Association between pre-biologic T2-biomarker combinations and response to biologics in patients with severe asthma
Authors: Porsbjerg Celeste M. , Townend John , Bergeron Celine , Christoff George C. , Katsoulotos Gregory P. , Larenas-Linnemann Désirée , Tran Trung N. , Al-Lehebi Riyad , Bosnic-Anticevich Sinthia Z. , Busby John , Hew Mark , Kostikas Konstantinos , Papadopoulos Nikolaos G. , Pfeffer Paul E. , Popov Todor A. , Rhee Chin Kook , Sadatsafavi Mohsen , Tsai Ming-Ju , Ulrik Charlotte Suppli , Al-Ahmad Mona , Altraja Alan , Beastall Aaron , Bulathsinhala Lakmini , Carter Victoria , Cosio Borja G. , Fletton Kirsty , Hansen Susanne , Heaney Liam G. , Hubbard Richard B. , Kuna Piotr , Murray Ruth B. , Nagano Tatsuya , Pini Laura , Cano Rosales Diana Jimena , Schleich Florence , Wechsler Michael E. , Amaral Rita , Bourdin Arnaud , Brusselle Guy G. , Chen Wenjia , Chung Li Ping , Denton Eve , Fonseca Joao A. , Hoyte Flavia , Jackson David J. , Katial Rohit , Kirenga Bruce J. , Koh Mariko Siyue , Ławkiedraj Agnieszka , Lehtimäki Lauri , Liew Mei Fong , Mahboub Bassam , Martin Neil , Menzies-Gow Andrew N. , Pang Pee Hwee , Papaioannou Andriana I. , Patel Pujan H. , Perez-De-Llano Luis , Peters Matthew J. , Ricciardi Luisa , Rodríguez-Cáceres Bellanid , Solarte Ivan , Tay Tunn Ren , Torres-Duque Carlos A. , Wang Eileen , Zappa Martina , Abisheganaden John , Assing Karin Dahl , Costello Richard W. , Gibson Peter G. , Heffler Enrico , Máspero Jorge , Nicola Stefania , Perng (Steve) Diahn-Warng , Puggioni Francesca , Salvi Sundeep , Sheu Chau-Chyun , Sirena Concetta , Taillé Camille , Tan Tze Lee , Bjermer Leif , Canonica Giorgio Walter , Iwanaga Takashi , Jiménez-Maldonado Libardo , Taube Christian , Brussino Luisa , Price David B. 
Published: April 2024

Background

To date, studies investigating the association between pre-biologic biomarker levels and post-biologic outcomes have been limited to single biomarkers and assessment of biologic efficacy from structured clinical trials.

Aim

To elucidate the associations of pre-biologic individual biomarker levels or their combinations with pre-to-post biologic changes in asthma outcomes in real-life.

Methods

This was a registry-based, cohort study using data from 23 countries, which shared data with the International Severe Asthma Registry (May 2017-February 2023). The investigated biomarkers (highest pre-biologic levels) were immunoglobulin E (IgE), blood eosinophil count (BEC) and fractional exhaled nitric oxide (FeNO). Pre- to approximately 12-month post-biologic change for each of three asthma outcome domains (i.e. exacerbation rate, symptom control and lung function), and the association of this change with pre-biologic biomarkers was investigated for individual and combined biomarkers.

Results

Overall, 3751 patients initiated biologics and were included in the analysis. No association was found between pre-biologic BEC and pre-to-post biologic change in exacerbation rate for any biologic class. However, higher pre-biologic BEC and FeNO were both associated with greater post-biologic improvement in FEV1 for both anti-IgE and anti-IL5/5R, with a trend for anti-IL4Rα. Mean FEV1 improved by 27-178 mL post-anti-IgE as pre-biologic BEC increased (250 to 1000 cells/µL), and by 43-216 mL and 129-250 mL post-anti-IL5/5R and -anti-IL4Rα, respectively along the same BEC gradient. Corresponding improvements along a FeNO gradient (25-100 ppb) were 41-274 mL, 69-207 mL and 148-224 mL for anti-IgE, anti-IL5/5R, and anti-IL4Rα, respectively. Higher baseline BEC was also associated with lower probability of uncontrolled asthma (OR 0.392; p=0.001) post-biologic for anti-IL5/5R. Pre-biologic IgE was a poor predictor of subsequent pre-to-post-biologic change for all outcomes assessed for all biologics. The combination of BEC + FeNO marginally improved the prediction of post-biologic FEV1 increase (adjusted R2: 0.751), compared to BEC (adjusted R2: 0.747) or FeNO alone (adjusted R2: 0.743) (p=0.005 and &lt;0.001, respectively); however, this prediction was not improved by the addition of IgE.

Conclusions

The ability of higher baseline BEC, FeNO and their combination to predict biologic-associated lung function improvement may encourage earlier intervention in patients with impaired lung function or at risk of accelerated lung function decline.