Response to tezepelumab as a second-line biologic in a UK severe asthma population

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Background: Tezepelumab inhibits airway inflammation across multiple inflammatory pathways and is the most recently approved biologic for use in severe asthma. Objective: Characterize the response to tezepelumab in severe asthma patients who have not responded to or not tolerated a first-line biologic agent. Methods: Retrospective analysis of real-world patients completing 12 months of tezepelumab as a second-line biologic agent in a UK severe asthma service. Clinical response, defined by a 50% reduction in annualised asthma exacerbation rate (AER) and/or oral corticosteroid (OCS) dose, was evaluated at 4 and 12 months. Results: 25/118 patients on tezepelumab received the drug as a second-line agent after anti-IgE or anti-IL-5/R. 20/25 had a clinical response at 12 months. On treatment the AER decreased (6.48[±2.79] to 2.57[±2.87]). Clinical responders had a lower AER on treatment (1.80[±2.17]) vs. non-responders (7.67[± 1.15]); p=0.009. 28% were exacerbation-free. OCS dose decreased from 9.91[±8.65] mg to 6.45[±9.14] mg, with responders receiving a lower dose at 12 months (3.83[±3.74] mg) vs. non-responders (15.63[± 16.38] mg), p=0.021. ACQ6 score was lower in responders (1.68[±1.15]) vs. non-responders (4.92[± 0.83]); p=0.030. Predictors of response were a lower baseline ACQ score (p=0.009), perennial rhinitis (p=0.038), and lower FeNO (p=0.042). Responders had fewer exacerbations at 4 months (0.57[± 0.76]) vs. non-responders (4.50[± 0.71]); p<0.017. Conclusion: Most patients receiving tezepelumab as a second-line agent responded. Treatment was associated with improvements in exacerbations, OCS use and asthma control, but there remains a major unmet clinical need and further studies are required.