What Is New in Severe Asthma Research

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Christina E Ciaccio, MD, MSc

Christina E Ciaccio, MD, MSc
Assistant Professor of Pediatrics
University of Chicago Medicine
Comer Children’s Hospital
Chicago, Illinois, United States

Tezepelumab in Adults with Uncontrolled Asthma
Corren J, Parnes JR, Wang L, Mo M, Roseti S et al.
New England Journal of Medicine 2017; 377: 936-946  DOI:10.1056/NEJMoa1704064


An estimated 220 million people worldwide suffer from moderate to severe persistent asthma, many of whom remain uncontrolled despite maximal therapy with inhaled corticosteroids and long acting beta agonists. In this trial, tezepelumab, an anti-TSLP, was trialed as an adjunct therapy to combination therapy in those with uncontrolled asthma. This study was a multicenter, placebo-controlled, parallel-group, double-blind, phase 2 trial conducted at 108 sites across 12 countries and enrolled nonsmokers ages 18-75 with uncontrolled asthma despite treatment with a combination inhaler. Five hundred eighty-four patients were assigned to receive low (70mg every 4 weeks), medium (210mg every 4 weeks), or high (280mg every 2 weeks) dose tezepelumab subcutaneously or placebo. Tezepelumab reduced asthma exacerbation rates by 61% (primary end point). In addition, the time to first asthma exacerbation was longer in the tezepelumab groups compared to placebo, the risk of having an exacerbation was lower, and the change from baseline FEV1 was greater. Tezepelumab also resulted in a decrease in blood eosinophil, total IgE and forced exhaled nitric oxide. In general, tezepelumab was well tolerated with adverse reaction rates similar between groups and placebo. Serious events included stroke (2) and Guillain-Barre syndrome. The exciting results of this study highlight the potential of targeting upstream cytokines instead of the currently targeted downstream molecules in order to have a more broad effect on asthma. Although large phase 3 studies are needed to further exam efficacy and safety, tezepelumab offers a promising new therapeutic option for those with uncontrolled moderate to severe persistent asthma.

Last updated: Wednesday, November 22nd, 2017