Short-, mid- and long-term efficacy of dupilumab in moderate to severe atopic dermatitis: a real life multicenter Italian study on 2576 patients.

BACKGROUND: The efficacy and safety of dupilumab in atopic dermatitis (AD) have been defined in clinical trials but limited real-world evidence on long term treatment outcomes are currently available to inform clinical decisions. OBJECTIVES: to describe long-term effectiveness and safety of dupilumab up to 48 months in patients with moderate-to-severe AD. METHODS: a multicenter, retrospective, dynamic cohort study was conducted to assess long term effectiveness and safety of dupilumab in patients with moderate to severe AD in a real-world setting. Predictors of minimal disease activity (MDA) optimal treatment target criteria (defined as the simultaneous achievement of EASI90, itch NRS score ≤1, sleep NRS score ≤1 and DLQI ≤1) were investigated. RESULTS: 2576 patients were enrolled from June 2018 to July 2022. MDA optimal treatment target criteria were achieved by 506 (21.91%), 769 (40.63%), 628 (50.36%), 330 (55.37%) and 58 (54.72%) of those that reached 4, 12, 24, 36 and 48 months of follow-up, respectively. Logistic regression revealed a negative effect on MDA achievement for conjunctivitis and food allergy at all timepoints. Adverse events (AE) were mild and were observed in 373 (15.78%), 166 (7.02%), 83 (6.43%), 27 (4.50%) and 5 (4.55%) of those that reached 4, 12, 24, 36 and 48 months of follow-up. Conjunctivitis was the most frequently reported AE during the available follow-up. AE led to treatment discontinuation in <1% of patients during the evaluated time periods. CONCLUSION: High long-term effectiveness and safety of dupilumab were confirmed in this dynamic cohort of patients with moderate to severe AD, regardless of clinical phenotype and course at baseline. Further research will be needed to investigate the effect of Th2 comorbidities and disease duration on the response to dupilumab and other newer therapeutics for AD.

Which Factors Are Associated with Persistence of Depressive and Anxiety Symptoms in Patients Affected by Atopic Dermatitis despite 2-Year Treatment with Dupilumab?

Background: Atopic Dermatitis (AD) is a prevalent inflammatory skin disease whose course is often complicated by the presence of concomitant anxiety and depressive disorders. Dupilumab has been demonstrated to be largely effective in AD. The aims of the present study were to (1) to verify the effectiveness of 2-year dupilumab treatment on the depressive and anxiety symptoms of patients affected by AD and (2) to identify predictors of the persistence of psychiatric symptoms despite maintenance treatment with dupilumab. Methods: A total of 331 patients with severe AD were assessed at baseline and at different times over 2 years by a large set of rating scales, including the Eczema Area and Severity Index (EASI), the Hospital Anxiety and Depression Scale (HADS), and the Dermatology Life Quality Index (DLQI). Paired sample t-tests were performed to verify the effectiveness of dupilumab on the severity of AD and mental health items. Two binary logistic regression models were then used to identify the predictors of the persistence of clinically significant depression and anxiety, defined by a score ≥ 8 on each sub-scale of the HADS. Results: After 2 years of treatment with dupilumab, the patients benefited, showing a significant improvement in both the dermatological disease and comorbid depression/anxiety (p < 0.001 for all scales). Overall, 17.5% and 13% of patients, respectively, reported residual depressive and anxiety symptoms after the 2-year treatment with dupilumab. The baseline predictors of the persistence of clinically significant depressive symptoms after the 2-year treatment with dupilumab were found to be a higher body mass index (BMI) (p = 0.012), a lower impact of dermatological disease on quality of life (p = 0.015), and more severe depressive symptoms (p < 0.01), while for anxiety, the only predictor was found to be female gender (p = 0.03). Conclusions: Using a multidisciplinary approach, at baseline, dermatologists should more closely monitor patients who are at a greater risk of maintaining residual psychiatric symptoms despite therapy, such as those with more severe depressive symptoms and those who are overweight.

Assessment of Patient-Reported Outcomes at 48 Months of Treatment with Dupilumab for Severe Atopic Dermatitis: A Single-Center Real-Life Experience with 126 Patients.

