Low T2 Asthma: What Anti-TSLP Data Show in Low-Eosinophil Patients

This episode, "Low T2 Asthma: What Anti-TSLP Data Show in Low-Eosinophil Patients," features Dr. Wechsler testing a widely held assumption against the data.

Dr. Chupp raises low T2 asthma, describing patients with low biomarkers who may be neutrophilic or polygranulocytic depending on the defining study. The prevailing view is that anti-TSLP therapies work better in these patients than the high T2 biologics. He asks Dr. Wechsler why.

Dr. Wechsler's answer complicates the premise. He says the field is still learning TSLP biology and does not have good data on anti-TSLP in broad non-type 2 patients. The drug works well in low-eosinophil patients in asthma, he notes, but low eosinophils are not the same as non-type 2. A patient can have low eosinophils alongside high nitric oxide, or an allergic phenotype. Data in pure non-type 2 asthma are still awaited.

He then walks the evidence. Anti-TSLP performed well in low-eosinophil asthma, with a 39% reduction in exacerbations. In the COPD trial, however, there was minimal effect in the low-eosinophil group. In the more recent SUNRISE study of oral steroid-dependent patients randomized against placebo, the drug reduced both steroid dose and exacerbations, but that finding sat primarily in patients with background eosinophilia. A study of a TSLP receptor-targeted agent in a broad asthma population showed the same pattern: major efficacy in patients with elevated eosinophils, no significant exacerbation reduction in the low-eosinophil group, though lung function did improve in those patients.

His conclusion is that much remains unknown about the exact role of TSLP and epithelial cytokines in non-type 2 asthma. He points to where the answer may come from: TSLP has receptors on airway smooth muscle and on mast cells, and studying where TSLP binds may explain the pattern. Dr. Chupp adds that anti-IL-33 therapies are in development with some successful clinical data.

Up next, in "The Unified Airway: Linking Severe Asthma and Sinus Disease," the experts move above the lungs.