Dupilumab cuts exacerbations in difficult-to-treat type 2 asthma

Dupilumab effectively prevents severe asthma exacerbations and improves lung function in patients with difficult-to-treat type 2 asthma, according to a post hoc analysis of the LIBERTY ASTHMA QUEST study presented at AAAAI 2021.

Previously, add-on dupilumab has been shown to significantly reduce severe exacerbations and improve prebronchodilator (pre-BD) FEV₁ in patients with uncontrolled, moderate-to-severe asthma in the primary analysis. The data also revealed that the treatment benefits were more pronounced in patients who showed increased type 2 biomarkers at baseline: blood eosinophils ≥150 cells/µL or fractional exhaled nitric oxide (FeNO) ≥25 parts per billion (ppb).

According to recent GINA* guidelines, add-on biologic therapy is recommended for patients with severe type 2 asthma, which was defined as having any of the criteria as followed: FeNO ≥20 ppb, blood eosinophils ≥150 cells/µL, sputum eosinophils ≥2 percent, need for maintenance oral corticosteroids, and/or evidence of clinically allergen-driven disease.

Therefore, a post hoc analysis of LIBERTY ASTHMA QUEST was conducted to on patients with three elements of type 2 criteria as defined by GINA, rather than individual biomarkers (reported in the primary findings).

This difficult-to-treat population (n=534) in the post hoc analysis was identified by elevated levels of type 2 biomarkers at baseline (ie, FeNO ≥20 ppb and blood eosinophils ≥150 cells/µL) and evidence of allergic asthma. Patients were randomized to receive dupilumab 200 mg or 300 mg Q2W or matching placebo for 52 weeks. [AAAAI 2021, abstract 183]

“The majority of QUEST patients [who satisfied the three criteria] presented an ongoing comorbid condition, with allergic rhinitis being the most common [over 75 percent],” the researchers pointed out.

In this difficult-to-treat population with GINA-defined type 2 asthma, treatment with dupilumab led to significantly reduced rate of severe exacerbations by 57.4 percent (both doses combined) compared with placebo (p<0.0001). The individual adjusted hazard ratio (HR) was 0.39 for the 200 mg dupilumab dose and 0.45 for the 300 mg dose (p<0.001 for both).

Similarly, lung function as assessed by pre-BD FEV₁ was also significantly improved with dupilumab vs placebo throughout 52 weeks of treatment (least squares mean difference at week 12, 0.24 L; p<0.0001).

Long-term efficacy in allergic phenotype

To study the long-term efficacy of dupilumab, patients from the LIBERTY ASTHMA QUEST were rolled into the open-label extension study, LIBERTY ASTHMA TRAVERSE.

The new post hoc analysis involved a slightly different population (n=1,530), also with allergic phenotype (total serum IgE ≥30 IU/mL and ≥1 perennial aeroallergen-specific IgE ≥0.35 kU/L at parent study baseline) but with no minimum requirement for type 2 biomarkers, unlike the above analysis. [AAAAI 2021, abstract 184]

“Dupilumab efficacy was sustained in patients with uncontrolled, moderate-to-severe asthma with or without an allergic phenotype for up to 3 years,” reported the researchers.

During the double-blind phase in QUEST, add-on dupilumab led to fewer severe exacerbations than placebo, regardless of whether patients were allergic (unadjusted rate, 0.520 vs 0.964) or not (unadjusted rate, 0.521 vs 1.134). Consistent benefit was also seen in a subgroup of patients with allergy and eosinophil <150 cells/µL (unadjusted rate, 0.549 vs 0.665).  

The rates of severe exacerbations were further reduced throughout the open-label extension phase in TRAVERSE whereby all patients received dupilumab regardless of their previous treatment assignment in QUEST. Again, the benefit with dupilumab treatment persisted irrespective of patients’ allergic status (unadjusted rate, 0.332 vs 0.375 for allergic and 0.330 vs 0.321 for nonallergic).

In addition, the improvement in lung function with dupilumab during QUEST (change in FEV₁, 0.36 L vs 0.19 L for allergic patients and 0.35 L vs 0.19 L for nonallergic patients) continued through week 96 in TRAVERSE for both the allergic (0.39 L vs 0.33 L) and nonallergic subgroups (0.35 L vs 0.39 L).

“Patients who switched from the placebo arm in QUEST to dupilumab in the open-label extension experienced similar reductions in severe exacerbation rates and improvements in lung function to those patients who already received dupilumab during the parent study, including allergic patients with low eosinophil counts at parent study baseline, [thus] confirming the early dupilumab results from QUEST,” the researchers pointed out.

*GINA: Global Initiative for Asthma