Dupilumab Treatment in Pediatric Patients Aged 6-11 Years with Severe Atopic Dermatitis Whose Disease Is Not Adequately Controlled: A Review.

Atopic dermatitis (AD) is the most common inflammatory skin disease in children. Children with severe AD have a multidimensional disease burden characterized by skin lesions, itching, frequent infections, sleep deprivation, and a high rate of comorbidities. These impact the mental health and overall quality of life of not only the children but also of their parents and caregivers. There are few effective available treatment options for young children with severe AD that are suitable for long-term use. Due to their adverse effects, practice guidelines consider systemic agents inappropriate for this age group, although they are still used off-label in extreme cases. The biologic dupilumab has recently been approved for children aged 6-11 years with severe (EU) and moderate-to-severe (USA) AD, offering hope to this population of patients with a high unmet clinical need. The purpose of this review is to describe the unmet needs of AD patients aged 6-11 years prior to dupilumab approval and to summarize existing clinical data supporting dupilumab's safety and efficacy in these children.

Burden of Atopic Dermatitis in Pediatric Patients: An International Cross-sectional Study.

BACKGROUND: Few large-scale international studies broadly characterized the burden of atopic dermatitis (AD) across age groups among children and adolescents. OBJECTIVE: To better characterize the AD burden in pediatric subjects by disease severity. METHODS: This cross-sectional, web-based survey of pediatric subjects (6 months to <18 years old) was conducted in 18 countries representing North America, Latin America, Europe, Middle East/Eurasia, and East Asia. Subjects with diagnosed AD were identified based on the International Study of Asthma and Allergies in Childhood criteria and self-/parent-report of ever being told by a physician that they/their child had eczema. AD severity was assessed using Patient Oriented Eczema Measure and Patient Global Assessment. Outcomes included measures of itch, skin pain, sleep, health-related quality-of-life (HRQoL), missed school days, and atopic comorbidities. RESULTS: The survey included 1489 children 6 months to < 6 years; 2898 children 6 to < 12 years; and 3078 adolescents 12 to < 18 years diagnosed with AD. Although the burden of mild AD was substantial, pediatric subjects with moderate or severe AD had more itch, skin pain, sleep problems, and impaired HRQoL, and missed more school days relative to those with mild AD; greater burden was observed among severe relative to moderate AD. At least one atopic comorbidity was present in 92·5% of all respondents. CONCLUSIONS: These results highlight the burden of AD in pediatric subjects especially those with moderate-to-severe disease, and suggest the need for assessments that include the impact of AD on function and daily life.

The disease burden of pediatric patients with atopic dermatitis in Japan.

BACKGROUND: Atopic dermatitis (AD) is a chronic skin condition that is associated with significant patient burden and decreased health-related quality of life (HRQoL). We report results of the real-world Epidemiology of Children with Atopic Dermatitis Reporting on their Experience study in Japanese pediatric patients, focusing on the impact of AD severity on disease burden. METHODS: Children and adolescents aged 6 months to 17 years (or their caregivers/parents) completed an online survey between September 26, 2018, and March 5, 2019. Patients with diagnosed AD (i.e., met International Study of Asthma and Allergies in Childhood criteria and had a self-reported AD diagnosis) were evaluated for disease severity using the Patient-Oriented Eczema Measure (POEM). Impact of AD severity on AD symptoms (itching, pain, and sleep disturbance), disease flares, atopic comorbidities, healthcare resource utilization, school days missed, and HRQoL were assessed. RESULTS: Of 5702 Japanese pediatric patients, 547 had diagnosed AD and were included in this analysis. Based on POEM scores, AD severity was clear/mild in 346 patients (63.3%), moderate in 177 (32.5%), and severe in 24 (4.4%). Across all age groups (i.e., less than 6, 6-11, and 12-17 years), increased AD severity was associated with increased AD symptom severity, number of flares, atopic comorbidities, healthcare resource utilization, and school absences, as well as worsened HRQoL. CONCLUSIONS: This population-based study of Japanese children and adolescents showed that greater AD severity had a high impact on disease burden.

