Real‐world biologics response and super‐response in the International Severe Asthma Registry cohort
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. ,   the ISAR LUMINANT Working Group
Published: June 2024

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.