BACKGROUND: The main objective was to analyze patient-reported outcomes (PRO) trends over a four-year period in severe atopic dermatitis (AD) patients treated with dupilumab. METHODS: data from 126 severe patients receiving dupilumab for at least 48 months were collected. The clinical scores assessed included the Eczema Area and Severity Index (EASI), Pruritus Numerical Rating Scale (NRS), Sleep NRS, Patient-Oriented Eczema Measure (POEM), Dermatology Life Quality Index (DLQI), and Atopic Dermatitis Control Tool (ADCT). RESULTS: the study compellingly demonstrates dupilumab's effectiveness in reducing EASI and improving PROs, with sustained enhancements observed beyond the initial twelve months of treatment. Univariate and multivariate regression analyses show that baseline factors do not significantly increase the risk of adverse outcomes related to Pruritus NRS, POEM, or ADCT at T48. The robust correlation between ADCT and other PROs suggests closely aligned changes. CONCLUSION: Dupilumab's benefits endure beyond the first year, emphasizing its long-term efficacy, and consistently improves AD outcomes regardless of individual characteristics or clinical variables. ADCT appears to be a practical and versatile tool for the streamlined assessment of AD treatment outcomes.

Mental health in patients affected by atopic dermatitis: which effects of treatment with dupilumab?

Atopic dermatitis (AD) is an inflammatory skin disease. Patients with AD are prone to develop anxiety and mood disorders. Aim of this study is to investigate if treatment with dupilumab may improve mental health status of patients affected by AD. A total of 66 patients with severe AD were included: 24 subjects were candidate or have just started (one month) treatment with dupilumab, and 42 have been in treatment for one year. 25.8%, 30.3%, and 45.5% of the total sample showed, respectively, clinically significant anxiety, depression, and symptoms of Internet addiction. Patients with anxiety symptoms resulted to have more severe AD, more sleep problems ( P  = 0.028), less quality of life ( P  = 0.001), more severe depressive symptoms ( P  < 0.001), to be more frequently women ( P  = 0.016), to be less frequently treated with dupilumab for one year ( P  = 0.025). Similarly, patients with clinically significant depressive symptoms resulted to have more severe AD, more sleep problems ( P  = 0.003), less quality of life ( P  < 0.001), more severe anxiety symptoms ( P  < 0.001), to be less frequently treated with dupilumab for one year ( P  = 0.008). Patients with AD treated for one year with dupilumab showed a better mental health profile in terms of less severe anxiety and depression with respect to their counterparts.

Predictive Factors of Early Response to Dupilumab in Patients with Moderate-to-Severe Atopic Dermatitis.

Efforts have been made to identify factors influencing clinical response in patients with atopic dermatitis (AD) treated with dupilumab. A retrospective single-center observational study was carried out by analyzing data from 492 patients aged 12 years and older with moderate-to-severe AD. The study aimed to identify baseline demographic and clinical factors that could predict the achievement of a mild level of disease, i.e., an Eczema Area and Severity Index (EASI) ≤ 7, within 4 weeks from dupilumab initiation. Classic, generalized lichenoid and inflammatory phenotypes compared with a nummular eczema phenotype (OR = 6.9, 95% CI 2.04-23.48 and OR = 4.22, 95% CI 1.22-14.66, respectively) and a baseline EASI ≤ 24 and between 24-29, compared with a baseline EASI ≥ 29 (OR = 3.1, 95% CI 1.81-5.41 and OR = 1.8, 95% CI 1.05-3.07, respectively), were found to be predictive factors of early response to dupilumab, highlighting the importance of early biological treatment of AD.

Asthma improvement in patients treated with dupilumab for severe atopic dermatitis.

Introduction: Atopic dermatitis (AD) is considered a systemic type 2 immune driven disease, and it is associated to many atopic comorbidities including asthma. The aim of our study was to prospectively evaluate the respiratory outcomes in patients with persistent allergic asthma treated with dupilumab due to severe AD (sAD). Methods: We enrolled eligible patients with sAD for dupilumab treatment from September 2018 to December 2020. We then selected the subgroup of patients sensitized to perennial allergens. Dupilumab's efficacy and safety on AD and comorbid asthma were assessed at baseline, one month, four months, and then every 4 months up to one year. Results: A total of 437 patients with sAD were enrolled for dupilumab treatment due to sAD, and 273 reached 48 weeks of therapy. Respiratory outcomes were evaluated in the 85 asthmatic patients with positivity only to perennial allergens. Our patients showed statistically and clinically significant improvement in asthma control (Asthma Control Test and Asthma Control Questionnaire) and airway obstruction parameters (FEV1), in addition to the expected AD-related skin outcomes. Specifically, a significant improvement was achieved at the fourth month of dupilumab therapy, and this trend was maintained up to twelve months, regardless of asthma severity. Conclusions: Our results showed the overall improvement of the clinical picture that dupilumab offers for patients with severe AD and persistent allergic asthma of any severity, highlighting the importance of a global multidisciplinary approach of type 2 driven disease.