Dupilumab Provides Clinically Meaningful Responses in Children Aged 6-11 Years with Severe Atopic Dermatitis: Post Hoc Analysis Results from a Phase III Trial.

BACKGROUND: Children with severe atopic dermatitis (AD) have a multidimensional disease burden. OBJECTIVE: Here we assess the clinically meaningful improvements in AD signs, symptoms, and quality of life (QoL) in children aged 6-11 years with severe AD treated with dupilumab compared with placebo. METHODS: R668-AD-1652 LIBERTY AD PEDS was a randomized, double-blinded, placebo-controlled, parallel-group, phase III clinical trial of dupilumab with concomitant topical corticosteroids (TCS) in children aged 6-11 years with severe AD. This post hoc analysis focuses on 304 patients receiving either dupilumab or placebo with TCS and assessed the percentage of patients considered responsive to dupilumab treatment at week 16. RESULTS: At week 16, almost all patients receiving dupilumab + TCS (95%) demonstrated clinically meaningful improvements in AD signs, symptoms, or QoL compared with placebo + TCS (61%, p < 0.0001). Significant improvements were seen as early as week 2 and sustained through the end of the study in the full analysis set (FAS) and the subgroup of patients with an Investigator's Global Assessment score greater than 1 at week 16. LIMITATIONS: Limitations include the post hoc nature of the analysis and that some outcomes were not prespecified; the small number of patients in some subgroups potentially limits generalizability of findings. CONCLUSION: Treatment with dupilumab provides significant and sustained improvements within 2 weeks in AD signs, symptoms, and QoL in almost all children with severe AD, including those who did not achieve clear or almost clear skin by week 16. TRIAL REGISTRATION: NCT03345914. Video Abstract: Does dupilumab provide clinically meaningful responses in children 6 to 11 years old with severe atopic dermatitis? (MP4 99484 kb).

Impact of the Family and Household Environment on Pediatric Atopic Dermatitis in Japan.

Pediatric atopic dermatitis (AD) can negatively impact the family quality of life (QoL). We report data from the real-world Epidemiology of Children with Atopic Dermatitis Reporting on their Experience (EPI-CARE) study in Japanese pediatric patients, focusing on disease impact on family QoL. Children and adolescents aged 6 months to <18 years completed an online survey between September 2018-December 2019. The impact of disease severity on family QoL and its effect on parents' time were assessed using the dermatitis family impact (DFI) questionnaire. The impact of a family history of allergic conditions, current residency, second-hand smoke exposure, and household pets on AD prevalence and severity was also assessed. Family QoL decreased as AD severity increased, particularly in families with children aged <6 years; but had the greatest impact on sleep and tiredness in families with children aged <12 years. Parents spent at least 4.6 h/week caring for children <6 years, including those with mild symptoms. Most children (>80%) had a family history of allergic conditions; AD prevalence was increased in those exposed to second-hand smoke or household pets. This study demonstrated that pediatric AD in Japanese individuals has negative impacts on family QoL and that family and household environments can influence pediatric AD prevalence.

Implications of Atopic Dermatitis on the Quality of Life of 6-11 Years Old Children and Caregivers (PEDI-BURDEN).

