Nemolizumab Rapidly Relieves Itch in Atopic Dermatitis, Prurigo Nodularis

A new post-hoc analysis has confirmed previous data suggesting nemolizumab relieves itch and sleep disturbances by the second day of use in those with moderate-to-severe atopic dermatitis and prurigo nodularis.1

These findings, pointing to the potential of targeting the interleukin (IL)-31 pathway for these dermatologic disease, were authored by such investigators as Sonja Ständer, MD. Previous findings on these 2 disease states led to positive results for patients on nemolizumab, Ständer et al highlighted.

“Previous data from phase 2 studies with nemolizumab demonstrated rapid itch relief in patients with AD and PN,” Ständer and colleagues noted.1,2,3 “This post hoc study analysed the pivotal phase 3 clinical trial dataset to confirm the early onset of itch responses with nemolizumab.

Design and Findings

The investigative team conducted their post hoc assessment of 4 multinational, large randomized controlled trials: ARCADIA 1 and ARCADIA 2 for patients with atopic dermatitis and OLYMPIA 1 and OLYMPIA 2 for patients with prurigo nodularis. The team pointed to the identical design of ARCADIA 1 and 2 as double-blind, placebo-controlled analyses lasting 48 weeks and involving adult participants alongside adolescents aged 12 years and older with moderate-to-severe atopic dermatitis, a Peak Pruritus Numerical Rating Scale (PP-NRS) score of at least 4 (suggesting significant pruritus), and an insufficient response to the use of topical corticosteroids.

In the OLYMPIA 1 and OLYMPIA 2 studies, patients were enrolled who were adults and living with moderate-to-severe prurigo nodularis. Additionally, these participants would have severe itch, characterized by a baseline PP-NRS score of 7 at minimum. While both OLYMPIA studies mainained the same overall design, Ständer and coauthors noted the differences between durations of nemolizumab use, with the course being 24 weeks in OLYMPIA 1 and only 16 weeks in OLYMPIA 2. Within the ARCADIA studies, those involved were given nemolizumab 30 mg every 4 weeks, preceded by a 60 mg loading dose, or a matching placebo, along with a topical background treatment.

The investigators noted, for OLYMPIA 1 and 2, dosing of the medication was weight based, with individuals weighing less than 90 kg being treated with 30 mg every 4 weeks with a 60 mg loading dose. Meanwhile, those weighing 90 kg or more were given 60 mg on an every-4-week basis and subjects who were placebo-treated received corresponding placebo injections. Across all 4 of the pivotal trials, a clinically meaningful reduction in itch was defined by the investigative teams as at least a 4-point improvement from baseline in subjects' weekly average PP-NRS scores.

During the ARCADIA 1 and 2 analyses, the investigators' co-primary endpoints were Investigator’s Global Assessment (IGA) success and, from baseline, at least a 75% Eczema Area and Severity Index (EASI) score reduction by the 16-week mark. A ≥4-point improvement observed in participants' weekly average PP-NRS was a key secondary endpoint. In OLYMPIA 1 and 2, the investigators' primary endpoints at the 16-week mark were itch response, also described by Ständer and colleagues as a ≥4-point reduction in subjects' weekly average PP-NRS, and IGA success.

A reduction of Sleep Disturbance Numerical Rating Scale (SD-NRS) scores by at least 4 points was determined to be a key secondary endpoint in all studies. The PP-NRS, as a validated patient-reported measure worst itch over the preceding 24 hours, was recorded daily from baseline through Week 16 in all of the 4 analyses. Assessments extended to the 24-week mark in those living with prurigo nodularis. Sleep disturbance was measured using a 4-point improvement on the SD-NRS. For the purposes of this post hoc analysis, PP-NRS and SD-NRS responders were defined by Ständer and coauthors as individuals attaining a reduction of at least 4 points from baseline in daily scores. They defined baseline as the last non-missing evaluation prior to patients' first nemolizumab dose.

The investigative team of the post hoc analysis compared responder proportions for sleep as well as itch outcomes between treatment groups on a daily basis over the first 14 days in each individual study. Data drawn from ARCADIA 1 and 2 were pooled and then data from OLYMPIA 1 and 2 were pooled. All of the assessments were performed by the team for the intention-to-treat population, which included all randomized patients.

Overall, Ständer et al found nemolizumab resulted in a rapid onset of itch relief in patients with atopic dermatitis. The pooled ARCADIA data they evaluated demonstrated a separation from placebo by the second day, when 10.7% of nemolizumab-treated patients were PP-NRS responders as opposed to 2.9% of subjects on placebo (95% CI, 5.6–10.1; P < .0001). Response rates went on to increase through Day 14.

The team highlighted a similarly early effect observed in subjects with prurigo nodularis. Specifically, their pooled OLYMPIA data demonstrated PP-NRS response rates of 17.2% with the medication versus 3.7% with placebo by the second day (95% CI, 6.8–16.7; P < .0001). Sleep disturbance problems were also shown to improve as early as Day 2 among individuals on nemolizumab. Ständer and colleagues' pooled analyses of the atopic dermatitis trials showed 9.9% of those on the drug were SD-NRS responders compared with 4.6% in on the placebo (95% CI, 2.8–7.7; P = .0001).

Their pooled prurigo nodularis data indicated corresponding response rates were 13.4% with the medication and 4.3% with placebo (95% CI, 4.0–13.0; P = .0013). Overall, these results from the individual trials were consistent with Ständer and coauthors' pooled results for both itch and sleep outcomes.

“Nemolizumab, a drug with a novel mechanism of action, has a rapid onset of action on itch associated with improvements in sleep disturbance; together, these outcomes may contribute to better quality of life for patients with [atopic dermatitis and prurigo nodularis],” Ständer et al concluded.1

References

1. Ständer S, Elmariah SB, Cheong SY, et al. Rapid improvement of itch with nemolizumab in atopic dermatitis and prurigo nodularis phase 3 studies. J Eur Acad Dermatol Venereol. 2025; 00: 1–9. https://doi.org/10.1111/jdv.70250.

2. Silverberg JI, Pinter A, Piketty C, et al. Nemolizumab is associated with a rapid improvement in atopic dermatitis signs and symptoms: subpopulation (EASI ≥ 16) analysis of randomized phase 2B study. J Eur Acad Dermatol Venereol. 2021 Jul;35(7):1562-1568. doi: 10.1111/jdv.17218. Epub 2021 Apr 1. PMID: 33711179.

3. Ständer S, Yosipovitch G, Piketty C, et al. Nemolizumab efficacy in prurigo nodularis: onset of action on itch and sleep disturbances. J Eur Acad Dermatol Venereol. 2022 Oct;36(10):1820-1825. doi: 10.1111/jdv.18377. Epub 2022 Jul 4. PMID: 35766128; PMCID: PMC9796585.