Safety and efficacy of nemolizumab for atopic dermatitis up to 2 years in open‐label extension study

Abstract

Background

Atopic dermatitis (AD) is a common, chronic, relapsing, pruritic, neuroimmune skin disease, requiring long‐term symptom control.

Objectives

The ARCADIA long‐term extension (LTE) study evaluates nemolizumab safety and efficacy in ≥12‐year‐old patients with moderate‐to‐severe AD up to 200 weeks.

Methods

Patients from previous nemolizumab AD trials (Phase 2/3) or newly recruited adolescents with moderate‐to‐severe AD were enrolled. A background regimen of topical corticosteroids with/without topical calcineurin inhibitors was permitted based on disease control. Long‐term safety was the primary endpoint. Efficacy assessments were secondary endpoints, including the proportion of patients achieving Investigator's Global Assessment (IGA) 0/1 (clear/almost clear), Eczema Area and Severity Index (EASI)‐75 (75% improvement from lead‐in baseline in EASI), Visual Analogue Scale (VAS) Pruritus and VAS sleep loss ≥4‐point improvement from lead‐in baseline and quality of life. Observed data up to Week (W) 104 are presented for patients with previous nemolizumab experience (PNE) and no previous nemolizumab experience (NNE) at LTE baseline.

Results

At interim analysis data cut‐off (21 July 2024), 1062 of 1901 patients completed W104. Exposure to nemolizumab in this study was equal across cohorts. The majority (92.6%) of treatment‐emergent adverse events (TEAEs) were mild/moderate in severity; only 22.1% were considered related to nemolizumab. The most common (≥5.0%) TEAEs were COVID‐19 (19.6%), nasopharyngitis (19.5%), atopic dermatitis (18.1%), upper respiratory tract infection (12.7%), headache (6.5%) and asthma (5.5%). At LTE baseline, the proportion of PNE and NNE patients was IGA 0/1: 27.1% and 17.1%; EASI‐75: 38.8% and 25.8%; VAS Pruritus ≥4‐point improvement: 58.7% and 31.6%; and VAS sleep loss ≥4‐point improvement: 52.9% and 31.6%, respectively. At W104, this proportion was IGA 0/1: 62.6% and 58.2%; EASI‐75: 88.2% and 85.4%; VAS Pruritus ≥4‐point improvement: 87.2% and 82.0%; and VAS sleep loss ≥4‐point improvement: 70.8% and 68.9%, respectively.

Conclusions

Continuous nemolizumab treatment was well‐tolerated through W104 with clinically meaningful improvements in AD signs and symptoms and patient‐reported outcomes.

Trial Registration

NCT03989206: https://clinicaltrials.gov/search?term=NCT03989206; EUDRACT number: 2019–001889‐15. Data available upon request: clinical.studies@galderma.com.

Plain Language Summary

Atopic dermatitis, also known as eczema, is a common long‐lasting condition that causes itchy, inflamed and irritated skin. It often comes and goes and can have a big impact on well‐being with severe itch, skin pain, sleep deprivation, anxiety and depression.

The world‐wide ARCADIA long‐term extension study followed 1901 patients with atopic dermatitis aged 12 years and older for up to 2 years to learn if nemolizumab, a medicine that stops itching and skin inflammation, was safe to use and improved atopic dermatitis and patient well‐being.

Patients in the study received nemolizumab injections every 4 weeks, along with other skin creams or ointments. The study included patients who had never used nemolizumab before, and patients who had used nemolizumab in earlier studies.

The researchers found that common adverse effects included cold‐like symptoms, worsening of atopic dermatitis, headaches and worsening of asthma. Most adverse effects were mild or moderate. 75% of adverse effects were unrelated to treatment with nemolizumab.

After 2 years of treatment with nemolizumab, around 60% of patients had skin that was clear or almost clear of atopic dermatitis, and over 85% of patients had less severe atopic dermatitis. Over 80% of patients felt less itchy. Around 70% of patients slept better, and over 90% of patients said that atopic dermatitis had no or minimal impact on their well‐being.

Nemolizumab appears to be a safe and effective long‐term treatment for atopic dermatitis. It can help clear the skin, reduce itching and improve sleep and well‐being.

This study evaluated long‐term safety and efficacy in patients with moderate‐to‐severe atopic dermatitis. Patients with and without previous nemolizumab experience received nemolizumab 30 mg Q4W plus TCS/TCI. Nemolizumab was well‐tolerated through 104 weeks with clinically meaningful improvements in disease signs and symptoms. Most TEAEs were mild/moderate and not related to nemolizumab.

Why was the study undertaken?

The aim of this study was to evaluate the long‐term safety and efficacy of nemolizumab in adolescents and adults with moderate‐to‐severe atopic dermatitis (AD) in a 104‐week interim analysis of the 200‐week ARCADIA open‐label long‐term extension (LTE) study.

What does this study add?

Nemolizumab with background topical corticosteroids with/without topical calcineurin inhibitors improved key aspects of AD: Pruritus, skin lesions and sleep disturbance, and provided relevant treatment benefits for patients long term. The majority of treatment‐emergent adverse events were mild or moderate.

What are the implications of this study for disease understanding and/or clinical care?

The ARCADIA LTE study supports the safety and efficacy of long‐term nemolizumab for adolescent/adult patients with moderate‐to‐severe AD. Currently available biologic agents are effective in patients with AD and have demonstrated comparable long‐term efficacy in a similar proportion of patients.

INTRODUCTION

Atopic dermatitis (AD) is a common, chronic, relapsing inflammatory skin disease characterized by pruritic and painful eczematous lesions, which can present as heterogeneous clinical phenotypes and requires long‐term disease control. ¹ , ² AD often starts in childhood with a prevalence of up to 20%, ³ and may persist into adulthood, ⁴ , ⁵ affecting up to 7% of adults. ⁶ Persistence is greater with later onset and more severe disease. ⁵

AD is a debilitating disease with intense, persistent, symptomatic eczematous lesions impacting sleep and quality of life (QoL), ⁷ , ⁸ , ⁹ affecting psychological well‐being and potentially resulting in depression and suicidal ideation ⁹ , ¹⁰ and other mental health comorbidities. ¹¹ , ¹² , ¹³ AD can be associated with higher rates of infections, particularly skin infections, other atopic diseases, hypertension, hypercholesterolemia, diabetes and obesity. ¹⁴

AD can be a lifelong disease, therefore well‐tolerated and effective treatments are needed for long‐term control, skin healing and itch relief. ¹ While topical agents may offer temporary itch relief in mild AD, their effectiveness in treating severe, persistent itch is limited. ¹⁵ Many AD treatments may not be administered long‐term due to safety concerns, or lack of efficacy data. ¹⁶

