Real‐world biologics response and super‐response in the International Severe Asthma Registry cohort

• Published in: Allergy (Copenhagen) 2024-10, Vol.79 (10), p.2700-2716
• Main Authors: Denton, Eve, Hew, Mark, Peters, Matthew J., Upham, John W., Bulathsinhala, Lakmini, Tran, Trung N., Martin, Neil, Bergeron, Celine, Al‐Ahmad, Mona, Altraja, Alan, Larenas‐Linnemann, Désirée, Murray, Ruth, Celis‐Preciado, Carlos Andrés, Al‐Lehebi, Riyad, Belhassen, Manon, Bhutani, Mohit, Bosnic‐Anticevich, Sinthia Z., Bourdin, Arnaud, Brusselle, Guy G., Busby, John, Canonica, Giorgio Walter, Heffler, Enrico, Chapman, Kenneth R., Charriot, Jérémy, Christoff, George C., Chung, Li Ping, Cosio, Borja G., Côté, Andréanne, Costello, Richard W., Cushen, Breda, Fingleton, James, Fonseca, João A., Gibson, Peter G., Heaney, Liam G., Huang, Erick Wan‐Chun, Iwanaga, Takashi, Jackson, David J., Koh, Mariko Siyue, Lehtimäki, Lauri, Máspero, Jorge, Mahboub, Bassam, Menzies‐Gow, Andrew N., Mitchell, Patrick D., Papadopoulos, Nikolaos G., Papaioannou, Andriana I., Perez‐de‐Llano, Luis, Perng, Diahn‐Warng, Pfeffer, Paul E., Popov, Todor A., Porsbjerg, Celeste M., Rhee, Chin Kook, Roche, Nicolas, Sadatsafavi, Mohsen, Salvi, Sundeep, Schmid, Johannes Martin, Sheu, Chau‐Chyun, Sirena, Concetta, Torres‐Duque, Carlos A., Salameh, Laila, Patel, Pujan H., Ulrik, Charlotte Suppli, Wang, Eileen, Wechsler, Michael E., Price, David B.
• Format: Article
• Language: English
• Subjects: Allergology; Asthma; Biological products; biologics; Biomarkers; Biopharmaceuticals; clinical response; Clinical trials; Corticosteroids; Immunology; Interleukin 5 receptors; International Severe Asthma Registry (ISAR); Life Sciences; monoclonal antibodies; Patients; Santé publique et épidémiologie; super‐responders
• ISSN: 0105-4538; 1398-9995; 1398-9995
• DOI: 10.1111/all.16178

Background Biologic asthma therapies reduce exacerbations and long‐term oral corticosteroids (LTOCS) use in randomized controlled trials (RCTs); however, there are limited data on outcomes among patients ineligible for RCTs. Hence, we investigated responsiveness to biologics in a real‐world population of adults with severe asthma. Methods Adults in the International Severe Asthma Registry (ISAR) with ≥24 weeks of follow‐up were grouped into those who did, or did not, initiate biologics (anti‐IgE, anti‐IL5/IL5R, anti‐IL4/13). Treatment responses were examined across four domains: forced expiratory volume in 1 second (FEV1) increase by ≥100 mL, improved asthma control, annualized exacerbation rate (AER) reduction ≥50%, and any LTOCS dose reduction. Super‐response criteria were: FEV1 increase by ≥500 mL, new well‐controlled asthma, no exacerbations, and LTOCS cessation or tapering to ≤5 mg/day. Results 5.3% of ISAR patients met basic RCT inclusion criteria; 2116/8451 started biologics. Biologic initiators had worse baseline impairment than non‐initiators, despite having similar biomarker levels. Half or more of initiators had treatment responses: 59% AER reduction, 54% FEV1 increase, 49% improved control, 49% reduced LTOCS, of which 32%, 19%, 30%, and 39%, respectively, were super‐responses. Responses/super‐responses were more frequent in biologic initiators than in non‐initiators; nevertheless, ~40–50% of initiators did not meet response criteria. Conclusions Most patients with severe asthma are ineligible for RCTs of biologic therapies. Biologics are initiated in patients who have worse baseline impairments than non‐initiators despite similar biomarker levels. Although biologic initiators exhibited clinical responses and super‐responses in all outcome domains, 40–50% did not meet the response criteria. Data on real‐world responsiveness to biologic asthma therapies are lacking. Only ~5% of International Severe Asthma Registry (ISAR) patients met biologic randomized controlled trial eligibility criteria. Compared with ISAR non‐biologic users, biologic initiators had more frequent responses/super‐responses (lower exacerbation rate, improved lung function and asthma control, and diminished oral corticosteroids use); nevertheless, 40%–50% did not meet clinical response criteria.Abbreviations: AER, annualized exacerbation rate; FEV1, forced expiratory volume in 1 second; ISAR, International Severe Asthma Registry; OCS, oral corticosteroids.