Dupilumab Creates Rapid, Sustained Responses in Asthma, CRSwNP, and AD

After just the first dose, dupilumab creates clinically meaningful responses in asthma, atopic dermatitis (AD), and chronic rhinosinusitis with nasal polyps (CRSwNP) that are sustained throughout treatment.

The study, published in Journal of Allergy and Clinical Immunology: In Practice, evaluated more than 3000 patients who were enrolled in 5 phase 3 studies of dupilumab: LIBERTY AD SOLO-1, LIBERTY AD SOLO-2, LIBERTY ASTHMA QUEST, LINERTY NP SINUS-24, and LIBERTY NP SINUS-52. All 5 were randomized, double-blind, placebo-controlled trials.

“Type 2 inflammatory comorbidities often overlap, resulting in an increase in overall symptom and disease burden,” the authors explained. “A drug that can rapidly provide clinical benefits simultaneously for these comorbidities by targeting the underlying and shared type 2 inflammatory process may be a more desired option for patients.”

Atopic Dermatitis

LIBERTY AD SOLO-1 and LIBERTY SOLO-2 were identical phase 3 randomized, double-blind, placebo-controlled trials that assessed the efficacy and safety of dupilumab in adults whose moderate to severe AD was inadequately controlled by a topical treatment. There were 671 patients in SOLO-1 and 708 in SOLO-2. For both trials, patients were randomized 1:1:1 to receive dupilumab 300 mg subcutaneously (SC) every week, placebo every week, or dupilumab 300 mg SC every 2 weeks alternating with placebo for a total of 16 weeks.

Just a week after initiating dupilumab, 48.1% of patients achieved a ≥ 50% improvement in Eczema Area and Severity Index, a 3-point or greater improvement in daily peak pruritus assessed by a Numerical Rating Scale, or a 4-point or greater improvement on Dermatology Life Quality Index compared with just 30.2% of patients on placebo. This increased to 67.8% of patients on dupilumab and 36.5% of patients on placebo by 2 weeks and to 76.6% vs 35.0%, respectively, by the end of the 16-week study.

Asthma

In the phase 3 trial LIBERTY ASTHMA QUEST, 1902 patients 12 years and older with uncontrolled moderate to severe asthma were evaluated to assess the efficacy of dupilumab. The patients were randomized 2:2:1:1 to receive add-on dupilumab 200 mg or 300 mg SC every 2 weeks or matched placebos for a total of 52 weeks.

By week 2, 61.6% of patients on dupilumab vs 39.9% on placebo had achieved forced expiratory volume (FEV₁) improvements of ≥ 100 mL and 48.8% on dupilumab had achieved ≥ 200 mL vs 26.3% on placebo. These improvements were sustained through the full 52 weeks. By the end of the study, 65.7% of patients on dupilumab achieved FEV₁ improvements of ≥ 100 mL vs 53.2% on placebo and 55.3% of patients on dupilumab achieved improvements of ≥ 200 mL vs 42.0% on placebo.

Nasal Polyps

LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52 assessed dupilumab added to standard of care in adults with severe CRSwNP that was uncontrolled despite intranasal or systemic corticosteroids over the past 2 years or sinonasal surgery. There were 276 patients enrolled in SINUS-24 who were randomized 1:1 to dupilumab 300 mg SC or placebo every 2 weeks for 24 weeks. In SINUS-52, 448 patients were randomized to dupilumab 300 mg SC every 2 weeks for 52 weeks, dupilumab 300 mg SC every 2 weeks for 24 weeks followed by every 4 weeks, or placebo every 2 weeks for 52 weeks.

By week 2, 55.4% of patients on dupilumab had clinically meaningful improvements in sense of smell—considered a University of Pennsylvania Smell Identification Test score above 18—vs 28.0% of patients on placebo. At 24 weeks, this proportion increased to 72.0% of patients on dupilumab vs 22.9% on placebo.

Patients on dupilumab had improvements in baseline daily nasal congestion/obstruction scores and baseline daily loss of smell by day 1 and day 2, respectively. “The magnitude of improvement continued to increase in dupilumab-treated patients vs placebo for both measures and did not plateau within the first 2 weeks assessed,” the authors wrote.

Responses Progressively Increased

The authors noted that since the proportion of patients receiving dupilumab who achieved clinically meaningful responses continued to increase during treatment, a suboptimal response in the first weeks of treatment may not be enough to discontinue treatment.

“Many patients struggle with medication compliance, and clinicians have difficulties adhering to treatment guidelines,” the authors wrote. “We speculate that achieving a clinically meaningful response within the first weeks of treatment may result in better adherence and strengthen the relationship between clinician and patient.”

Reference

Canonica GW, Bourdin A, Peters AT, et al. Dupilumab demonstrates rapid onset of response across three type 2 inflammatory diseases. J Allergy Clin Immunol Pract. Published online March 5, 2022. doi:10.1016/j.jaip.2022.02.026