Among currently available biologics, dupilumab, ¹⁷ lebrikizumab, ¹⁸ , ¹⁹ and tralokinumab ²⁰ target interleukin (IL)‐4 and/or IL‐13 pathways. While effective in treating AD, these biologics do not provide sufficient disease control for every patient and pose tolerability concerns including conjunctivitis, ²¹ , ²² , ²³ herpes ²¹ , ²³ and arthralgia. ²¹ Janus kinase inhibitors (JAKI) are alternative oral treatment options for AD, but carry a risk for adverse events (AEs) in certain patient groups. ²⁴ As itch relief is the most frequently named patient need, new treatment options with an alternative mode of action for patients with moderate‐to‐severe AD are required to provide fast itch relief paired with long‐term control and tolerability for long‐term use. ²⁵ , ²⁶ , ²⁷

IL‐31 is a key neuroimmune cytokine in the pathophysiology of AD, driving itch and contributing to inflammation and skin barrier disruption. ²⁸ , ²⁹ IL‐31 signals through a heterodimeric receptor alpha (IL‐31RA)/oncostatin M receptor beta (OSMRβ). ³⁰ , ³¹ Nemolizumab, a recently approved biologic for treatment of moderate‐to‐severe AD in patients ≥12 years, is a humanized monoclonal antibody that blocks IL‐31 signalling by binding to the IL‐31RA with high specificity and affinity. ³²

Nemolizumab demonstrated rapid improvement in skin lesions and itch with a favourable safety profile in Phase 2b (NCT03100344) ³² , ³³ and Phase 3 ARCADIA 1 (NCT03985943) and ARCADIA 2 (NCT03989349) ³⁴ clinical trials in patients with moderate to severe AD.

Objective

The aim of the ARCADIA long‐term extension (LTE) study (NCT03989206) was to evaluate long‐term safety (primary endpoint) and efficacy in itch and skin (secondary endpoints) of nemolizumab administered concomitantly with a background regimen of topical corticosteroids with or without topical calcineurin inhibitors in adolescents and adults with moderate‐to‐severe AD. Data are from the interim analysis through 104 weeks (data cut‐off 21 July 2024).

METHODS

Study design, patients and treatment

The ARCADIA LTE is an ongoing, prospective, multicentre, open‐label, Phase 3 study at 291 sites in 22 countries from December 2019. The study included up to a 4‐week screening period, a 200‐week treatment period and an 8‐week follow‐up period (Figure 1). Patients had to complete all required visits in the lead‐in study and fulfill other eligibility criteria prior to LTE participation. An Independent Data Monitoring Committee (IDMC) reviewed and monitored patient safety throughout the study.

FIGURE 1.

Study design. Patients from seven Phase 2 and 3 studies and newly recruited adolescents who entered the LTE. AD, atopic dermatitis; PK, pharmacokinetic; SC, subcutaneous; TCS, topical corticosteroids; TCI, topical calcineurin inhibitors. ^aAdolescents who did not participate in any previous nemolizumab study but satisfied eligibility criteria, such as chronic AD for ≥2 years, Eczema Area and Severity Index (EASI) score ≥16, Investigator's Global Assessment (IGA) score ≥3, AD involvement ≥10% of body surface area and SCORing Atopic Dermatitis (SCORAD) pruritus VAS score ≥4. ^bThe ‘N’ values indicated for each lead‐in study are those at the data cut‐off date. ^cAt baseline, patients received either nemolizumab 60 or 30 mg plus placebo depending on treatment received (nemolizumab or placebo) in the lead‐in study and interval (≥12 weeks/<12 weeks) between the last dose in the lead‐in study and baseline dose in the LTE study. For ARCADIA 1, ARCADIA 2, Phase 2 vaccination safety study and phase 3b study, a blinded loading dose was administered as assigned by interactive response technology from the lead‐in study. Newly recruited adolescents, patients from Phase 2b dose‐ranging study, Phase 2 adolescent PK/safety study and Phase 2 drug–drug interaction were given the open‐label loading dose of nemolizumab. ^dBackground topical therapy with low/medium potency TCS or TCI were used in new adolescents within the screening period and ≥14 days before Day 1; for other patients it was continued as prescribed by the investigator immediately before enrolling in the LTE study. ^eBlinded lead‐in study patients, that is patients who rolled over from ongoing blinded study maintained the blind and were not included in the two study cohorts.

Patients either had previous nemolizumab experience (PNE; in the lead‐in studies, regardless of the duration of treatment or interval between the last dose in the lead‐in studies and baseline dose in the LTE) or no previous nemolizumab experience (NNE; patients who received placebo in the lead‐in studies, or newly enrolled adolescents). Patients with PNE in lead‐in studies within 12 weeks of their last study drug injection received a single dose of 30 mg subcutaneous (SC) nemolizumab and one placebo injection at the LTE baseline. All other patients received a loading dose of 60 mg nemolizumab (two SC injections) at the LTE baseline. At subsequent visits, all patients received 30 mg nemolizumab, Q4W.

Background therapy with topical corticosteroids with or without topical calcineurin inhibitors was allowed in the LTE study and could be tapered down as per the treating physician's decision according to disease activity and tolerability, including tapering when signs and symptoms improve, discontinuation when lesions clear and restarting if signs and symptoms recur (Table S1). Patient disposition is shown in Figure 2.

FIGURE 2.

Patient disposition (interim data summary). EASI, Eczema Area and Severity Index; IGA, Investigator's Global Assessment; Q4W, every 4 weeks; Q8W, every 8 weeks.

Study endpoints and assessments

Primary endpoints and assessments: Long‐term safety

Safety endpoints included the incidence and severity of treatment‐emergent AEs (TEAEs), serious AEs (SAEs) and the incidence and severity of AEs of special interest (AESIs). An Independent Adjudication Committee reviewed all asthma‐related events until protocol V12.0 approval. Assessments of vital signs, physical examinations, electrocardiogram recording, AEs, respiratory assessments and clinical laboratory results (routine haematology, biochemistry and urinalysis) were performed throughout the study (respiratory assessments and urinalysis until protocol V12.0 approval).