Emerging Systemic Treatments for Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic or chronically relapsing inflammatory skin disease which results from a complex, multifaceted interaction between environmental factors in genetically predisposed patients. Epidermal barrier impairment, alteration of the cutaneous microbiota, effect of external antigens, neurosensory dysfunction, and inflammatory and immune dysregulation all play a pivotal role in inducing and maintaining AD lesions. AD significantly impacts the patient's quality of life and general well-being and is often associated with anxiety and/or depressive symptoms. Classical treatment options include topical corticosteroids and calcineurin inhibitors, phototherapy, and systemic immunosuppression with oral corticosteroids, cyclosporine, methotrexate, and azathioprine in more severe cases. A turning point in facing AD was accomplished when the efficacy and safety of dupilumab, a monoclonal antibody targeting the interleukin (IL)-4 receptor α subunit, led to its approval for the treatment of moderate-to-severe or severe AD in children, adolescents, and adults. Subsequently, a more extensive understanding of AD etiology and pathogenesis has allowed the development of several topical and systemic novel therapy options. Most of these drugs are monoclonal antibodies which interfere with the type 2 inflammatory cascade, especially its key cytokines IL-4 and IL-13, or its downstream Janus kinase signaling pathway. However, considering the relevance of other subtypes of T helper (Th) cells, such as Th1 and Th22, and the important role of specific cytokines (IL-31) in generating pruritus, the horizon of potential therapeutic targets has widened extremely. In this review, we aim to present the most promising systemic agents currently under investigation and illustrate the most significant aspects of their efficacy, safety, and tolerability.

Elevation of peripheral blood eosinophils during dupilumab treatment for atopic dermatitis is associated with baseline comorbidities and development of facial redness dermatitis and ocular surface disease.

INTRODUCTION: Transient eosinophilia is not uncommon in patients with moderate-to-severe atopic dermatitis (AD) treated with dupilumab. METHODS: A retrospective, single center, observational study was conducted to assess the difference in terms of absolute eosinophil count (AEC) change at 4 months and at 12 months, relative to the baseline, in predefined subgroups of patients affected by moderate-to-severe AD treated with dupilumab. RESULTS: Complete data for 373, 289 and 210 patients were available at the baseline, 4 months and 12 months, respectively. Patients with a history of conjunctivitis (n = 152) had greater increases in AEC at 4 months as compared with those (n = 137) who did not (+16%vs0%,p = 0.01). Patients with food allergies (n = 46) showed similar increases (+39%vs + 5%, p = 0.01). Patients experiencing facial redness dermatitis on dupilumab (n = 46) had greater increases in AEC at 4 months than those (n = 243) who did not (+40%vs + 5%, p = 0.03). Patients that had dupilumab-induced ocular surface disease (n = 44) had greater increases in AEC at 4 months than those (n = 245) who did not (+43%vs + 5%, p = 0.01). CONCLUSIONS: Atopic comorbidities are associated with a paradoxical increase in AEC at 4 months in AD patients treated with dupilumab. Patients experiencing dupilumab-related ocular surface disease or facial redness dermatitis also have remarkable increases in AEC at 4 months.

Remission of Alopecia Universalis after 1 Year of Treatment with Dupilumab in a Patient with Severe Atopic Dermatitis.

