Prurigo nodularis causes intense, persistent itch, with thick skin nodules that can cover most of the body.
Treatment with dupilumab (Dupixent) was found to significantly improve itch and skin lesions in patients with prurigo nodularis (PN), according to data from the LIBERTY-PN PRIME2 trial presented at the American Academy of Dermatology 2022 Annual Meeting.
PN, a chronic inflammatory skin disease, causes intense, persistent itch, with thick nodules that can cover most of the body. It is frequently described as causing a burning, stinging, and tingling of the skin.
“Prurigo nodularis is a relentless and often misunderstood itchy skin disease that leaves many patients with uncontrolled symptoms such as unbearable itch and painful skin lesions, along with a significantly impaired quality of life that should not be underestimated,” said principal investigator of the PRIME2 trial, Gil Yosipovitch, MD, professor of Dermatology, Miller School of Medicine, University of Miami, in a press release. “These positive results are the first time a phase 3 trial has demonstrated that targeting key drivers of type 2 inflammation, IL-4 and IL-13, with dupilumab significantly improved itch and skin lesions in this highly burdensome disease.”
Uncontrolled PN can have a highly detrimental impact on quality of life, negatively affecting mental health, daily activities, and social interactions. Currently, there are no FDA-approved treatments for PN, with high-potency topical steroids the most commonly prescribed therapy; however, long-term use of these drugs are associated with safety risks.
Off-label treatments, such as topical treatments and ultraviolet light, have frequently resulted in inadequate control in patients with ≥20 lesions, and many off-label systemic therapies have limited evidence and various adverse effects and toxicities.
In the phase 3 LIBERTY-PN PRIME2 trial, adult patients with 20 or more nodules and severe itch were considered for dupilumab treatment. At baseline among the study participants with PN, the mean Worst-Itch Numeric Rating Scale (WI-NRS) was 8.5 (1.0), 62% had ≥20 to 100 nodules, 38% had >100 nodules. Nearly two-thirds of these patients had previously used systemic therapies. In total, 78 adults with PN were administered a 600 mg loading dose of dupilumab followed by 300 mg doses every 2 weeks for a total of 24 weeks.
The primary endpoint was a proportion of patients experiencing a ≥4-point reduction on the WI-NRS (range: 0-10) from baseline to week 12. Key secondary endpoints included proportions of patients with ≥4-point reduction in WI-NRS from baseline to week 24, and Investigator’s Global Assessment PN-Stage (IGA PN-S, range: 0-4] of 0 or 1 at week 24.
In patients treated with dupilumab, 37.2% achieved ≥4-point reduction in WI-NRS at W12 (P=0.0216) compared with 22.0% of placebo-treated patients, and 57.7% of patients treated with dupilumab achieved a ≥4-point reduction at week 24 (P<0.0001) compared with 19.5% of placebo-treated patients.
Further, 44.9% of patients with PN administered dupilumab achieved IGA PN-S of 0 or 1 at week 24 versus 15.9% of the placebo cohort (P<0.0001). The rate of treatment-emergent adverse events was 57.1% and 51.2% for dupilumab and placebo, respectively.
The safety profile was consistent with the known safety profile of dupilumab.
Beyond dupilumab’s current indications, it is also being evaluated in clinical trials across several diseases driven by type 2 inflammation or other allergic processes, such as pediatric atopic dermatitis; hand and foot atopic dermatitis; eosinophilic esophagitis; chronic spontaneous urticaria; bullous pemphigoid; chronic inducible urticaria-cold; chronic obstructive pulmonary disease with evidence of type 2 inflammation; chronic rhinosinusitis without nasal polyposis; allergic fungal rhinosinusitis; allergic bronchopulmonary aspergillosis; and peanut allergy.