Background: This initiative aimed to elucidate the clinical relevance of type 2 (T2) inflammation as a driver of asthma, atopic dermatitis, chronic rhinitis, chronic rhinosinusitis with nasal polyps (CRSwNP) and eosinophilic esophagitis. Methods: A steering committee (SC) conducted a non-systematic literature search to inform the design of a Delphi questionnaire including 23 consensus statements, which was circulated to 30 experts including the SC. Experts rated their agreement with each statement on a 9-point Likert scale and provided optional feedback that was used to develop a second Delphi questionnaire. On 22 October 2020, a meeting was held to discuss the conclusions from the questionnaires and explore how this initiative may impact the management of patients with T2 inflammation-driven disease. Post meeting, a consensus statement on the role of T2 inflammation in eosinophilic esophagitis was circulated to the experts. Results: It was agreed that T2 inflammation may be an underlying driver of asthma, atopic dermatitis, chronic rhinitis, CRSwNP and eosinophilic esophagitis, and that the published evidence suggests that these diseases overlap. Some of this overlap may include related multimorbid conditions driven by T2 inflammation. Thus, in patients with multiple T2 inflammation-driven diseases, a cross-speciality approach is warranted to provide effective care. A question guide with input from relevant experts was proposed, to identify comorbidities and facilitate appropriate holistic patient management. Conclusions: These consensus recommendations should be used as a framework to further understand the extent of T2 inflammation-driven multi-organ disease and to improve the holistic management and care of these patients.

Background Patients with severe asthma may present with characteristics representing overlapping phenotypes, making them eligible for more than one class of biologic. Our aim was to describe the profile of severe adult asthma patients eligible for both anti-IgE and anti-IL5/5R and to compare the effectiveness of both classes of treatment in real life. Methods This was a prospective cohort study that included adult severe asthma patients from 22 countries enrolled into the International Severe Asthma registry (ISAR) who were eligible for both anti-IgE and anti-IL5/5R. The effectiveness of anti-IgE and anti-IL5/5R was compared in a 1:1 matched cohort. Exacerbation rate was the primary effectiveness endpoint. Secondary endpoints included long-term-oral corticosteroid (LTOCS) use, asthma-related emergency room (ER) attendance and hospital admissions. Results In the matched analysis (n=350/group), the mean annualized exacerbation rate decreased by 47.1% in the anti-IL5/5R group and 38.7% in the anti-IgE group. Patients treated with anti-IL5/5R were less likely to experience a future exacerbation (adjusted IRR 0.76; 95% CI 0.64, 0.89; p<0.001) and experienced a greater reduction in mean LTOCS dose than those treated with anti-IgE (37.44% vs 20.55% reduction; p=0.023).) There was some evidence to suggest that patients treated with anti-IL5/5R experienced fewer asthma-related hospitalizations (IRR 0.64; 95% CI 0.38, 1.08), but not ER visits (IRR 0.94, 95% CI 0.61, 1.43). Conclusions In real life, both anti-IgE and anti-IL5/5R improve asthma outcomes in patients eligible for both biologic classes, however anti-IL5/5R was superior in terms of reducing asthma exacerbations and LTOCS use.