients with asthma.
“Because the drug may have very profound effects in modifying the type 2 inflammatory response, we’ll have to examine the possibility that you can give it for shorter periods of time,” he explained. “But that’s not well established.”
In these newest findings, Corren and colleagues concluded observed associations between high IL-5 and IL-13 levels, increased type 2 inflammation biomarkers, maintenance oral corticosteroid use, and nasal polyps among adults with severe asthma. They also observed indiscriminate benefit with tezepelumab in these patients.
“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,” they wrote.
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.