Wechsler ME, Scelo G, Larenas-Linnemann DES et al. Am J Respir Crit Care Med. 2024 Feb 1;209(3):262-272. doi: 10.1164/rccm.202305-0808OC.
Abstract
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.
Scientific Knowledge on the Subject
Although the effectiveness of biologic agents in treating patients with asthma who have a type 2–related comorbidity is documented, the influence of comorbidities on the effectiveness of biologic therapy is less studied.
What This Study Adds to the Field
We investigated the association of four potentially type 2–related comorbidities on the effectiveness of biologic therapy 1) overall and by class and 2) measured across four asthma outcomes and 3) directly compared biologic agent effectiveness in patients with and without a given comorbidity. We found that most patients treated with biologic therapy exhibited an improvement in each asthma-related outcome assessed, irrespective of the presence of a comorbidity. However, additional improvements in exacerbation rate, asthma control, and lung function were noted in patients with chronic rhinosinusitis with or without nasal polyps (NPs) and in those with NPs compared with those without NPs, even after adjusting for blood eosinophil count. Our findings suggest that patients with severe asthma and chronic rhinosinusitis with or without NPs or NPs alone may benefit more from biologic therapy than those without these comorbidities, emphasizing the need for systematic comorbidity evaluation and a multidisciplinary approach to the management of severe asthma.