Secondary endpoints and assessments: Long‐term efficacy

Efficacy assessments at each visit included the proportion of patients with IGA score 0/1 (clear/almost clear), proportion of patients with 50/75/90% improvement in EASI score from lead‐in baseline, change from lead‐in baseline in SCORAD score, SCORAD VAS Pruritus (change from lead‐in baseline, proportion of patients with ≥4 improvement from lead‐in baseline; score <2), SCORAD VAS sleep loss (change from lead‐in baseline, proportion of patients with ≥4 improvement from lead‐in baseline), proportion of patients with ≥4‐point reduction from lead‐in baseline in Dermatology Life Quality Index (DLQI) total score and DLQI score 0/1, proportion of patients reporting low disease activity state (clear, almost clear or mild) based on Patient Global Assessment of Disease (PGAD) 5‐point scale and proportion of patients satisfied with study treatment (good, very good or excellent) based on Patient Global Assessment of Treatment (PGAT) 5‐point Likert scale. Efficacy endpoints are described in Table S2.

Additional endpoints

The pharmacokinetic endpoint was nemolizumab trough serum concentrations. The immunogenicity endpoint was the formation of anti‐drug antibody (ADA), the ADA potency (titre) and the formation of neutralizing antibody.

Statistical analyses

The LTE baseline was defined as the last non‐missing value prior to the date of first treatment in the LTE study. The lead‐in study baseline was defined as the last non‐missing value before the first dose of study drug of the lead‐in studies (for patients whose interval between the LTE baseline and the date of last study drug administration in the lead‐in study was ≤6 months). Statistical analyses were performed on the safety population, defined as all patients who received at least 1 dose of study drug. Observed case (OC) data were used to summarize all efficacy and safety endpoints.

Sensitivity analyses were performed using multiple imputation (MI) under the missing at random (MAR) assumption up to Week 56 for the selected efficacy endpoints IGA, EASI, SCORAD, VAS Pruritus and VAS Sleep loss (Tables S2 and S3). All efficacy data on or after the use of rescue therapy were treated as treatment failure before the MI. The fifty (50) imputed datasets with a monotone missing pattern were generated with Markov chain Monte Carlo (MCMC) methodology for the data with a non‐monotone missing pattern. Using a linear or logistic regression, the imputation of each dataset was completed up to Week 56, and the response or total score of the endpoints was derived using the imputed datasets. The results of each dataset were combined using Rubin's rule.

RESULTS

Patients

Interim analysis was conducted on all efficacy and safety data available at the data cut‐off (21 July 2024), including 1903 enrolled patients of whom 1901 were treated. A total of 1436 of 1901 (75.5%) patients had completed Week 56 visit and 1062 of 1901 patients had completed Week 104 visit at data cut‐off. Efficacy results up to Week 104 are presented as sample sizes beyond which were too small to make meaningful interpretations. Patient disposition is shown in Figure 2. Exposure to nemolizumab in this study was equal across cohorts.

Demographic and baseline characteristics (Table 1) were generally similar by previous treatment, with some variability for disease severity. Medical histories and previous and concomitant medications and procedures were as expected for this patient population.

TABLE 1.

Demographic and baseline characteristics by previous treatment.

	Previous nemolizumab experience (N = 1164)	No previous nemolizumab experience (N = 737)	Total study population (N = 1901)
Age (years), mean (SD)	34.4 (15.8)	33.3 (15.1)	34.0 (15.6)
Median (range, min–max)	31.0 (12–85)	30.0 (12–84)	30.0 (12–85)
Age group, n (%) 12–17 years	142 (12.2)	112 (15.2)	254 (13.4)
Male, n (%)	578 (49.7)	385 (52.2)	963 (50.7)
Ethnicity, n (%)
Hispanic or Latino	107 (9.2)	66 (9.0)	173 (9.1)
Not Hispanic or Latino	1043 (89.6)	667 (90.5)	1710 (90.0)
Not reported	8 (0.7)	3 (0.4)	11 (0.6)
Unknown	6 (0.5)	1 (0.1)	7 (0.4)
Race, n (%)
White	942 (80.9)	583 (79.1)	1525 (80.2)
Black or African American	63 (5.4)	51 (6.9)	114 (6.0)
Asian	143 (12.3)	86 (11.7)	229 (12.0)
Other a	16 (1.4)	17 (2.3)	33 (1.7)
Body weight (kg), mean (SD)	75.6 (18.2)	76.0 (19.4)	75.8 (18.6)
BMI (kg/m2) b , mean (SD)	n = 1126, 26.1 (5.6)	n = 712, 26.1 (6.0)	n = 1838, 26.1 (5.8)
EASI score, mean (SD)	n = 1161, 11.9 (11.7)	n = 735, 15.6 (12.5)	n = 1896, 13.3 (12.1)
IGA score, n (%)
0: Clear	116 (10.0)	47 (6.4)	163 (8.6)
1: Almost clear	199 (17.1)	79 (10.7)	278 (14.6)
2: Mild	337 (29.0)	190 (25.8)	527 (27.7)
3: Moderate	426 (36.6)	340 (46.1)	766 (40.3)
4: Severe	85 (7.3)	81 (11.0)	166 (8.7)
Not reported	1 (0.1)	0	1 (0.1)
SCORAD, mean (SD)	n = 1122, 35.26 (20.1)	n = 707, 44.07 (20.7)	n = 1829, 38.66 (20.8)
BSA c (%) of AD Involvement, mean (SD)	24.3 (22.3)	28.1 (22.3)	25.8 (22.4)
DLQI, mean (SD) Patients ≥17 years old	n = 993, 6.8 (6.6)	n = 617, 9.3 (7.3)	n = 1610, 7.7 (7.0)
cDLQI, mean (SD) Patients 12–16 years old	n = 113, 5.4 (5.8)	n = 83, 9.0 (6.0)	n = 196, 6.9 (6.1)

Note: Baseline was the last available measurement prior to the first treatment in this study. Patients with previous nemolizumab experience were treated with nemolizumab at least once before the LTE study. Patients with no previous nemolizumab experience were never exposed to nemolizumab before the LTE study. Percentage (%) was calculated using N as the denominator.

Abbreviations: AD, atopic dermatitis; BMI, body mass index; BSA, body surface area; cDLQI, children's Dermatology Life Quality Index; DLQI, Dermatology Life Quality Index; EASI, Eczema Area and Severity Index; IGA, Investigator's Global Assessment; LTE, long‐term extension; N, total number of patients; n, number of patients with available data; SCORAD, Scoring Atopic Dermatitis; SD, standard deviation.

^a Other races included American Indian or Alaska Native, Native Hawaiian or Other Pacific Islander, Other races and patients of multiple races.

^b BMI (kg/m²) was calculated using height and weight at baseline.

^c BSA data were not collected following protocol amendment (v12).

