Dupilumab reduces itch, improves skin lesions in prurigo nodularis

Dupilumab improves itch response and skin lesions in patients with prurigo nodularis (PN) inadequately controlled with prior therapies in the LIBERTY-PN PRIME trial.

At 24 weeks, nearly 60 percent of patients treated with dupilumab had itch reduction vs 18.4 percent with placebo.

“The most important finding is the robust itch reduction, as well as the significant improvement in the fibrotic lesions, as previous nonspecific treatments were not as effective,” said study investigator Dr Gil Yosipovitch from the Miller School of Medicine at the University of Miami, and Director of the Miami Itch Center in Miami, Florida, US, at EADV 2022. “Dupilumab opens a new era for targeted safe treatments for PN patients with unrelenting disease.”

No approved therapy for PN

“PN is one of the most challenging conditions dermatologists deal with due to the relentless, chronic itch patients have been suffering for years, along with the fibrotic nodular disfiguring lesions,” said Yosipovitch. “There are currently no US FDA- or EMA-approved drugs for PN.”

LIBERTY-PN PRIME compared dupilumab with a placebo in 151 adults with PN who had 20–100 nodules (Investigator’s Global Assessment PN-Stage [IGA PN-S] score 3 or 4), and a severe itch that was uncontrolled with topical and systemic therapies. The mean Worst Itch-Numeric Rating Scale (WI-NRS) score at baseline was 8.5. The mean skin pain score was 7.2. [EADV 2022, abstract 3583]

“The quality of life for these patients was low and their scores on the Hospital Anxiety and Depression scale indicated they were depressed,” said Yosipovitch. They were randomly assigned to dupilumab 300 mg given intravenously, after a 600-mg loading dose, or a placebo every 2 weeks for 24 weeks. Patients were allowed to continue treatment with topical steroids or calcineurin inhibitors if they had been taking them at baseline.

At 24 weeks, there were more patients on dupilumab vs placebo who had a significant improvement in the primary endpoint of WI-NRS score of ≥4-point from baseline (60 percent vs 18.4 percent; p<0.0001). Similarly, more patients on dupilumab vs placebo (48 percent vs 18.4 percent; p=0.0004) achieved an IGA PN-S score of 0 or 1 (0=clear, 1=almost clear).

Treatment-emergent adverse events (TEAEs) were similar between groups (70.7 percent vs 62.7 percent for dupilumab vs placebo) so were the rates of severe TEAEs (6.7 percent and 10.7 percent, respectively).

Dupilumab is an interleukin-4 receptor alpha antagonist currently under regulatory review in the US and Europe for the treatment of PN. The drug is US-FDA approved for atopic dermatitis.

There can be a honeymoon period during which dupilumab may be stopped after 24 weeks of use, said Yosipovitch during a discussion following his presentation. “However, patients would need treatment for the rest of their lives.”