Purpose: Atopic dermatitis (AD) is a chronic, relapsing and remitting inflammatory skin disease characterized by intense itch. The disease burden includes physical limitations, psychosocial discomfort, and a reduced quality of life (HRQoL). This study presents the results of a parent-reported survey on the psychosocial impact of AD on Italian pre-adolescent children (6-11 years old), with a specific focus on bullying, self-isolation, absenteeism, and presenteeism. Methods: An online questionnaire was sent to 3067 random recipients and 160 matched the inclusion criteria for age, self-reported AD diagnosis, localizations (according to ISAAC), and disease severity (POEM ≥8). 100 children, with comparable ages, not matching the inclusion criteria for AD, were recruited as a control group. Results: Children with AD and their caregivers had a significantly lower quality of sleep (QoS) compared to the control group. The presence of AD was directly responsible for many restless nights, both in children and caregivers (58.9 and 55.4 respectively). Children with AD and their parents also experienced significantly more daytime drowsiness (43.6 and 54.6 days, respectively). Children with AD were more frequently victims of bullying at school (20.0% vs 9.0%; p≤0.05) or in other social environments (16.9% vs 3.0%; p≤0.05). AD caused 17.7 days of absenteeism and 20.1 days of presenteeism per student over the previous 12 months, accounting for 37.8 days of study impairment overall. Severe/very severe AD had a significantly greater impact on presenteeism than moderate AD (25.1 vs 17.5 days; p≤0.05). Presenteeism, which was more pronounced among bullied students, was positively correlated with absenteeism only in the AD cohort. Conclusion: AD has a detrimental impact on the HRQoL of pediatric patients, causing stigmatization and social isolation. Functional distress was also reported by caregivers. Our study might inform the public and policymakers about the disease burden of AD at a young age.

Efficacy and Safety of Dupilumab in Patients With Erythrodermic Atopic Dermatitis: A Post Hoc Analysis of 6 Randomized Clinical Trials.

Importance: Erythrodermic atopic dermatitis (AD) is a severe AD subtype defined by extensive skin involvement, leading to complications and sometimes hospitalization. Objective: To assess dupilumab's efficacy and safety in patients with erythrodermic AD in clinical trials. Design, Setting, and Participants: This post hoc analysis included patients enrolled in 6 multicenter, multinational, randomized, double-blind, placebo-controlled trials. Patients included in this analysis met erythrodermic AD criteria of 90% or greater body surface area (BSA) affected by AD and Global Individual Sign Score for erythema of 1 or higher. Data analyses for this post hoc analysis were conducted between March 5, 2019, and October 24, 2020. Interventions: Dupilumab once weekly or every 2 weeks, or placebo, either as monotherapy or with concomitant topical corticosteroids (TCS). Main Outcomes and Measures: Efficacy (BSA, Eczema Area and Severity Index [EASI] score, Peak Pruritus Numerical Rating Scale [PP-NRS] score), changes in serum biomarkers (thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase), and safety (incidence of adverse events) at week 16. Data were pooled within each regimen; monotherapy and concomitant TCS results are shown separately. Results: Of 3075 randomized patients, 209 met criteria for erythrodermic AD at baseline, with the median age being 31 and 39 years in the monotherapy and concomitant TCS trials, respectively, similar to the overall populations (34 and 36 years, respectively); 71.3% (n = 97) and 74.0% (n = 54) of patients, respectively, were male (compared with 58.7% and 60.6% in the overall populations). In patients with erythrodermic AD, dupilumab once weekly and every 2 weeks vs placebo significantly improved percentage of BSA affected by AD (least squares mean percent change [SE]) with monotherapy (-42.0% [7.7%] and -39.9% [6.5%] vs -17.2% [11.0%]; P = .03) and concomitant TCS (-63.2% [6.7%] and -56.1% [9.1%] vs -14.5% [7.3%]; P < .001); EASI score with monotherapy (-58.5% [9.0%] and -58.3% [7.9%] vs -22.3% [12.4%]; P = .004 and P = .003, respectively) and concomitant TCS (-78.9% [7.8%] and -70.6% [10.1%] vs 19.3% [8.2%]; P < .001); and PP-NRS score in monotherapy (-45.9% [7.8%] and -33.9% [6.6%] vs -0.6% [9.4%]; P < .001) and concomitant therapy (-53.0% [8.1%] and -55.7% [10.8%] vs -26.0% [8.8%]; P = .006 and P = .01, respectively). Nominally statistically significant improvement was seen as early as week 1 (EASI and PP-NRS scores with monotherapy). Biomarker levels were significantly reduced vs placebo. The most frequent adverse events in dupilumab-treated patients were injection-site reaction, conjunctivitis, and nasopharyngitis. Conclusions and Relevance: In this post hoc analysis of 6 randomized clinical trials, treatment with dupilumab resulted in rapid, sustained improvements in AD signs and symptoms with acceptable safety in patients with erythrodermic AD, similar to those in the trials' overall patient population. Trial Registration: ClinicalTrials.gov Identifiers: NCT01859988, NCT02277743, NCT02277769, NCT03054428, NCT02260986, NCT02755649.

