Tezepelumab in near-fatal asthma requiring VV-ECMO

Phase III studies have demonstrated that the anti-TSLP biologic tezepelumab significantly reduces asthma exacerbations in severe asthma, regardless of endotype. However, evidence on its use in near-fatal asthma is lacking. Tezepelumab's ability to reduce bronchial hyperresponsiveness and ILC2, eosinophil, and mast cell activation may contribute to attenuating severe exacerbations. We report the case of a 44-year-old female active smoker (25 pack-years) with a six-month history of asthma, admitted to the ICU with near-fatal asthma triggered by influenza A infection. Orotracheal intubation and invasive ventilation were required. Due to persistent ventilatory failure and acidaemia despite high-pressure ventilation, VV-ECMO was initiated. Treatment included oseltamivir, high-dose intravenous steroids, magnesium, and salbutamol. Attempts to reduce sedation repeatedly induced severe bronchospasm. After five days on VV-ECMO, given the critical condition and lack of asthma endotype data, azithromycin 250 mg every other day and tezepelumab 210 mg were administered to achieve a potent anti-inflammatory effect. Within 48 hours of tezepelumab administration, progressive weaning from VV-ECMO and ventilation was possible, leading to successful extubation. The patient was transferred to the pulmonology unit for rehabilitation. Forced oscillation techniques revealed reduced reactance and increased resistance at 5 Hz, both improving one month post-discharge. This is the second reported case of near-fatal asthma requiring VV-ECMO treated with tezepelumab, and the first in a patient without prior asthma diagnosis. Biologic therapy in acute settings may improve outcomes in refractory near-fatal asthma, warranting further clinical investigation.