Safety endpoints

TEAEs

A total of 1510 (79.4%) patients experienced at least 1 TEAE during the Treatment Period (Table 2); the majority were mild (28.1%) or moderate (44.0%) in severity. Exposure‐adjusted incidence rate (EAIR; events per hundred patient years) was 114.4 for any TEAE. Study drug‐related TEAEs were experienced by 421 (22.1%) patients during the Treatment Period (Table 2). The most common (≥5.0%) TEAEs were COVID‐19 (19.6%), nasopharyngitis (19.5%), dermatitis atopic (nomenclature from the Medical Dictionary for Regulatory Activities; 18.1%), upper respiratory tract infection (12.7%), headache (6.5%) and asthma (5.5%).

TABLE 2.

Overall summary of treatment‐emergent adverse events (TEAEs) during the treatment period.

	Total study population (N = 1901) n (%)	EAIR/100 person year	EAER/100 person year
AEs or SAEs
Any TEAE	1510 (79.4)	114.4	205.4
Any TEAE related to study drug	421 (22.1)	12.7	26.9
Any serious TEAE	154 (8.1)	4.1	5.0
Any serious TEAE related to study drug	17 (0.9)	0.4	0.5
Any severe TEAE	140 (7.4)	3.7	5.1
Any TEAE leading to temporary discontinuation of study drug	261 (13.7)	7.3	9.5
Any TEAE leading to permanent discontinuation of study drug	90 (4.7)	2.3	2.7
Any TEAE leading to permanent discontinuation from study	88 (4.6)	2.2	2.6
Any TEAE leading to death	0	0	0
AESI a
Infections	473 (24.9)	15.1	15.0
Peripheral oedema: limbs, bilateral; facial oedema	34 (1.8)	0.9	1.3
Injection‐related reactions b	2 (0.1)	0.1	0.1
TEAEs with overall incidence ≥5% (MedDRA preferred term)
COVID‐19	372 (19.6)	11.3	11.4
Nasopharyngitis	370 (19.5)	10.9	19.8
Upper respiratory tract infection	241 (12.7)	6.7	9.7
Headache	123 (6.5)	3.3	5.4
Asthma	105 (5.5)	2.8	3.7
Dermatitis atopic	344 (18.1)	9.8	13.8

Note: Data presented are for the safety population up to interim data cut‐off date (21 July 2024). Adverse events were coded using MedDRA version 25.0. Percentage (%) was calculated using N as the denominator. Treatment period was defined as the period from the start of treatment up to Week 200. For patients who discontinued early, it was defined as the period from the start of treatment until 4 weeks after the date of last dose or early termination date, whichever was earlier.

Abbreviations: AE, adverse event; AESI, adverse event of special interest; ALT, alanine transaminase; AST, aspartate aminotransferase; COVID‐19, coronavirus disease 2019; EAER, exposure‐adjusted event rate; EAIR, exposure‐adjusted incidence rate; MedDRA, Medical Dictionary for Regulatory Activities; N, total number of patients; n, number of patients who experienced the events; SAE, serious adverse event; TEAE, treatment‐emergent adverse event; ULN, upper limit of normal.

^a Injection‐related reactions (IRR) and infections were considered AESIs and monitored closely throughout. AEs considered AESIs up to approval of protocol v12.0 were COVID‐19 infections, newly diagnosed asthma or worsening of asthma, peripheral oedema (limbs, bilateral), facial oedema, elevated ALT or AST (>3 × ULN) in combination with elevated bilirubin (>2 × ULN). AEs considered AESIs since approval of protocol v12.0 were eczematous signs (oedematous erythema or scaling, distinct from the exacerbation of the primary disease). After recent protocol amendment approval, newly diagnosed asthma or worsening of asthma, any confirmed or suspected COVID‐19 infection, previously part of AESI ‘Infections’ and elevated ALT or AST (>3 × ULN) in combination with elevated bilirubin (>2 × ULN) are no longer considered for enhanced reporting as AESI.

^b Injection‐related reactions include anaphylactic reactions, acute allergic reactions requiring treatment and severe injection site reactions with a duration >24 h.

Serious TEAEs

No patient died during the treatment period of the study. One patient died during the follow‐up period due to asphyxia; this was unrelated to study drug treatment. During the treatment period, treatment‐emergent SAEs were experienced by 154 (8.1%) patients (Table 2), and 17 (0.9%) patients experienced SAEs considered study drug‐related. The following were reported by one patient (0.1%) each: dyspepsia, appendicitis, infected dermatitis, intestinal perforate diverticulitis, eczema herpeticum, erysipelas, Escherichia sepsis, eye infection, wound abscess, rectal adenocarcinoma, oculomotor nerve paralysis, syncope, chronic glomerulonephritis and spontaneous pneumothorax. In addition, each of the following were reported by two patients (0.1%) each: asthma and AD. The majority of study drug‐related SAEs experienced during the study resolved by data cut‐off.

AESIs

AESIs experienced by patients during the Treatment Period are shown in Table 2. Two (0.1%) PNE patients experienced three incidences of moderate IRRs (as per‐protocol definition) during the treatment period. The events were considered study drug‐related, moderate in severity and resulted in study drug withdrawal and study discontinuation. The following events also led to study drug withdrawal or study discontinuation: newly diagnosed asthma or worsening of asthma (n = 2), infections (n = 2) and peripheral oedema: limbs, bilateral / facial oedema (n = 5 [6 events]).

A total of 473 (24.9%) patients experienced AESIs of infection (Table 2). Most study drug‐related AESIs of infection were non‐serious, mild or moderate in severity, and did not result in study drug withdrawal or study discontinuation.

Thirty‐four (1.8%) patients experienced AESIs of peripheral oedema ([limbs, bilateral] and/or facial oedema) during the treatment period (Table 2). All study drug‐related AESIs of peripheral oedema were non‐serious and considered mild or moderate in severity; one‐half of patients who experienced study drug‐related AESIs of peripheral oedema had events that led to study drug withdrawal and study discontinuation.

The most frequently reported TEAEs of clinical interest were infections, including herpes infection (Table 3).

TABLE 3.

TEAEs of clinical interest as exposure‐adjusted incidence and event rates per 100 person‐year during the treatment period.

TEAEs of clinical interest	Total study population (N = 1901), n (%)	EAIR/100 person year	EAER/100 person year
Sinusitis	62 (3.3)	1.6	2.0
Urinary tract infection	65 (3.4)	1.7	2.0
Arthralgia	57 (3.0)	1.5	1.8
Conjunctivitis	39 (2.1)	1.0	1.2
Conjunctivitis allergic	33 (1.7)	0.9	0.9
Herpes	119 (6.3)	3.1	4.5

Note: Percentage (%) was calculated using N as the denominator.