Dupilumab Treatment in Adults with Moderate-to-Severe Atopic Dermatitis is Efficacious Regardless of Age of Disease Onset: a Post Hoc Analysis of Two Phase 3 Clinical Trials.

INTRODUCTION: Adults with atopic dermatitis (AD) commonly report adult-onset disease. AD is associated with different genetics, lesion morphology and distribution, and symptoms by age of onset. Yet little is known about possible differences in treatment efficacy between adults with adult-onset or childhood-onset AD. METHODS: We evaluated the efficacy of dupilumab by age of AD onset in adults with moderate-to-severe AD, using pooled data from the LIBERTY AD SOLO 1 and 2 studies (NCT02277743, NCT02277769). Results were stratified based on self-reported age of AD onset, divided into four age subgroups: 0-4, 5-9, 10-19, and over 20 years. RESULTS: This analysis included 460 patients treated with placebo and 457 treated with dupilumab 300 mg every 2 weeks (q2w), with a mean patient age of 38 years. Most patients (53.2%) reported AD onset at 0-4 years, with 14% at 5-9 years, 13.4% at 10-19 years, and 18.5% at 20 years or older. Dupilumab significantly improved AD signs and symptoms over 16 weeks compared with placebo, regardless of age of onset. Dupilumab treatment resulted in a significantly greater proportion of patients achieving Eczema Area and Severity Index (EASI)-50, EASI-75, and EASI-90 (50%, 75%, and 90% improvement from baseline EASI, respectively), and clear or almost clear skin (Investigator's Global Assessment score 0 or 1) across all age-of-onset subgroups compared with placebo. In addition, EASI improvements were significant across all anatomical regions in all subgroups. Weekly average peak pruritus Numerical Rating Scale and Dermatology Life Quality Index also improved consistently and significantly with dupilumab versus placebo, regardless of age of onset. CONCLUSION: Despite possible differences in presentation and progression of AD linked to age of onset, dupilumab showed similar significant and sustained improvements in AD signs, symptoms, and quality of life in adults compared with placebo, over 16 weeks of treatment. TRIAL REGISTRATION: LIBERTY AD SOLO 1: NCT02277743; LIBERTY AD SOLO 2: NCT02277769. Infographic available for this article.

Atopic dermatitis (AD, also known as eczema) is a skin disease with itchy, red rashes. AD often develops during childhood, but can also start in adulthood. Depending on the age it starts, AD may have different triggers and appearance, and might require different treatment. A medicine called dupilumab, which targets two proteins that cause inflammation, has provided benefit in children and adults with AD. We wanted to know if the age at which AD starts (during infancy, childhood, adolescence, or adulthood) impacts the improvement of dupilumab in adult patients. We looked at 917 adults, who participated in two studies taking dupilumab or a dummy treatment (placebo) every 2 weeks for 4 months. We compared four groups of patients with different ages of AD onset. The results showed that dupilumab compared with the placebo reduced skin lesions, relieved itch, and improved quality of life in a similar way in all adults, regardless of whether their disease started earlier or later in life. In the four groups, dupilumab reduced skin lesions across all areas of the body. Together with the previously reported safety data, our results support the use of dupilumab in adults with moderate-to-severe AD, irrespective of age of disease onset. INFOGRAPHIC.

Type 2 Inflammation Contributes to Skin Barrier Dysfunction in Atopic Dermatitis.

Skin barrier dysfunction, a defining feature of atopic dermatitis (AD), arises from multiple interacting systems. In AD, skin inflammation is caused by host-environment interactions involving keratinocytes as well as tissue-resident immune cells such as type 2 innate lymphoid cells, basophils, mast cells, and T helper type 2 cells, which produce type 2 cytokines, including IL-4, IL-5, IL-13, and IL-31. Type 2 inflammation broadly impacts the expression of genes relevant for barrier function, such as intracellular structural proteins, extracellular lipids, and junctional proteins, and enhances Staphylococcus aureus skin colonization. Systemic anti‒type 2 inflammation therapies may improve dysfunctional skin barrier in AD.

