Clinical Edge

Summaries of Must-Read Clinical Literature, Guidelines, and FDA Actions

Tezepelumab and Uncontrolled Asthma in Adults

N Engl J Med; ePub 2017 Sep 7; Corren, et al

Among patients treated for 52 weeks with long-acting beta-agonists and medium-to-high doses of inhaled glucocorticoids, those receiving tezepelumab had lower rates of clinically significant asthma exacerbations compared to those taking placebo, a recent study found. The randomized, double-blind, placebo-controlled trial compared subcutaneous tezepelumab at 3 dose levels with placebo over a 52-week treatment period. Researchers found:

  • The use of tezepelumab at a dose of 70 mg every 4 weeks (low dose; n=145 patients), 210 mg every 4 weeks (medium dose; n=145 patients), or 280 mg every 2 weeks (high dose; n=146 patients), resulted in annualized asthma exacerbation rates at week 52 of 0.26, 0.19, and 0.22, respectively, compared with 0.67 in the placebo group.
  • This resulted in exacerbation rates in the respective tezepelumab groups lower by 61%, 71%, and 66% compared to the placebo group.
  • Similar results were observed in patients regardless of blood eosinophil counts at enrollment.

Citation:

Corren J, Parnes JR, Wang L, et al. Tezepelumab in adults with uncontrolled asthma. N Engl J Med. 2017;377:936-946. doi:10.1056/NEJMoa1704064.

Commentary:

About 5% of patients with asthma have severe asthma that remains uncontrolled on high dose inhaled glucocorticoid therapy with long-acting beta agonists and new therapies are being developed for this cohort of patients. Patients with severe asthma fall into different phenotypes. There are those characterized by sputum eosinophilia, defined as 2% or more of leukocytes in a sample of sputum, accounting for about half of patients with severe asthma. Then there are patients with neutrophilic inflammation, with over 40% to 60% neutrophils in induced sputum samples. There are also patients with a mixed picture of inflammation. Currently available therapies for patients with severe asthma include anti-IgE therapy (Omalizumab), and anti–interleukin-5 monoclonal antibodies (Mepolizumab and Reslizumab, which are FDA approved, and Benralizumab which is currently being evaluated by the FDA). Also in development are interleukin-13 and interleukin-4 monoclonal antibody therapy. Tezepelumab is a human IgG2 monoclonal antibody that binds to thymic stromal lymphopoietin (TSLP), which is a cytokine produced in response to environmental and proinflammatory stimuli. It is an important potential mechanism because it works high up in the inflammatory cascade and in this study, appears to have a beneficial effect in patients across different asthma phenotypes. —Neil Skolnik, MD