What clinical features push you to add dupilumab instead of escalating ICS dose in a patient with biomarker-high asthma and recurrent exacerbations?

The Phase 3 QUEST study addressed this question and found that adding dupilumab to medium-dose ICS/LABA provided significantly better control than placebo plus high-dose ICS. However, this study did not look at actual dose escalation of the ICS prior to instituting the biologic. They also found no significant impact of either Montelukast or anticholinergic therapy. So, on the surface, it would seem that prompt progression to a biologic (in this case dupilumab) in a moderately severe asthma patient would be a viable option. However, in my experience, it is common for insurance to deny biologic coverage (of any kind) unless/until the patient has failed ICS dose escalation since the indications for biologics are for severe asthma inadequately ...

I would consider adding dupilumab if the patient is already on twice-daily high-dose ICS/LABA; as many studies suggest meaningful improvement only occurs in this setting if you increase the ICS 2-4x. At that higher ICS level, typically > 1000 µg daily, the patient is likely to encounter dysphonia, thrush, or even signs of systemic steroid side effects over time. The decision is even easier if the patient also has other conditions that would likely benefit from dupilumab (as these patients often do) e.g., chronic rhinosinusitis with nasal polyps, moderate to severe atopic dermatitis, eosinophilic esophagitis, COPD, and/or chronic spontaneous urticaria.

This study represents a post hoc analysis of the Phase 3 QUEST study in patients 12 and older with uncontrolled, moderate-to-severe asthma. It included 1582 patients with Type 2 inflammatory asthma and demonstrated that dupilumab + medium-dose inhaled steroids decreased asthma exacerbations by 70% compared to high-dose ICS + placebo.

In a systematic review and meta-analysis in Chest (Noble et al., PMID 40912294), maintenance high-dose ICS/LABA decreased the odds of a severe exacerbation by about 20% compared with medium-dose ICS/LABA. The absolute risk reduction depended on the baseline exacerbation risk. There were no other benefits, including no other clinically relevant improvements, such as in FEV1 or asthma symptoms. In this post hoc an...