Dupilumab significantly improves skin barrier function in patients with moderate-to-severe atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is characterized by abnormal skin lipids that are largely driven by hyperactivated type 2 immune responses. The antibody to the α-subunit of interleukin (IL)-4 receptor, dupilumab, was recently approved to treat AD and demonstrated strong efficacy. However, the role of dupilumab therapy in the regulation of skin barrier structure and function has not been fully explored. METHODS: We have evaluated the content of lipids and transepidermal water loss (TEWL) in lesional and non-lesional skin of adults and adolescents with moderate-to-severe AD over the course of 16-week treatment with dupilumab and compared those values with that of matched healthy volunteers. RESULTS: Dupilumab treatment provided a significant decrease in TEWL in AD lesions, lowering it almost to the levels seen in the skin of healthy subjects. Blocking IL-4/IL-13 signaling with dupilumab normalized lipid composition (decreased levels of ceramides with non-hydroxy fatty acids and C18-sphingosine and increased the level of esterified omega-hydroxy fatty acid-containing ceramides) and increased ceramide chain length in lesional as well as non-lesional stratum corneum of AD patients. Partial changes for these parameters were already observed after 2 weeks, with a full response achieved after 8 weeks of dupilumab treatment. CONCLUSIONS: Inhibition of IL-4/IL-13 signaling by dupilumab allows restoration of skin lipid composition and barrier function in patients with moderate-to-severe AD.

The Family Impact of Atopic Dermatitis in the Pediatric Population: Results from an International Cross-sectional Study.

OBJECTIVE: To evaluate the impact of atopic dermatitis on families of pediatric patients. STUDY DESIGN: This cross-sectional, web-based survey of children/adolescents (6 months to <18 years old) with atopic dermatitis and their parents and caregivers was conducted in 18 countries encompassing North America, Latin America, Europe, Middle East/Eurasia, and East Asia. Children and adolescents with atopic dermatitis and their parents and caregivers were identified by the International Study of Asthma and Allergies in Childhood criteria and ever being told by a physician that they had "eczema". Atopic dermatitis severity was assessed using the Patient-Oriented Eczema Measure and the Patient Global Assessment. Atopic dermatitis impact on families' lives was evaluated using the Dermatitis Family Impact questionnaire and stand-alone questions on hours of atopic dermatitis-related care (past week) and missed work days (past 4 weeks) owing to their child's atopic dermatitis. RESULTS: A total of 7465 pairs of pediatric participants with atopic dermatitis and their parents or caregivers were surveyed. Across age groups, the Dermatitis Family Impact questionnaire total score for all regions ranged from 7.1 to 8.6, 13.2 to 14.9, and 17.0 to 17.2 for Patient-Oriented Eczema Measure mild, moderate, and severe atopic dermatitis, respectively. Subscale scores showed that greater atopic dermatitis severity had a greater impact on all family life domains, including sleep and tiredness. No specific patterns or trends were observed across age groups. Time spent on childcare and missed work days increased with atopic dermatitis severity. CONCLUSIONS: Across pediatric age groups and geographic regions, greater atopic dermatitis severity was associated with a greater negative impact on physical, emotional, social, and economic components of family life.

Dupilumab Provides Rapid and Sustained Improvement in SCORing Atopic Dermatitis Outcomes in Paediatric Patients with Atopic Dermatitis.

