Association Between T2-related Comorbidities and Effectiveness of Biologics in Severe Asthma

Michael E Wechsler, Ghislaine Scelo, Désirée E S Larenas-Linnemann, Carlos A Torres-Duque, Jorge Maspero, Trung N Tran, Ruth B Murray, Neil Martin, Andrew N Menzies-Gow, Mark Hew, Matthew J Peters, Peter G Gibson, George C Christoff, Todor A Popov, Andréanne Côté, Celine Bergeron, Delbert Dorscheid, J Mark FitzGerald, Kenneth R Chapman, Louis Philippe BouletMohit Bhutani, Mohsen Sadatsafavi, Libardo Jiménez-Maldonado, Mauricio Duran-Silva, Bellanid Rodriguez, Carlos Andres Celis-Preciado, Diana Jimena Cano-Rosales, Ivan Solarte, Maria Jose Fernandez-Sanchez, Patricia Parada-Tovar, Anna von Bülow, Anne Sofie Bjerrum, Charlotte S Ulrik, Karin Dahl Assing, Linda Makowska Rasmussen, Susanne Hansen, Alan Altraja, Arnaud Bourdin, Camille Taille, Jeremy Charriot, Nicolas Roche, Andriana I Papaioannou, Konstantinos Kostikas, Nikolaos G Papadopoulos, Sundeep Salvi, Deirdre Long, Patrick D Mitchell, Richard Costello, Concetta Sirena, Cristina Cardini, Enrico Heffler, Francesca Puggioni, Giorgio Walter Canonica, Giuseppe Guida, Takashi Iwanaga, Mona Al-Ahmad, Ulises García, Piotr Kuna, João A Fonseca, Riyad Al-Lehebi, Mariko S Koh, Chin Kook Rhee, Borja G Cosio, Luis Perez de Llano, Diahn-Warng Perng, Erick Wan-Chun Huang, Hao-Chien Wang, Ming-Ju Tsai, Bassam Mahboub, Laila Ibraheem Jaber Salameh, David J Jackson, John Busby, Liam G Heaney, Paul E Pfeffer, Amanda Grippen Goddard, Eileen Wang, Flavia C L Hoyte, Nicholas M Chapman, Rohit Katial, Victoria Carter, Lakmini Bulathsinhala, Neva Eleangovan, Con Ariti, Juntao Lyu, Celeste Porsbjerg, David B Price


Rationale: Previous studies investigating the impact of comorbidities on the effectiveness of biologic agents have been relatively small and of short duration and have not compared classes of biologic agents. Objectives: To determine the association between type 2-related comorbidities and biologic agent effectiveness in adults with severe asthma (SA). Methods: This cohort study used International Severe Asthma Registry data from 21 countries (2017-2022) to quantify changes in four outcomes before and after biologic therapy-annual asthma exacerbation rate, FEV1% predicted, asthma control, and long-term oral corticosteroid daily dose-in patients with or without allergic rhinitis, chronic rhinosinusitis (CRS) with or without nasal polyps (NPs), NPs, or eczema/atopic dermatitis. Measurements and Main Results: Of 1,765 patients, 1,257, 421, and 87 initiated anti-IL-5/5 receptor, anti-IgE, and anti-IL-4/13 therapies, respectively. In general, pre- versus post-biologic therapy improvements were noted in all four asthma outcomes assessed, irrespective of comorbidity status. However, patients with comorbid CRS with or without NPs experienced 23% fewer exacerbations per year (95% CI, 10-35%; P < 0.001) and had 59% higher odds of better post-biologic therapy asthma control (95% CI, 26-102%; P < 0.001) than those without CRS with or without NPs. Similar estimates were noted for those with comorbid NPs: 22% fewer exacerbations and 56% higher odds of better post-biologic therapy control. Patients with SA and CRS with or without NPs had an additional FEV1% predicted improvement of 3.2% (95% CI, 1.0-5.3; P = 0.004), a trend that was also noted in those with comorbid NPs. The presence of allergic rhinitis or atopic dermatitis was not associated with post-biologic therapy effect for any outcome assessed. Conclusions: These findings highlight the importance of systematic comorbidity evaluation. The presence of CRS with or without NPs or NPs alone may be considered a predictor of the effectiveness of biologic agents in patients with SA.

Original languageEnglish
JournalAmerican Journal of Respiratory and Critical Care Medicine
Issue number3
Pages (from-to)262-272
Number of pages11
Publication statusPublished - 1 Feb 2024


  • Adult
  • Asthma/complications
  • Biological Products/therapeutic use
  • Chronic Disease
  • Cohort Studies
  • Comorbidity
  • Humans
  • Nasal Polyps/complications
  • Rhinitis, Allergic/complications
  • Rhinitis/complications
  • Sinusitis/drug therapy


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