Alopecia areata (AA), an autoimmune disease with a relapsing-remitting course, represents the second cause of non-scarring alopecia worldwide and is associated with several comorbidities, notably atopic dermatitis (AD). In particular, AD is related to its more severe forms alopecia totalis (AT) and alopecia universalis (AU) [Nat Rev Dis Primers. 2017;3:17011]. Considering that AA has been classified as T helper 1-driven disease, whereas AD is the prototypical T helper 2 (Th2)-driven skin disorder, recent studies suggest that these forms may underlie a different chemokine expression resulting in a Th2 skewing as a key pathomechanism that could explain this association [JAMA Dermatol. 2015 May;151(5):522-8]. Several reports showed that dupilumab, a fully human monoclonal antibody targeting the interleukin 4α receptor and thus downregulating Th2 response, led to an improvement of AA associated with AD; most of these patients were females with AT or AU, early-onset AD, and atopic comorbidities [Exp Dermatol. 2020 Aug;29(8):726-32]. We report here a case to further support this hypothesis.

Skin barrier status during dupilumab treatment in patients with severe atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a common chronic-relapsing inflammatory skin disease hallmarked by epidermal barrier dysfunction, increased transepidermal water loss (TEWL) and decreased skin hydration. Recent findings on the T helper 2 (Th2)-driven pathogenesis of AD have led to the development of dupilumab, a monoclonal antibody directed against interleukin-4 and interleukin-13 that has been demonstrated to be effective in the treatment of moderate-to-severe AD. The effect of dupilumab on skin barrier dysfunction, however, has not yet been adequately investigated. OBJECTIVES: The primary endpoint of this study was to assess the status of the skin barrier in nonlesional skin of patients with severe AD treated with dupilumab, by evaluating the association between the relative variation of TEWL and the achievement of a 75% reduction of EASI (EASI75) over time. METHODS: TEWL was measured below the antecubital fossae by means of the Vapometer® at baseline, at week 4 (T4), at week 16 (T16) and at week 32 after dupilumab starting. EASI and NRS-itch were measured at the same time points. RESULTS: Seventy-eight patients with severe AD treated with dupilumab were enrolled. Median TEWL relative variation respect to baseline was significantly higher in patients who achieved EASI75 as compared with those who did not achieve EASI75 at T16 and at T32, but not at T4. CONCLUSION: During dupilumab treatment, TEWL on nonlesional skin tends to significantly improve 4 months after treatment initiation and could be a good tool for monitoring response to therapy.

Factors Associated with Affective Symptoms and Quality of Life in Patients with Atopic Dermatitis.

The aim of this study was to detect demographic and clinical factors associated with affective symptoms and quality of life in patients with severe atopic dermatitis. First, one-way analyses of variance and correlations were performed to compare a large set of qualitative and quantitative clinical variables. Three final multivariable regression models were performed, with depression/anxiety subscales and Dermatology Life Quality Index scores as dependent variables, and the factors that were statistically significant on univariate analyses as independent ones. More severe anxiety symptoms and poorer quality of life (p < 0.01) were significantly associated with more severe depressive symptoms. Female sex and disturbed sleep (p = 0.03) were significantly associated with more severe anxiety. Finally, previous treatment with cyclosporine (p = 0.03) or methotrexate (p = 0.04), more severe depressive symptoms (p < 0.01), itch (p = 0.03), impaired sleep (p < 0.01) and perceived severity of dermatological illness (p < 0.01) were significant predictors of low quality of life. This study shows a complex interplay between the severity of atopic dermatitis, poor quality of life and presence of clinically relevant affective symptoms. These results will help dermatologists to identify patients who need psychiatric consultation within the framework of a multidisciplinary approach.

Efficacy of Dupilumab on Different Phenotypes of Atopic Dermatitis: One-Year Experience of 221 Patients.

BACKGROUND: The clinical features of adult-onset atopic dermatitis (AD) are heterogeneous and the diagnosis can be a challenge. A new biologic drug (dupilumab) has been approved for moderate to severe AD in adult patients. The efficacy and safety have been demonstrated in clinical trials, but these studies do not reflect conditions in daily practice and do not consider the different clinical manifestations of AD. OBJECTIVES: Analyzing the dupilumab activity in a real-world setting and comparing its efficacy on different AD phenotypes. METHODS: We retrospectively evaluated 221 AD patients treated with dupilumab, stratified into six clinical phenotypes: classic, generalized eczema inflammatory and lichenoid patterns, prurigo, nummular eczema, and erythroderma. At baseline and at weeks 4, 16, and 52, the disease severity was assessed through the Eczema Area and Severity Index (EASI) and the quality of life was assessed through the Dermatology Life Quality Index (DLQI) questionnaire, Peak Pruritus Numerical Rating Scale (itch NRS), and Peak Sleep NRS. RESULTS: We found a significant improvement after 16 weeks of treatment (p < 0.0001) in all six phenotypes for all the assessed scores mentioned above, persisting up to week 52. The best improvement was seen in the more severe phenotypes, particularly the erythrodermic one. CONCLUSIONS: The present study confirmed the efficacy and safety of dupilumab in the treatment of severe AD. Its strength was in the stratification of AD patients in six different phenotypes based on their clinical presentation, all of whom markedly improved in terms of both clinically evident and reported symptoms, as well as their quality of life.

