The main clinical evidence came from a double-blind placebo-controlled randomised trial, QUEST. This trial compared dupilumab with placebo in 948 people 12 years and over with persistent asthma who had 1 or more exacerbations in the previous 12 months. It included people with moderate to severe asthma, who were not on maintenance oral corticosteroids. In QUEST, the coprimary outcome was annualised rate of severe exacerbations and change from baseline in the forced expiratory volume in 1 second (FEV1) at 12 weeks. There was a 47.7% lower rate of severe exacerbations in the dupilumab group compared with placebo. There was an increase in FEV1 at 12 weeks when dupilumab was compared with placebo in QUEST. The committee concluded that dupilumab was more clinically effective than standard care in the clinical trial population. The company proposes dupilumab 200 mg for very severe asthma with type 2 inflammation in people not eligible for mepolizumab, reslizumab or benralizumab, or whose asthma has not adequately responded to these biological treatments. This is a narrower population than that in the marketing authorisation. It represents people with the highest unmet need and people only eligible for standard care. Dupilumab could be a valuable treatment option in these people because, without it, they will need regular oral corticosteroids. The company's updated base-case deterministic incremental cost-effectiveness ratio (ICER) for dupilumab compared with standard care was £28,156 per QALY gained in people with a blood eosinophil count of 150 cells per microlitre or more and FeNo of 25 parts per billion or more, who have had at least 4 or more exacerbations in the previous 12 months, and who are not eligible for mepolizumab, reslizumab or benralizumab or whose asthma has not responded adequately to these biological therapies. The committee was aware that all the explored scenarios had minimal effect on the cost-effectiveness results. It noted, however, that the base-case model should have included the mortality correction, which increased the ICER to £28,929 per QALY gained. The committee noted that this was at the higher end of what NICE usually considers a cost-effective use of NHS resources. However, it considered dupilumab to be innovative as an additional treatment for people with severe asthma with type 2 inflammation and a high unmet need. It also noted that the model did not take into account the costs and disutilities associated with long-term oral corticosteroid use (that is, obesity, diabetes, osteoporosis, cataracts, hypertension, adrenal suppression, anxiety and depression). Also, some people with comorbidities such as nasal polyps and atopic dermatitis would get additional benefits from dupilumab. The committee considered dupilumab to be a step change for people with severe asthma with type 2 inflammation. Therefore, it concluded that the ICER of £28,929 per QALY was likely to represent the upper estimate of the cost effectiveness of dupilumab.