Nemolizumab Maintains Long-Term Efficacy in AD

The long-term management of atopic dermatitis (AD) continues to challenge clinicians, particularly in patients with moderate to severe disease where itch, sleep disturbance, and recurrent inflammation persist despite existing biologic and systemic therapies. Although biologics targeting IL-4 and IL-13 signaling, such as dupilumab, lebrikizumab, and tralokinumab, have transformed disease management, they do not provide adequate control in all patients and are sometimes limited by tolerability issues, including ocular surface disease and conjunctivitis. Janus kinase inhibitors offer an oral alternative but carry safety considerations in certain populations. Consequently, new therapeutic options addressing unmet needs, particularly rapid and durable itch relief, remain essential.¹

Background

Nemolizumab, a humanized monoclonal antibody targeting the IL-31 receptor alpha (IL-31RA), acts by interrupting IL-31–mediated neuroimmune signaling that drives pruritus and contributes to skin inflammation and barrier dysfunction. In earlier phase 3 trials (ARCADIA 1 and 2 (NCT03985943 and NCT03989349), nemolizumab demonstrated significant reductions in both skin lesions and itch intensity within 16 weeks compared with placebo. In those studies, “clinically meaningful improvements in itch were observed as early as 1 week after nemolizumab treatment initiation,” emphasizing its potential to address one of the most burdensome symptoms of AD.² Building upon these findings, the ARCADIA long-term extension (LTE) study (NCT03989206) was designed to evaluate the long-term safety and efficacy of nemolizumab in adolescents and adults with moderate to severe AD over a planned 200-week treatment period. The interim analysis, with data through 104 weeks (cut-off July 21, 2024), provides the most extensive safety and durability data for nemolizumab to date.³

Methods and Materials

The ARCADIA LTE is a prospective, multicenter, open-label phase 3 study conducted at 291 sites across 22 countries. Patients were eligible if they completed one of the nemolizumab lead-in trials and met all LTE entry criteria. Participants were categorized based on prior nemolizumab exposure: previously treated patients (PNE) and nemolizumab-naïve entrants (NNE). All patients received subcutaneous nemolizumab 30 mg every four weeks following an initial loading dose of 60 mg for NNE participants. Standard background therapy with topical corticosteroids, with or without topical calcineurin inhibitors, was permitted and could be adjusted at the investigator’s discretion.

Results

A total of 1,903 patients were enrolled, and 1,901 received at least 1 dose of nemolizumab. By the data cut-off, 75.5 percent of participants had completed 56 weeks and 55.9 percent had reached the 104-week visit. The safety profile of nemolizumab remained stable over time. Overall, 79.4 percent of patients experienced at least 1 treatment-emergent adverse event (TEAE), the majority of which were mild or moderate in severity. The most frequently reported TEAEs were COVID-19 (19.6 percent), nasopharyngitis (19.5 percent), atopic dermatitis exacerbation (18.1 percent), upper respiratory tract infection (12.7 percent), headache (6.5 percent), and asthma (5.5 percent). Serious adverse events occurred in 8.1 percent of patients, with only 0.9 percent considered related to study treatment. AEs of special interest, mainly infections and mild peripheral edema, were reported in approximately one-quarter of patients, consistent with earlier trials. Immunogenicity remained low, with anti-drug antibodies detected in 5 percent at week 104 and only 2 patients developing neutralizing antibodies.

Efficacy outcomes demonstrated sustained and progressive improvement in disease activity, itch, sleep, and quality of life across both PNE and NNE cohorts. Investigator Global Assessment (IGA) scores of clear or almost clear (0/1) were achieved in 55.0 percent of previously treated and 53.4 percent of naïve patients by week 56, increasing to 62.6 and 58.2 percent, respectively, by week 104. Eczema Area and Severity Index (EASI-75) responses surpassed 80 percent at week 56 and approached 90 percent by week 104, while mean SCORAD scores declined from approximately 65 at baseline to around 17 after 2 years of treatment. The antipruritic effect was notable and durable: mean visual analogue scale (VAS) pruritus scores improved from 7.3 at lead-in baseline to 1.4 by week 104, with 87.2 percent of PNE and 82.0 percent of NNE patients achieving a 4-point or greater reduction in itch. Sleep loss scores showed parallel improvement, decreasing from 6.2 to 1.3 over the same period. Health-related quality of life, assessed by the Dermatology Life Quality Index (DLQI), improved rapidly and was sustained throughout the two-year observation window. Patient global assessments of disease and treatment satisfaction also demonstrated consistent upward trends over time.

Pharmacokinetic assessments revealed stable serum nemolizumab concentrations from week 20 through week 104, maintaining steady-state conditions throughout long-term treatment. The study authors noted that “patients continue to improve beyond the week 16 primary outcome timepoint used in phase 3 studies, and a high level of skin clearance is achieved with long-term treatment.” This ongoing improvement underscores the chronic, cumulative nature of therapeutic benefit in AD and suggests that nemolizumab efficacy may continue to build with sustained use.

Conclusion

Overall, the ARCADIA LTE data reinforce nemolizumab’s role as a safe and effective long-term therapy for moderate to severe AD. No new safety signals were identified, and the tolerability profile remained consistent across 2 years of exposure. Importantly, nemolizumab has not been associated with ocular surface disease, a notable distinction from IL-4/IL-13–targeting biologics. For clinicians, these findings highlight nemolizumab as a viable option for patients requiring durable itch relief, long-term skin control, and an alternative mechanism of action. While open-label design and concomitant topical use represent study limitations, the consistent trends across multiple endpoints and patient subgroups support the robustness of the findings. The 104-week interim results confirm nemolizumab as a promising addition to the AD therapeutic armamentarium, providing sustained symptom control, improved quality of life, and a reassuring long-term safety profile for both adolescent and adult patients.

References

1. Müller S, Maintz L, Bieber T. Treatment of atopic dermatitis: Recently approved drugs and advanced clinical development programs. Allergy. 2024;79(6):1501-1515. doi:10.1111/all.16009

2. Silverberg JI, Wollenberg A, Reich A, et al. Nemolizumab with concomitant topical therapy in adolescents and adults with moderate-to-severe atopic dermatitis (ARCADIA 1 and ARCADIA 2): results from two replicate, double-blind, randomised controlled phase 3 trials. Lancet. 2024;404(10451):445-460. doi:10.1016/S0140-6736(24)01203-0

3. Augustin M, Tauber M, Sidbury R, et al. Safety and efficacy of nemolizumab for atopic dermatitis up to 2 years in open-label extension study. J Eur Acad Dermatol Venereol. Published online October 13, 2025. doi:10.1111/jdv.70080