Tezepelumab effective for severe uncontrolled asthma with, without perennial allergies

Tezepelumab reduced exacerbations, improved lung function and reduced biomarkers in patients with severe, uncontrolled asthma with or without perennial allergies, according to a post hoc analysis of the phase 2b PATHWAY study.

These results, published in The Journal of Allergy and Clinical Immunology: In Practice, suggest tezepelumab (Amgen, AstraZeneca) — a human monoclonal antibody IgG2 directed against thymic stromal lymphopoietin that attenuates asthmatic responses to allergen challenge in patients with mild asthma — also is efficacious in a broad population of patients with severe, uncontrolled asthma, according to the researchers.

Approximately 60% of patients with severe asthma have allergic asthma, Jonathan Corren, MD, an allergist-immunologist at David Geffen School of Medicine of UCLA, and colleagues wrote. When inhaled corticosteroids (ICS) can’t control moderate to severe allergic asthma, clinicians also may prescribe long-acting ₂ agonists (LABAs), such as omalizumab (Xolair; Genentech, Novartis).

The study included 550 current nonsmokers aged 18 years to 75 years with severe, uncontrolled asthma despite treatment with ICS and LABA who researchers randomly assigned to receive subcutaneous tezepelumab (70 mg every 4 weeks, n = 138; 280 mg every 4 weeks, n = 137; 280 mg every 2 weeks, n = 137) or placebo (n = 138) for 52 weeks.

As Healio previously reported, the study showed up to a 71% reduction in annualized asthma exacerbation rates (AAERs) with tezepelumab.

In the current post hoc analysis, Corren and colleagues sought to evaluate the efficacy of tezepelumab among patients with or without perennial allergies, defined by fluorescence enzyme immunoassay (FEIA) test. Researchers evaluated differences in AAERs between those two groups, as well as changes from baseline in forced expiratory volume in 1 second (FEV₁) and type 2 biomarkers.

Patients with sensitivities to perennial aeroallergens — including animal, dust mite and mold — comprised 46.2% of the study population. Patients with sensitivity to seasonal aeroallergens — including pollen of Bermuda grass, birch, common ragweed, Japanese cedar, Johnson grass and Timothy grass — comprised 38% of the study population.

Also, 33.7% of the participants had both perennial and seasonal aeroallergen sensitivities and 44% weren’t sensitive to either class.

Overall, 254 patients (mean age, 48.9 years; 59.8% women) were deemed FEIA positive and 261 (mean age, 54.3 years; 71.3% women) FEIA negative.

Tezepelumab treatment reduced AAERs among patients who were FEIA positive or negative for perennial aeroallergens compared with placebo.

Specifically, among patients who received the 210 mg dose, tezepelumab conferred a 78% (95% CI, 50-91) reduction in AAER among those FEIA positive for perennial aeroallergens and a 67% (95% CI, 27-85) reduction among those who were FEIA negative. The pooled tezepelumab dose groups demonstrated AAER reductions of 66% (95% CI, 40-81) among those who were FEIA positive and 71% (95% CI, 48-84) for FEIA-negative patients.

Regardless of perennial aeroallergen FEIA status, patients who received 210 mg of tezepelumab every 4 weeks saw decreases in blood eosinophil count and fractional exhaled nitric oxide, as well as improvements in pre-bronchodilator FEV₁, compared with placebo. The researchers observed these differences, which were sustained through week 52, as early as week 4.

Tezepelumab treatment also reduced total serum IgE in patients who were FEIA positive, with differences observed by week 4 and sustained until week 52, compared with placebo.

The researchers noted that the PATHWAY study was not prospectively powered to specifically investigate differences between patients with or without an allergic phenotype. Also, complete allergic status evaluations were not performed, and the study did not account for exposure to the relevant aeroallergens and their resulting symptoms.