Abbreviations: EAER, exposure‐adjusted event rate; EAIR, exposure‐adjusted incidence rate; MedDRA, Medical Dictionary for Regulatory Activities; N, total number of patients; n, number of patients who experienced the events; TEAE, treatment‐emergent adverse event; herpes included: oral herpes, herpes simplex, herpes zoster, herpes dermatitis, herpes virus infection, herpes ophthalmic, ophthalmic herpes simplex.

Discontinuation

Rates of discontinuation from the study were similar between PNE patients and those who were NNE. Reasons for discontinuation are shown in Figure 2.

Efficacy endpoints

All analyses described here are for OC analysis. Sensitivity analyses using MI‐MAR are shown in Table S3.

Skin efficacy endpoints

The proportion of patients with IGA 0/1 was 27.1% (PNE) and 17.1% (NNE) at LTE baseline, 55.0% (PNE) and 53.4% (NNE) at Week 56 and 62.6% (PNE) and 58.2% (NNE) at Week 104 (Figure 3). The proportion of patients with EASI‐75 was 38.8% (PNE) and 25.8% (NNE) at LTE baseline, 78.8% (PNE) and 81.1% (NNE) at Week 56 and 88.2% (PNE) and 85.4% (NNE) at Week 104 (Figure 4). At Week 104, the proportion of patients with EASI‐50 response was 96.3% (PNE) and 97.3% (NNE), and the proportion of patients with EASI‐90 response was 67.9% (PNE) and 63.8% (NNE) (Figure 4).

FIGURE 3.

Proportion of patients with IGA score of 0/1 up to 104 weeks (safety population). IGA, Investigator's Global Assessment; LTE, long‐term extension; L BL, lead‐in baseline; LTE BL, long‐term extension baseline; MAR, missing at random; MI, multiple imputation; n, number of patients with available data; NNE, no previous nemolizumab experience; OC, observed cases; PNE, previous nemolizumab experience. This analysis was conducted in the safety population, defined as patients who received at least one dose of the study drug. The lead‐in baseline is defined as the last non‐missing value of the lead‐in studies before the first dose of study drug for patients who rolled over to the LTE study within 6 months of the lead‐in study date of last dose. The LTE baseline was the last available measurement prior to the first treatment in this study. Patients with previous nemolizumab experience were treated with nemolizumab at least once before the LTE study. Patients with no previous nemolizumab experience were never exposed to nemolizumab before the LTE study. In OC, all observed data even after use of rescue therapy were included; no imputations were made for missing data.

FIGURE 4.

Proportion of patients with (a) EASI‐75; (b) EASI‐50; and (c) EASI‐90 up to 104 weeks (safety population). EASI‐50/75/90%, 50%/75%/90% improvement in Eczema Area and Severity Index from lead‐in baseline; LTE, long‐term extension; L BL, lead‐in baseline; LTE BL, long‐term extension baseline; MAR, missing at random; MI, multiple imputation; n, number of patients with available data; NNE, no previous nemolizumab experience; OC, observed cases; PNE, previous nemolizumab experience. This analysis was conducted in the safety population, defined as patients who received at least one dose of the study drug. The lead‐in baseline is defined as the last non‐missing value of the lead‐in studies before the first dose of study drug for patients who rolled over to the LTE study within 6 months of the lead‐in study date of last dose. The LTE baseline was the last available measurement prior to the first treatment in this study. Patients with previous nemolizumab experience were treated with nemolizumab at least once before the LTE study. Patients with no previous nemolizumab experience were never exposed to nemolizumab before the LTE study. In OC, all observed data even after use of rescue therapy were included; no imputations were made for missing data.

Mean SCORAD in PNE patients decreased from 64.95 at lead‐in baseline to 35.26 at LTE baseline and to 16.61 at Week 104, and NNE patients from 65.11 at lead‐in baseline to 44.07 at LTE baseline and to 17.09 at Week 104. The antipruritic activity of nemolizumab, as measured by the VAS Pruritus SCORAD sub‐component mean score, was 7.29 at lead‐in baseline, decreasing to 3.94 at LTE baseline, with continued improvement over time to 1.38 at Week 104.

The proportion of patients with VAS Pruritus ≥4‐point improvement at LTE baseline was 58.7% (PNE) and 31.6% (NNE), and 87.2% and 82.0%, respectively, at Week 104 (Figure 5a). The proportion of patients with VAS Pruritus <2 is shown in Figure 5b. Consistent improvements were observed with sleep, as measured by VAS sleep loss SCORAD sub‐component, with mean scores of 6.16 at lead‐in baseline, 3.08 at LTE baseline and 1.32 at Week 104. Figure S1 shows the proportion of patients with ≥4‐point improvement in VAS sleep loss. Health‐related QoL improved from lead‐in baseline to Week 20 with maintenance of response through Week 56 and 104 as assessed by the proportion of patients with DLQI 0 or 1 and the proportion of patients with 4‐point reduction in DLQI (Figure S2). The proportion of patients reporting low disease activity (clear, almost clear or mild based on PGAD) improved from LTE baseline through Week 56 and Week 104, as shown in Figure S3. The proportion of patients reporting satisfaction with study treatment (good, very good or excellent based on PGAT) also improved from the first measurement at Week 4 through Week 56 and Week 104 (Figure S4).

FIGURE 5.

Proportion of patients up to 104 weeks with (a) ≥4‐point improvement from lead‐in baseline in SCORAD VAS Pruritus; (b) SCORAD VAS Pruritus <2. LTE, long‐term extension; L BL, lead‐in baseline; LTE BL, long‐term extension baseline; MAR, missing at random; MI, multiple imputation; N, total number of patients; n, number of patients with available data; NNE, no previous nemolizumab experience; OC, observed cases; PNE, previous nemolizumab experience; SCORAD, SCORing Atopic Dermatitis; VAS, Visual Analogue Scale. Patients were asked to evaluate their symptoms of Pruritus (average for the last 3 days/nights) on a VAS ranging from 0 to 10. This analysis was conducted in the safety population, defined as patients who received at least one dose of the study drug. The lead‐in baseline is defined as the last non‐missing value of the lead‐in studies before the first dose of study drug for patients who rolled over to the LTE study within 6 months of the lead‐in study date of last dose. The LTE baseline was the last available measurement prior to the first treatment in this study. Only patients previously included in the Phase 2b dose‐ranging study, Adolescent pharmacokinetic/safety study, ARCADIA 1 and 2 studies, and Phase 3b study, who rolled over to the LTE study within 6 months of the date of last dose in the lead‐in study contributed to the improvement from lead‐in baseline analyses. Patients with previous nemolizumab experience were treated with nemolizumab at least once before the LTE study. Patients with no previous nemolizumab experience were never exposed to nemolizumab before the LTE study. Percentage (%) was calculated using n as the denominator. In OC, all observed data even after use of rescue therapy were included; no imputations were made for missing data.