This post hoc analysis examined SCORing Atopic Dermatitis (SCORAD) outcomes in 471 paediatric patients (children age 6-<12 years, n = 304; adolescents age 12-<18 years, n = 167) with atopic dermatitis treated with dupilumab, ± topical corticosteroids, in two 16-week phase 3 randomized controlled trials and a 1-year interim data cut of a subsequent open-label extension study. Paediatric patients treated with dupilumab (± topical corticosteroids) had significantly lower SCORAD, objective SCORAD (o-SCORAD), and individual SCORAD components from week 3 to 16 compared with placebo (± topical corticosteroids) in the randomized controlled trials. The results were sustained or continuously improved over 1 year of open-label treatment with dupilumab ± topical corticosteroids. SCORAD-50 was achieved in almost all patients (91.3-91.8%) by week 52 with continued dupilumab treatment across age groups. Almost all (> 86%) patients achieved mild or absent pruritus and sleep loss at week 52. In conclusion, dupilumab ± topical corticosteroids resulted in rapid and significant improvements in all aspects of SCORAD analysed, and the results were sustained over 1 year.

Dupilumab Demonstrates Rapid Onset of Response Across Three Type 2 Inflammatory Diseases.

BACKGROUND: Type 2 inflammatory diseases often coexist in patients. Dupilumab targets type 2 inflammation and has demonstrated treatment benefits in patients with atopic dermatitis (AD), asthma, and chronic rhinosinusitis with nasal polyps (CRSwNP) with an acceptable safety profile. OBJECTIVE: This post hoc analysis across five phase 3 studies in patients with moderate to severe AD or asthma, or severe CRSwNP, evaluated time of onset and duration of the treatment response. METHODS: Patients received subcutaneous dupilumab 200/300 mg or placebo. Assessments included the Eczema Area and Severity Index, Peak Pruritus Numerical Rating Scale, and Dermatology Life Quality Index in AD; pre-bronchodilator FEV1, daily morning peak expiratory flow, and symptom scores in asthma; and University of Pennsylvania Smell Identification Test, daily nasal congestion, and loss of smell scores in CRSwNP. RESULTS: At week 2 after the initiation of dupilumab versus placebo, 67.8% versus 36.5% of AD patients achieved a clinically meaningful benefit (Eczema Area and Severity Index: 50% or greater improvement; Peak Pruritus Numerical Rating Scale: 3 point or greater improvement; or Dermatology Life Quality Index: 4 point or greater improvement) (P < .001). Moreover, 61.6% versus 39.9% of asthma patients achieved improvements in pre-bronchodilator FEV1 of 100 mL or greater and 48.8% versus 26.3% achieved 200 mL or greater improvement (both P < .001); 33.2% versus 5.6% of CRSwNP patients regained a sense of smell (P < .001). Treatment effects further improved or were sustained to the end of treatment. CONCLUSIONS: Clinically meaningful responses were achieved rapidly after the first dupilumab dose in AD, asthma, or CRSwNP and were sustained throughout treatment (see Video in this article's Online Repository at www.jaci-inpractice.org).

Dupilumab Treatment Reduces Hospitalizations in Adults With Moderate-to-Severe Atopic Dermatitis.

BACKGROUND: Refractory disease, flares, or infections in atopic dermatitis (AD) can lead to hospitalizations. OBJECTIVE: To compare hospitalization rates among adults with moderate-to-severe AD treated with dupilumab versus control. METHODS: Data from 7 randomized, placebo-controlled trials of dupilumab (300 mg every 2 weeks [q2w] and/or weekly [qw]; with or without topical corticosteroids) were analyzed. RESULTS: Patients in the dupilumab 300 mg q2w, qw, and combined dupilumab (q2w and qw; n = 1,841) groups compared with patients in the control group (n = 1,091) had lower rates of all-cause hospitalizations (5.8, 2.7, and 3.8 events, respectively, vs 9.0 events per 100 patient-years [PY]; all P < .05 [49%, 71%, and 62% risk reduction, respectively]); AD-related hospitalizations (2.0, 0.4, 1.0 events vs 4.1 events per 100 PY; P < .05 for qw and dupilumab combined [91% and 79% risk reduction, respectively]); as well as reduced overall duration of AD-related hospitalization (10.9, 7.3, and 8.6 d vs 38.9 d per 100 PY). CONCLUSIONS: Among adults with moderate-to-severe AD, treatment with dupilumab versus control was associated with significant reductions in all-cause and AD-related hospitalization rates, and shorter duration of AD-related hospitalization.

