Pulmonology Xagena

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Severe, uncontrolled asthma with and without nasal polyposis: efficacy of Tezepelumab - A post hoc analysis of the phase 2b PATHWAY study

Tezepelumab is a human monoclonal antibody that blocks thymic stromal lymphopoietin ( TSLP ), an epithelial cytokine implicated in asthma pathogenesis, from binding to its heterodimeric receptor.
In the phase 2b PATHWAY study, Tezepelumab has significantly reduced annualized asthma exacerbation rates ( AAERs ) versus placebo, irrespective of baseline disease characteristics, and improved lung function and symptom control, in adults with severe, uncontrolled asthma.

This post hoc analysis has assessed the efficacy of Tezepelumab in adults with severe, uncontrolled asthma with and without nasal polyposis ( NP ).
In the PATHWAY study, participants ( n=550 ) were randomized 1:1:1:1 to receive subcutaneous Tezepelumab 70 mg every 4 weeks ( Q4W ), 210 mg Q4W or 280 mg every 2 weeks ( Q2W ), or placebo Q2W, for 52 weeks.

The AAER over 52 weeks and the change from baseline to week 52 in blood eosinophil count, fractional exhaled nitric oxide ( FeNO ) levels and serum levels of interleukin ( IL )-5 and IL-13 with Tezepelumab 210 mg ( phase 3 dose ) and placebo were analyzed in patients grouped by self-reported presence ( NP+ ) or absence ( NP- ) of nasal polyposis at screening.

At baseline, NP+ patients had higher blood eosinophil counts, higher FeNO levels and higher serum IL-5 and IL-13 levels than NP- patients.

Tezepelumab 210 mg has reduced the AAER versus placebo to a similar extent in both NP+ and NP- patients ( NP+, 75% [ 95% confidence interval ( CI ): 15, 93 ], n=23; NP-, 73% [ 95% CI: 47, 86 ], n=112 ).

Patients treated with Tezepelumab 210 mg have demonstrated greater reductions in blood eosinophil count and levels of FeNO, IL-5 and IL-13 than placebo-treated patients, irrespective of NP status.

In conclusion, Tezepelumab has reduced exacerbations and reduced type 2 inflammatory biomarkers in patients with and those without nasal polyposis, supporting its efficacy in a broad population of patients with severe asthma. ( Xagena )

Emson C et al, J Asthma Allergy 2021;14: 91-99