Pharmacokinetics

The pharmacokinetic population comprised 1775 patients, including 1099 PNE and 676 NNE patients. Nemolizumab serum concentrations remained stable over the 104‐week treatment period with median concentrations (Q1–Q3 quartiles) of 2.50 μg/mL (1.66–3.57 μg/mL) at Week 20 and 2.50 μg/mL (1.67–3.47 μg/mL) at Week 104. Similar nemolizumab exposure was observed between PNE and NNE patients. Overall, steady‐state conditions were maintained over long‐term treatment with nemolizumab.

Immunogenicity

In the Phase 3 trials (ARCADIA 1, ARCADIA 2) up to 16 weeks, the incidence of treatment‐emergent ADA was 7.6% (84/1100). A similar immunogenicity profile was observed in the ARCADIA LTE, with ADA incidence ranging from 7.4% at Week 20 (120/1617) to 5% at Week 104 (36/718). Median ADA titre over time was low (10‐1280). Two patients tested positive for neutralizing antibodies, one at Week 20 and one at Week 104.

DISCUSSION

In this long‐term study, the safety profile of nemolizumab up to 104 weeks was consistent with that reported in the Phase 3 clinical programme. Nemolizumab was well‐tolerated with no new safety findings identified. There was no increase in AE incidence in nemolizumab‐treated patients (regardless of previous treatment experience), and the majority of AEs were mild‐to‐moderate in severity. The most common study drug‐related TEAEs were AD, asthma, nasopharyngitis and upper respiratory tract infection. The incidence of SAEs was low and no particular clustering pattern of SAEs suggestive of any new safety finding was observed.

Treatment‐emergent AESIs were mild‐to‐moderate, and experienced by 29.2% of patients during the treatment period, most of which were infections (24.9%). Overall, the proportion of patients experiencing an AESI was comparable with that observed in the pivotal studies. There was no evidence of increased risk of serious or severe infections or infections requiring prolonged treatment (with antibiotics, antifungals or antivirals) in association with nemolizumab. The incidence of injection‐site reactions was low. The immunogenicity profile was similar to that reported in Phase 3 pivotal studies, and steady‐state conditions were maintained over long‐term treatment with nemolizumab.

In the ARCADIA LTE, nemolizumab 30 mg Q4W plus background topical therapy was associated with sustained improvements in AD disease activity during prolonged treatment over 104 weeks in PNE and NNE patients, as assessed by the skin efficacy endpoints IGA 0/1 response and EASI‐75 at Week 104. Nemolizumab plus topical therapy improved several measures of AD symptoms including itch and sleep, and patient‐reported outcomes including QoL over 104 weeks. The LTE study also demonstrated 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. The MI‐MAR sensitivity analysis at Week 56 in the safety population supports the observation at 1 year.

This study included a heterogeneous population of patients with different durations of previous exposure to nemolizumab in lead‐in studies; patients who were continuously treated with nemolizumab versus patients who had a gap in treatment of several months, a mix of responders and non‐responders at Week 16 and patients who received placebo with background therapy before enrolling into the LTE. The response to treatment in the NNE patients rapidly converged with the treatment effect experienced by PNE patients.

Although existing non‐biologic and biologic treatment options for patients with moderate‐to‐severe AD provide fast itch relief paired with safety for long‐term use, these treatments are not universally effective and new treatment options are needed. ²⁵ , ²⁶ Nemolizumab showed rapid relief of itch onset as early as Week 1, ³⁴ and therefore addresses the need for a treatment that provides itch relief, known to be a top priority in patients with AD. ²⁶

Long‐term studies were performed in the other currently available biologics used to treat AD, including dupilumab ¹⁷ and tralokinumab. ³⁵ In these studies, efficacy in reducing skin inflammation was similar to that shown in the nemolizumab long‐term study reported here. In a long‐term open‐label study of dupilumab 300 mg weekly in adults with moderate‐to‐severe AD who were previously treated in dupilumab trials, safety data were consistent with those from previous studies for up to 148 weeks, and AD signs and symptoms showed sustained improvements during treatment. ¹⁷ Similarly, a long‐term open‐label extension trial of tralokinumab plus optional topical corticosteroids in patients with moderate‐to‐severe AD from previous tralokinumab trials showed that tralokinumab was well‐tolerated over 2 years and maintained long‐term control of AD. ³⁵ Safety findings were similar to those from placebo‐controlled tralokinumab parent trials, with AEs occurring at lower rates. ³⁵ However, dupilumab, tralokinumab and lebrikizumab ¹⁹ have been associated with ocular surface disease (OSD), whereas no safety concerns related to OSD have been reported with nemolizumab, likely due to its distinct mode of action. Thus, nemolizumab might represent a therapeutic alternative, especially in patients with OSD, other AEs under previous systemic therapies and/or risk factors for JAKIs in addition to patients without previous systemic therapies.

Limitations of the ARCADIA LTE included the open‐label, observed analysis, non‐controlled nature of the study, concomitant use of topical background therapy and that the study was conducted during the COVID pandemic. Not all patients reached Week 104, hence results at Week 104 may vary. The skin endpoint appeared not to reach a plateau, therefore analysis of longer treatment duration is needed to understand the full effect of nemolizumab in the skin.

CONCLUSIONS

The safety data from this interim analysis support the long‐term use of nemolizumab for adolescent and adult patients with moderate‐to‐severe AD. In this LTE study, nemolizumab 30 mg Q4W was associated with sustained improvements in AD disease activity during prolonged treatment, including control of signs and symptoms of AD and QoL over the long term up to 104 weeks.

AUTHOR CONTRIBUTIONS

All authors contributed to the study conception, design, data acquisition, analysis or interpretation, drafted or critically reviewed the manuscript, provided final approval of the version to be published and assume accountability for all aspects of the work to ensure that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

FUNDING INFORMATION

This study was sponsored by Galderma.

