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. 2024 Oct;79(10):2700-2716.
doi: 10.1111/all.16178. Epub 2024 Jun 22.

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

Eve Denton  1   2 , Mark Hew  1   3 , Matthew J Peters  4   5 , John W Upham  6 , Lakmini Bulathsinhala  7   8 , Trung N Tran  9 , Neil Martin  9   10 , Celine Bergeron  11   12 , Mona Al-Ahmad  13   14 , Alan Altraja  15 , Désirée Larenas-Linnemann  16 , Ruth Murray  7 , Carlos Andrés Celis-Preciado  17   18 , Riyad Al-Lehebi  19   20 , Manon Belhassen  21 , Mohit Bhutani  22 , Sinthia Z Bosnic-Anticevich  23   24 , Arnaud Bourdin  25 , Guy G Brusselle  26   27 , John Busby  28 , Giorgio Walter Canonica  29   30 , Enrico Heffler  29   30 , Kenneth R Chapman  31 , Jérémy Charriot  25 , George C Christoff  32 , Li Ping Chung  33 , Borja G Cosio  34 , Andréanne Côté  35 , Richard W Costello  36 , Breda Cushen  37 , James Fingleton  38 , João A Fonseca  39 , Peter G Gibson  40   41 , Liam G Heaney  42 , Erick Wan-Chun Huang  43 , Takashi Iwanaga  44 , David J Jackson  45 , Mariko Siyue Koh  46 , Lauri Lehtimäki  47   48 , Jorge Máspero  49   50 , Bassam Mahboub  51 , Andrew N Menzies-Gow  52   53 , Patrick D Mitchell  54 , Nikolaos G Papadopoulos  55   56 , Andriana I Papaioannou  57 , Luis Perez-de-Llano  58 , Diahn-Warng Perng  59   60 , Paul E Pfeffer  61   62 , Todor A Popov  63 , Celeste M Porsbjerg  64 , Chin Kook Rhee  65 , Nicolas Roche  66 , Mohsen Sadatsafavi  67 , Sundeep Salvi  68 , Johannes Martin Schmid  69 , Chau-Chyun Sheu  70   71 , Concetta Sirena  72 , Carlos A Torres-Duque  73   74 , Laila Salameh  51   75 , Pujan H Patel  76 , Charlotte Suppli Ulrik  77 , Eileen Wang  78 , Michael E Wechsler  79 , David B Price  7   8   80 ; ISAR LUMINANT Working Group
Affiliations
Free article

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

Eve Denton et al. Allergy. 2024 Oct.
Free article

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 (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.

Keywords: International Severe Asthma Registry (ISAR); asthma; biologics; clinical response; monoclonal antibodies; super‐responders.

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