Real‐world biologics response and super‐response in the International Severe Asthma Registry cohort
Eve Denton, Mark Hew, Matthew Peters, John W. Upham, Lakmini Bulathsinhala, Trung N. Tran, Neil Martin, Céline Bergeron, Mona Al‐Ahmad, Alan Altraja, Désirée Larenas‐Linnemann, Ruth Murray, C.A. Celis-Preciado, Riyad Al‐Lehebi, Manon Belhassen, Mohit Bhutani, Sinthia Bosnic‐Anticevich, Arnaud Bourdin, Guy Brusselle, John Busby, Giorgio Walter Canonica, Enrico Heffler, Kenneth R. Chapman, Jérémy Charriot, George Christoff, Li Ping Chung, Borja G. Cosío, Andréanne Côté, Richard W. Costello, Breda Cushen, James Fingleton, João Fonseca, Peter G. Gibson, Liam G. Heaney, Wan‐Chun Huang, Takashi Iwanaga, David J. Jackson, Mariko Siyue Koh, Lauri Lehtimäki, Jorge Máspero, Bassam Mahboub, Andrew Menzies‐Gow, Patrick Mitchell, Nikolaos G. Papadopoulos, Andriana Ι. Papaioannou, Luis Pérez de Llano, Diahn‐Warng Perng, Paul Pfeffer, Todor A. Popov, Celeste Porsbjerg, Chin Kook Rhee, Nicolás Roche, Mohsen Sadatsafavi, Sundeep Salvi, Johannes Martin Schmid, Chau‐Chyun Sheu, Concetta Sirena, Carlos A. Torres‐Duque, Laila Salameh, Pujan H. Patel, Charlotte Suppli Ulrik, Eileen Wang, Michael E. Wechsler, David Price, the ISAR LUMINANT Working Group
Abstract
Abstract 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 (FEV 1 ) increase by ≥100 mL, improved asthma control, annualized exacerbation rate (AER) reduction ≥50%, and any LTOCS dose reduction. Super‐response criteria were: FEV 1 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% FEV 1 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.