CONFLICT OF INTEREST STATEMENT

Matthias Augustin has served as a consultant, lecturer and/or researcher and has received institutional research grants from companies manufacturing drugs for atopic dermatitis, including AbbVie, Almirall, Beiersdorf, Eli Lilly, Galderma, Incyte, LEO Pharma, L'Oréal, Novartis, Pfizer, Regeneron, Roche‐Posay and Sanofi‐Genzyme. Marie Tauber has served as an advisor and/or paid speaker for and/or participated in clinical trials sponsored by AbbVie, Almirall, Boehringer Ingelheim, Galderma, Janssen‐Cilag, LEO Pharma, Eli Lilly, MEDAC, Novartis, Pfizer and Sanofi; and has received consulting fees from Almirall, Janssen‐Cilag, LEO Pharma and Sanofi. Robert Sidbury has served as an investigator and/or participated in advisory boards for Arcutis, Avene, Castle, Dermavent, Galderma, LEO Pharma, Eli Lilly, Pfizer, Regeneron and UCB; been a speaker at Beiersdorf; had institutional contracts with Regeneron and Incyte (as an investigator on studies); received consulting fees from Leo, Lilly, and Alphyn; served as an (unpaid) board member of the Society for Pediatric Dermatology and the Washington State Dermatology Association. Jonathan Silverberg has received honoraria as a consultant and/or advisory board member from AbbVie, Afyx, Aobiome, Arena, Asana, Aslan, BioMX, Bluefin, Bodewell, Boehringer‐Ingelheim, Celgene, Connect Biopharma, Dermavant, Dermira, Eli Lilly, Galderma, GlaxoSmithKline, Incyte, Kiniksa, LEO Pharma, Luna, Menlo, Novartis, Pfizer, RAPT, Regeneron and Sanofi‐Genzyme and as a speaker from AbbVie, Eli Lilly, LEO Pharma, Pfizer, Regeneron and Sanofi‐Genzyme; his institution has received grants from Galderma and Pfizer. Kim A Papp has received clinical research grants, honoraria and/or consultant fees and/or served as a scientific advisor, investigator, speaker and/or medical officer: AbbVie, Acelyrin, Akros, Alumis, Amgen, Arcutis, Bausch Health/Valeant, Boehringer Ingelheim, Bristol Myers Squibb, Can‐Fite, Celltrion, Concert, Dermavant, Dermira, Dice Pharmaceuticals, Dice Therapeutics, Eli Lilly, Evelo, Forbion, Galderma, Horizon, Incyte, Johnson and Johnson, Kymab, Kyowa Hakko Kirin, LEO, Meiji Seika, Mitsubishi, Nimbus, Novartis, Pfizer, Reistone, Sanofi‐Aventis/Genzyme, Sandoz, Sun, Takeda, Tarsus, UCB and Zai Lab Co. Diamant Thaçi is a lecturer and/or consultant for AbbVie, Almirall, Amgen, Boehringer‐Ingelheim, Bristol Myers Squibb, Celltrion, Galderma, Genzyme, Incyte, Johnson & Johnson, Kyowa Kirin, LEO Pharma, L'Oréal, Eli Lilly, New Bridge, Novartis, Pfizer, Regeneron, Sanofi, Stada, Sun‐Pharma, Target RWE, UCB and Vichy and received grants from AbbVie, LEO and Novartis (paid to institution). Marjolein S. De Bruin‐Weller has served as an investigator for AbbVie, Almirall, Amgen, Eli Lilly, Galderma, Leo Pharma, Pfizer, Regeneron Pharmaceuticals, Inc. and Sanofi‐Genzyme, and has received honoraria from AbbVie, Almirall, Amgen, Arena, Aslan, Eli Lilly, Galderma, Janssen, Leo Pharma, Pfizer, Regeneron and Sanofi‐Genzyme. Adam Reich has served as an investigator and/or participated in advisory boards for AbbVie, Alvotech, Amgen, AnaptysBio, Arcutis, Biogen, Biotherapy, Bristol Myers Squibb, Celgene, Celltrion, Dermira, Galderma, Inflarx, Janssen, Kiniksa, Kymab, LEO Pharma, Novartis, Pfizer, Pierre Fabre, Trevi Therapeutics and UCB, and has received honoraria from Chema Rzeszów, Eli Lilly, LEO Pharma, Novartis, Sandoz and Takeda. Ketty Peris reports grants and personal fees from Almirall and AbbVie during the conduct of the study, and personal fees from Biogen, Eli Lilly, Galderma, Leo Pharma, Novartis, Pierre Fabre, Philogen, Sanofi, Sun Pharma and Janssen outside the submitted work. Kirk Barber has served as a consultant, investigator and/or speaker for AbbVie, Allergan, Amgen, Anacor, Aristea, Arcutis, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, BioPharma, Celgene, Celltrion, Centacor, Concert Pharmaceuticals, Dermavant, Dermira, Dice, Dow Pharma, Eli Lilly, Galderma, GlaxoSmithKline, Incyte, Janssen, LEO Pharma, Merck, Nimbus Lakshmi Inc., National Institute of Health, Novartis, Pfizer, Regeneron, Roche, Sandoz, Sanofi, Sun Pharma, Takeda, UCB, Valeant, Wyeth, Xenon. Ryszard Galus has served as an investigator for Galderma, Amgen, Chugai, Dermira, Glenmark, Incyte, Kymab, Pfizer, Regeneron Pharmaceuticals Inc., Sanofi and reported personal fees from Synexus; lecturer at the Medical University of Warsaw. Andrzej Kaszuba is an investigator for Galderma. Matthew Zirwas is a consultant and investigator or a speaker for AbbVie, Acrotech, Advanced Derm Solutions, Aldeyra, All Free Clear / Sun, Amgen, Anaptys Bio, Apogee, Arcutis, Bausch and Lomb, Beiersdorf, Biocon, Bristol Myers Squibb, Celldex, Cara, Sun, Dermavant, Evommune, Evelo, Galderma, Google, Incyte, Janssen, L'Oréal, Leo, Lilly, LUUM, Meta, Nimbus, Novan, Novartis, Pfizer, Q32 Bio, Regeneron, Sanofi, Supernus, Takeda, Trevi, Trifecta, UCB and Verrica. Walter K Nahm is an investigator for Galderma. Gretel Trullenque is an investigator for Galderma. Laura Maintz has served as an investigator for AbbVie, Anaptys Bio, Almirall, Amgen, Bioprojet, Bristol‐Myers Squibb, Eli Lilly, Galderma, LEO Pharma, Numab, OM Pharma, Pfizer, Sanofi/Regeneron, UCB; an advisor for AbbVie, Almirall, LEO Pharma, Sanofi/Regeneron; received speaker honoraria from AbbVie, Almirall, Eli Lilly, LEO Pharma, Sanofi/Regeneron; received research funding from CK‐CARE, Eli Lilly, LEO Pharma and Sanofi/Regeneron; and received reimbursement for travel costs from Pfizer. Sady Alpizar is an investigator for Galderma. Sang Wook Son is an investigator for Galderma. Vivian T. Laquer has served as investigator for AbbVie, Acelyrin, Acrotech, Amgen, Argenx, Arcutis, Aslan, Biofrontera, Bristol Myers Squibb, Cara, Dermavant, Eli Lilly, Galderma, Horizon Therapeutics, Incyte, Janssen, Leo, Novartis, Padagis, Pfizer, Q32, Rapt, Sun, UCB and Ventyx. Linda Stein Gold has received grants, contracts, consulting fees, payments or honoraria from Galderma, AbbVie, Amgen, BMS, J&J, Lilly, Leo, Sanofi, Regeneron, Incyte and Arcutis, and is an investigator for Allergan plc and Galderma. Soo Yeon Cheong, Anna Ryzhkova, Agnes Drahos and Christophe Piketty are employees of Galderma. Liliana Ulianov is an employee of Galderma and holds stock or stock options.

