Dupilumab is first systemic therapy to show positive Phase 3 results in patients with moderate-to-severe atopic dermatitis, a serious, chronic inflammatory skin disease marked by widespread rash, itching and associated psychosocial comorbidities. In the studies, known as LIBERTY AD SOLO 1 and SOLO 2, treatment with dupilumab as monotherapy significantly improved measures of overall disease severity, skin clearing, itching, quality of life, and mental health.
A total of 1,379 adult patients with moderate-to-severe AD were enrolled in the identically-designed SOLO 1 and SOLO 2 trials. Patients were enrolled if they were not adequately controlled with topical medications, or if topical treatment was not medically advisable. All patients were assessed via the 5-point Investigator’s Global Assessment (IGA) scale, ranging from 0 (clear) to 4 (severe); entry criteria required a baseline score of 3 or 4. Patients were also assessed using the Eczema Area and Severity Index (EASI) and other measures. Patients were randomized into one of three treatment groups: dupilumab 300 mg subcutaneously once per week, dupilumab 300 mg subcutaneously every two weeks, or placebo for 16 weeks following an initial dupilumab loading dose of 600 mg subcutaneously, or placebo. For SOLO 1 and SOLO 2, respectively, 37 and 36% of patients who received dupilumab 300 mg weekly, and 38 and 36% of patients who received dupilumab 300 mg every two weeks, achieved clearing or near-clearing of skin lesions (IGA 0 or 1), compared to 10 and 8.5% with placebo (p less than 0.0001). This was the primary endpoint of the study in the U.S.
Moreover, for SOLO 1 and SOLO 2, respectively, the% improvement in EASI from baseline was 72 and 69% in patients who received the 300 mg weekly dose, and 72 and 67% for patients who received dupilumab 300 mg every two weeks, compared to 38 and 31% for placebo (p less than 0.0001). Last, for SOLO 1 and SOLO 2, respectively, 52.5 and 48% of patients who received dupilumab 300 mg weekly, and 51 and 44% of patients who received dupilumab 300 mg every two weeks, achieved EASI-75 compared to 15 and 12% with placebo (p less than 0.0001). This was the key secondary endpoint in the US for these studies and one of the primary endpoints in the EU.
For the 16-week treatment period, the overall rate of adverse events (65-73% dupilumab and 65-72% placebo) was comparable between the dupilumab groups and the placebo groups. The proportion of patients who completed the treatment period was 88-94% for dupilumab and 80.5-82% for placebo. The rate of serious adverse events was 1-3% for dupilumab and 5-6% for placebo. Serious and severe infections were also numerically higher in the placebo groups in both studies (0.5-1% dupilumab and 2-3% placebo). Adverse events that were noted to have a higher rate with dupilumab treatment across both studies included injection site reactions (10-20% dupilumab; 7-8% placebo), conjunctivitis (7-12% dupilumab; 2% placebo); approximately 26% of patients in both studies reported a history of allergic conjunctivitis at study entry. No patient discontinued therapy due to injection site reactions and only one patient discontinued therapy due to conjunctivitis.