D1.109 - Predominance of eosinophilic pathogenetic mechanisms in a severe allergic asthma patient on biologic therapy

Despite biologic therapy, a significant proportion of severe asthma patients remain uncontrolled and/or require long term oral corticosteroids (OCS). Currently there is no clear guidance on how and when to switch between available biologic agents and only few data was published on the combination of two different biologics. We present the case of a 39-year-old male patient, former smoker, with a history of child-onset allergic asthma and chronic rhinosinusitis, with multiple sensitizations to pollens (grass, cereals), house dust mite and mold. Around the age of 30 years his asthma was categorized as severe. During phenotyping, he presented T2-high inflammation with total IgE=1379 IU/mL, blood eosinophils=846 cells/µL. In 2017 biologic therapy with omalizumab was initiated and continued for approximately 1.5 years. In March 2019 omalizumab was stopped due to lack of efficacy. He was administering fluticasone/salmeterol 500/50mcg BID, montelukast 10mg OD, levocetirizine 5mg OD and mometasone 50mcg BID intranasally, however his asthma was not controlled (ACT=16), and he received maintenance OCS. Spirometry showed severe obstructive dysfunction (FEV1=31%), total IgE=358.3IU/mL and blood eosinophils up to 370 cells/µL. Chest imaging was normal. In June 2020, patient was started on benralizumab with good symptoms control (ACT>20), improved lung function (FEV1 up to 63%) and no exacerbations, which allowed withdrawal of OCS. During the following 4 years we noticed a decline in lung function, asthma and rhinosinusitis symptoms were partially controlled, he presented an exacerbation requiring OCS in 2023, and FeNO was 131ppb in February 2024. In June 2024 the biologic therapy was switched from benralizumab to dupilumab. Surprisingly, we noticed a deterioration of asthma control, reoccurrence of exacerbations, a decrease in lung function, need for OCS and a significant rise in blood eosinophils up to 3000 cells/µL, which prompted reinitiation of benralizumab (anti-TSLP not available). The symptoms control was again achieved, with no further exacerbations or need for OCS, however the lung function remained poor. Biologic therapy in severe asthma is highly effective in selected, carefully phenotyped cases, however a single biologic agent may not be able to address all inflammatory pathways in some patients, which may explain failure to achieve clinical remission.