ETHICAL APPROVAL

Ethical approval was obtained from each relevant institutional review board (IRB) or independent ethics committee (IEC). The study was conducted in accordance with the ethical principles of the Declaration of Helsinki (1964), the International Council for Harmonization (ICH) Good Clinical Practice (GCP) guidelines and the applicable national and local laws and regulatory requirements.

ETHICS STATEMENT

All patients were required to provide written informed consent.

Supporting information

Table S1. Additional methodology. (A) Eligibility criteria; (B) background topical therapy.

Table S2. Efficacy endpoints at all visits.

Table S3. Sensitivity analyses.

Figure S1. Proportion of patients up to 104 weeks with ≥4‐point improvement from lead‐in baseline in SCORAD VAS Sleep Loss. LTE, long‐term extension; L BL, lead‐in baseline; LTE BL, long‐term extension baseline; MAR, missing at random; MI, multiple imputation; N, total number of patients; n, number of patients with available data; NNE, no previous nemolizumab experience; OC, observed cases; PNE, previous nemolizumab experience; SCORAD, SCORing Atopic Dermatitis; VAS, visual analogue scale. Patients were asked to evaluate their symptoms of sleep loss (average for the last 3 days/nights) on a VAS ranging from 0 to 10. This analysis was conducted in the safety population, defined as patients who received at least one dose of the study drug. The lead‐in baseline is defined as the last non‐missing value of the lead‐in studies before the first dose of study drug for patients who rolled over to the LTE study within 6 months of the lead‐in study date of last dose. The LTE baseline was the last available measurement prior to the first treatment in this study. Only patients previously included in the Phase 2b dose‐ranging study, Adolescent pharmacokinetic/safety study, ARCADIA 1 and 2 studies and Phase 3b study, who rolled over to LTE study within 6 months of the date of last dose in the lead‐in study contributed to the improvement from lead‐in baseline analyses. Patients with previous nemolizumab experience were treated with nemolizumab at least once before the LTE study. Patients with no previous nemolizumab experience were never exposed to nemolizumab before the LTE study. Percentage (%) was calculated using n as the denominator. In OC, all observed data even after use of rescue therapy were included; no imputations were made for missing data.

Figure S2. Proportion of patients up to 104 weeks with (A) ≥4‐point reduction in DLQI from lead‐in baseline; and (B) DLQI 0/1. DLQI, Dermatology Life Quality Index; LTE, long‐term extension; L BL, lead‐in baseline; LTE BL, long‐term extension baseline; n, number of patients with available data; NNE, no previous nemolizumab experience; OC, observed cases; PNE, previous nemolizumab experience. This analysis was conducted in the safety population, defined as patients who received at least one dose of the study drug. The lead‐in baseline is defined as the last non‐missing value of the lead‐in studies before the first dose of study drug for patients who rolled over to the LTE study within 6 months of the lead‐in study date of last dose. The LTE baseline was the last available measurement prior to the first treatment in this study. Only patients previously included in the Phase 2b dose‐ranging study, adolescent pharmacokinetic/safety study, ARCADIA 1 and 2 studies and Phase 3b study, who rolled over to the LTE study within 6 months of the date of last dose in the lead‐in study contributed to the improvement from lead‐in baseline analyses. Patients with previous nemolizumab experience were treated with nemolizumab at least once before the LTE study. Patients with no previous nemolizumab experience were never exposed to nemolizumab before the LTE study. DLQI score ranges from 0 to 30. The higher the score, the more quality of life is impaired. Percentage (%) was calculated using n as the denominator. In OC, all observed data even after use of rescue therapy were included; no imputations were made for missing data.

Figure S3. Proportion of patients reporting low disease activity (clear, almost clear, or mild based on PGAD). LTE, long‐term extension; L BL, lead‐in baseline; LTE BL, long‐term extension baseline; N, total number of patients; n, number of patients with available data; NNE, no previous nemolizumab experience; OC, observed cases, PGAD, Patient Global Assessment of Disease; PNE, previous nemolizumab experience. This analysis was conducted in the safety population, defined as patients who received at least one dose of the study drug. The LTE baseline was the last available measurement prior to the first treatment in this study. Patients with previous nemolizumab experience were treated with nemolizumab at least once before the LTE study. Patients with no previous nemolizumab experience were never exposed to nemolizumab before the LTE study. PGAD scores range from ‘clear’ to ‘severe’ on a 5‐point Likert scale. Percentage (%) was calculated using n as the denominator. In OC, all observed data even after use of rescue therapy were included; no imputations were made for missing data.

Figure S4. Proportion of patients reporting satisfaction with study treatment (good, very good or excellent based on PGAT). LTE, long‐term extension; LTE BL, long‐term extension baseline; N, total number of patients; n, number of patients with available data; NNE, no previous nemolizumab experience; OC, observed cases, PGAT, Patient Global Assessment of Treatment; PNE, previous nemolizumab experience. This analysis was conducted in the safety population, defined as patients who received at least one dose of the study drug. Patients with previous nemolizumab experience were treated with nemolizumab at least once before the LTE study. Patients with no previous nemolizumab experience were never exposed to nemolizumab before the LTE study. PGAT scores range from ‘poor’ to ‘excellent’ on a 5‐point Likert scale.

Augustin M, Tauber M, Sidbury R, Silverberg JI, Papp KA, Thaçi D, et al. Safety and efficacy of nemolizumab for atopic dermatitis up to 2 years in open‐label extension study. J Eur Acad Dermatol Venereol. 2026;40:841–855. 10.1111/jdv.70080

DATA AVAILABILITY STATEMENT

The data that support the findings of this study are available from the corresponding author upon request to clinical.studies@galderma.com.