Consistency of Response to Dupilumab in Adults with Moderate-to-Severe Atopic Dermatitis Over 1 Year.

Video (MP4 113130 kb).

Continued Treatment with Dupilumab is Associated with Improved Efficacy in Adults with Moderate-to-Severe Atopic Dermatitis Not Achieving Optimal Responses with Short-Term Treatment.

INTRODUCTION: Previous drug survival studies of dupilumab in atopic dermatitis (AD) show that many patients continue treatment through 1 year, suggesting that patients experience clinically relevant benefits with long-term treatment. METHODS: This post hoc analysis included data through week 100 from 391 adult patients from the dupilumab open-label extension (OLE) study who had not achieved the endpoints of at least 75% improvement from baseline in the Eczema Area and Severity Index (EASI-75) or an Investigator's Global Assessment (IGA) score of 0 or 1 with short-term (16 weeks, 300 mg qw or q2w) dupilumab treatment in the parent SOLO 1 or 2 studies. All patients received dupilumab 300 mg qw in the OLE study, irrespective of whether they received qw or 2qw dosing in the parent study. RESULTS: Among those who had not achieved EASI-75 or IGA 0/1 during the 16-week parent study, the proportion of patients achieving EASI-75 by week 100 was 91%. The proportion achieving IGA 0 or 1 at week 100 was 45% for patients initially on q2w week dosing and 49% for those on initial qw dosing. CONCLUSION: Long-term dupilumab treatment may be associated with improvement in AD in patients with suboptimal responses during the initial 16 weeks of treatment. CLINICAL TRIAL REGISTRATION: LIBERTY AD SOLO 1: ClinicalTrials.gov identifier NCT02277743; EudraCT 2014-001198-15. LIBERTY AD SOLO 2: ClinicalTrials.gov identifier NCT02277769; EudraCT 2014-002619-40. LIBERTY AD OLE: ClinicalTrials.gov Identifier NCT01949311; EudraCT 2013-001449-15.

Dupilumab treatment induced similar improvements in signs, symptoms, and quality of life in adults with moderate-to-severe atopic dermatitis with baseline Eczema Area and Severity Index Score <24 or ≥24.

BACKGROUND: In multiple phase 3 trials, dupilumab improved signs, symptoms (including pruritus), and quality-of-life (QoL) in adults with moderate-to-severe atopic dermatitis (AD). In Italy, dupilumab received innovation status but is currently only reimbursed by the National Health Service for adults with Eczema Area Severity Index (EASI) scores ≥24. This analysis assesses disease burden and dupilumab efficacy in adults with EASI scores above and below this threshold. METHODS: This post-hoc analysis included 299 adults pooled from two, randomized, placebo-controlled, phase 3 trials, LIBERTY AD CAFÉ (NCT02755649) and LIBERTY AD CHRONOS (NCT02260986), who received the approved dupilumab regimen (300 mg every 2 weeks) or placebo, with concomitant topical corticosteroids. EASI, Peak Pruritus Numerical Rating Scale (PP-NRS), and Dermatology Life Quality Index (DLQI) were assessed in patients with EASI scores ≥20 to <24 and ≥24 at week 16. RESULTS: At baseline, EASI was weakly correlated with PP-NRS and DLQI (Spearman's correlation coefficient: 0.22 and 0.29, respectively). At week 16, in both the EASI<24 and EASI≥24 populations, respectively, significantly more patients vs. control achieved: ≥50% improvement in EASI (95.5% vs. 55.6%; 80.6% vs. 33.1%); ≥3-point improvement in PP-NRS (68.4% vs. 35.3%; 55.3% vs. 17.7%); and ≥4-point improvement in DLQI (83.3% vs. 43.8%; 84.2% vs. 41.9%); from baseline. Dupilumab was generally well tolerated with an acceptable safety profile. CONCLUSIONS: Dupilumab treatment improves signs, symptoms, and QoL in moderate-to-severe AD adults with EASI<24, who can present with high disease burden. Opportunity may exist to use additional parameters to define disease severity and access to new therapies.