PRIME, PRIME 2 Data Show 12-, 24-Week Improvements in Patients With Prurigo Nodularis

Clinically meaningful and statistically significant improvements from dupilumab for prurigo nodularis have been seen in the LIBERTY-PN PRIME and PRIME2 trials, which investigated itch response to the interleukin (IL)-4 and IL-13 blocker, at 24 and 12 weeks, respectively, from baseline. Outcomes were compared with those who received placebo.

Findings from the 2 phase 3 randomized, double blind, placebo-controlled, multicenter, parallel group trials were published recently in Nature Medicine. They had the same primary and secondary end points: at least a 4-point improvement in Worst Itch Numeric Rating Scale (WI-NRS; scale, 0 [no itch to 10 [worst imaginable itch]) by week 24 or 12 and nodule reduction to 5 or fewer by week 24 in both, as measured by Investigator Global Assessment for PN-Stage (IGA PN-S) score of 0 or 1 (scale, 0 [clear/no nodules] to 4 [severe/> 100 nodules]), respectively.

There were 151 participants in PRIME (dupilumab, n = 75) from 58 study sites in 8 countries and 160 participants in PRIME2 (dupilumab, n = 78) from 55 study sites in 11 countries.

The treatment regimen for both trials was a day 1 subcutaneous 600-mg loading dose of dupilumab followed by 300-mg dupilumab once every 2 weeks for 24 weeks on top of a stable dose of topical corticosteroids/topical calcineurin inhibitors (TCS/TCI) background therapy. There were also a screening (2-4 weeks) and 12-week posttreatment periods.

In PRIME at week 24, just 18.4% of patients in the placebo group met the primary end point of WI-NRS reduction compared with 60.0% of participants who received dupilumab (95% CI, 27.8%-57.7%; P < .001). This equates to 70% more patients in the dupilumab group seeing pruritis improvement.

For PRIME2 at week 12, similar results were seen. Twenty-two percent of patients in the placebo group saw WI-RNS reduction vs 37.2% of the treatment cohort (95% CI, 2.3%-31.2%; P = .022), for 41% more patients receiving dupilumab experiencing pruritis improvement.

At baseline, the mean (SD) WI-NRS score for all patients in both trials was 8.5 (1.0), indicating severe itch, and all participants reported at least 20 nodules. High numbers of patients in both trials reported at least 100 nodules (28.7%, PRIME; 38.4%, PRIME2).

For the secondary end point of IGA PN-S, in both trials, more patients in the dupilumab group saw an improvement in skin lesions:

• PRIME:
  • 12 weeks: 32.0% vs 11.8% (95% CI, 7.8% 34.0%; P = .003)
  • 24 weeks: 48.0% vs 18.4% (95% CI, 13.4%-43.2%; P < .001)
• PRIME2:
  • 12 weeks: 25.6% vs 12.2% in PRIME2 (95% CI, 2.6%-27.0%; P = .019)
  • 24 weeks: 44.9% vs 15.9% (95% CI,16.4%-45.2; P < .001)

One of the scales used to measure disease severity, the Dermatology Life Quality Index (scale, 0 [no effect on patient’s life] to 30 [extremely large effect]), showed that patients reported prurigo nodularis had a very large impact on their life, with mean scores of 16.7 (7.2) and 18.2 (6.7) in PRIME and PRIME2, respectively. There were also high rates of topical therapies seen, with 98.7% of PRIME participants and 98.1% of PRIME2 participants reporting past TCS use; 69.5% and 63.1%, respectively, reported any systemic therapy use for prurigo nodularis, with antihistamines being the most common, in 58.9% and 48.8%.

In instances where rescue medication was necessary, fewer patients in both trials in the dupilumab groups required this step: in PRIME, 6.7% of patients in the treatment group vs 21.1% in the placebo group, and in PRIME2, 7.7% vs 24.4%, respectively. There were also few instances of treatment-emergent serious adverse events, with just 5 in the dupilumab group but 8 in the placebo group in PRIME and 2 in each group in PRIME2. Most of these AEs were not linked to the study, the exception being mesenteritis and sepsis seen in 1 patients in PRIME’s placebo group. There also were no instances of treatment discontinuation in dupilumab-treated patients.

“Management of prurigo nodularis is challenging, particularly for patients with moderate or severe prurigo nodularis for whom topical therapies are, in many cases, insufficient to control the disease,” the study authors wrote. “These data represent the first replicate positive results from 2 phase 3, randomized, placebo-controlled global trials.”

They concluded that dupilumab led to significant improvement among patients whose prurigo nodularis was inadequately controlled with topical therapies, as well as that the monoclonal antibody’s safety in their trials echoes previous research.

Reference

Yosipovitch G, Mollanazar N, Ständer S, et al. Dupilumab in patients with prurigo nodularis: two randomized, double-blind, placebo-controlled phase 3 trials. Nat Med. 2023;29(5):1180-1190. doi:10.1038/s41591-023-02320-9