Nemolizumab Improves Pruritis, Sleep Within 2 Days When Added to Standard Topical Therapy for Atopic Dermatitis

Nemolizumab, an interleukin-31 (IL-31) alpha antagonist, demonstrated rapid onset of efficacy for pruritus and sleep disturbance in patients with moderate-to-severe atopic dermatitis, according to results from 2 pivotal phase 3 clinical trials. The ARCADIA 1 and ARCADIA 2 studies showed statistically significant improvements in both symptoms within 1 or 2 days of treatment initiation when nemolizumab was added to topical corticosteroids with or without topical calcineurin inhibitors. Results of the study, which was led by Jonathan Silverberg, MD, PhD, MPH, associate professor of dermatology at the George Washington University School of Medicine and Health Sciences, in Washington, DC, were presented as a poster at the Revolutionizing Atopic Dermatitis meeting, June 6-7, 2025 in Nashville, TN.

Jonathan Silverberg, MD, PhD, MPH

Nemolizumab targets the IL-31 pathway, which mediates both pruritus and inflammation in atopic dermatitis. Previous studies established the IL-31 inhibitor's efficacy and safety profile through 48 weeks of treatment, with sustained improvements in pruritus, skin lesions, and sleep quality maintained at Week 16 and Week 48 endpoints. The current study specifically assessed the speed of onset of itch and sleep response with the addition of nemolizumab.

The ARCADIA studies were identical, randomized, placebo-controlled tirals conducted across multiple international sites. Participants aged 12 years and older with moderate-to-severe atopic dermatitis received either 30 mg nemolizumab or placebo every 4 weeks in addition to standard topical therapy, with randomization occurring in a 2:1 ratio favoring active treatment.

In ARCADIA 1, participants treated with nemolizumab showed significantly greater least squares mean change from baseline in Peak Pruritus Numerical Rating Scale (PP NRS) scores by day 1 compared to those receiving placebo (-0.9±0.06 vs -0.5±0.08, P <.001). Similar early efficacy was seen in ARCADIA 2, with nemolizumab-treated participants experiencing greater pruritus reduction (-1.1±0.07 vs -0.4±0.10, P <.001) within 24 hours.

Responder analyses using the clinically meaningful threshold of ≥4-point improvement in PP NRS revealed that 9.4% of nemolizumab patients in ARCADIA 1 achieved this endpoint by day 2, compared to 3.4% of placebo recipients (P <.001). In ARCADIA 2, 8.2% of treated patients reached this threshold by Day 1, versus 1.9% of placebo patients (P <.001).

Silverberg et al reported that sleep outcomes measured by the Sleep Disturbance Numerical Rating Scale mirrored improvements in pruritis. In ARCADIA 1, 8.7% of nemolizumab-group participants achieved ≥4-point improvement by day 2 compared to 4.0% of placebo-treated participants (P <.001). In ARCADIA 2, 10.0% of treated patients reached this endpoint by day 1 versus 2.6% of placebo recipients (P <.001).

The research team concluded that nemolizumab plus topical corticosteroids with or without topical calcineurin inhibitors produces rapid, statistically significant, and clinically meaningful improvements in pruritus and sleep disturbance within two days in patients with moderate-to-severe atopic dermatitis. This rapid onset addresses the clinical need for faster symptom relief in this patient population, where pruritus significantly impacts quality of life and sleep quality.

The findings contribute to the growing evidence base for IL-31 pathway inhibition in atopic dermatitis treatment, particularly regarding the temporal relationship between treatment initiation and symptom improvement. The consistent results across both pivotal studies support the reproducibility of the rapid efficacy profile observed with nemolizumab therapy.

Jonathan I Silverberg¹, Linda Stein-Gold²,Diamant Thaçi³, Andrew E Pink^4,5, Kim A Papp^6,7,Franz J Legat⁸, Vivian T Laquer⁹, Soo Yeon Cheong¹⁰, Liliana Ulianov¹¹, Anna Ryzhkova¹¹, Christophe Piketty¹¹