Effectiveness of dupilumab for the treatment of nummular eczema phenotype of atopic dermatitis in adults.

Nummular eczema (NE) is currently considered as one of the clinical phenotypes of atopic dermatitis (AD) of the adult. In this multicentre study, 30 adult patients (age ≥ 18 years) affected with nummular-like AD were treated with dupilumab, a monoclonal antibody against the receptor for interleukin(IL)-4 and IL-13. The evaluation of the results after 16 weeks of treatment showed a significant improvement of the disease, as demonstrated by reduction in Eczema Area Severity Score (EASI), visual analogue score (VAS) of pruritus, and Dermatology Life Quality Index (DLQI) scores. Conjunctivitis in one patient was the only side effect. In conclusion, dupilumab seems to be an effective and safe treatment in NE phenotype of AD of the adult.

Clinical Response and Quality of Life in Patients with Severe Atopic Dermatitis Treated with Dupilumab: A Single-Center Real-Life Experience.

Dupilumab is an anti-interleukin-4 receptor monoclonal antibody that was recently approved for the treatment of atopic dermatitis (AD). In this single-center retrospective study, clinical baseline data of 117 severe AD patients treated with dupilumab were collected. At baseline and at weeks 4 and 16, disease severity was assessed through the Eczema Area and Severity Index (EASI) and quality of life through the Dermatology Life Quality Index (DLQI) questionnaire, Patient-Oriented Eczema Measure (POEM), Hospital Anxiety and Depression Scale (HADS), Peak Pruritus Numerical Rating Scale (NRS-itch), and VAS-sleep. Response to dupilumab was defined as an improvement of ≥75% in EASI from baseline (EASI75). At multivariate analysis, AD onset before 18 years [OR, 2.9; 95% CI, 1.2-7.2; p = 0.0207] and absence of hypereosinophilia [OR, 2.24; 95% CI, 1.03-4.86; p = 0.0412] were identified as significant predictive parameters for response to dupilumab in terms of EASI75 at week 4 but not at week 16. Significant reductions in EASI, DLQI, POEM, HADS, NRS-itch, and VAS-sleep were found between week 4 versus baseline (p < 0.0001 for all) and week 16 versus baseline (p < 0.0001 for all). Early AD onset and absence of hypereosinophilia may be suggested as predictive markers of early response to dupilumab. We confirmed the efficacy and safety of this agent along with the improvement of life quality in severe AD patients.

What Italians think about acne: results of a survey on 2327 acne patients and their mothers.

BACKGROUND: The psychological impact of acne is comparable to that experienced by patients with severe diseases; however, most of the people does not consider acne as a true disease. We evaluated beliefs, sources of information and knowledge about acne in Italian adolescents and their mothers. METHODS: This survey was carried out in 2327 acne patients and their mothers (4654 subjects) by means of a self-administered questionnaire. The questionnaire was based on ten questions: seven questions for the patients and three questions for their mothers. RESULTS: All the 2327 patients and their mothers completed the survey. Approximately 75% of patients declared that acne has a negative influence on their self-esteem and relationships; furthermore, 87% of patients stated that acne limits their social life. Finally, 65% of patients declared that they are under treatment, but only in 20% of cases the treatment was prescribed by a dermatologist. The mothers considered pollution, wrong diet and hyperseborrhea as the most important etiological factors. They considered the treatment suggested by a cosmetologist and contraceptive pill as the best one; only 8% of mothers reported that they regularly took their children to the dermatologist. CONCLUSIONS: In order to improve the treatment and the quality of life in acne patients, there is a need to improve awareness about this disease and its causes and to highlight the role and importance of dermatologists.