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Introduction: There are few long-term effectiveness and safety data for dupilumab in the treatment of atopic dermatitis (AD). The aim of this study was to evaluate efficacy and safety of dupilumab for up to three years after treatment initiation. Materials and Methods: We collected data from patients ≥ 12 years with severe AD who started dupilumab at the Dermatology Clinic of the Turin University Hospital between December 2018 and October 2022. Clinic and patient reported outcomes were evaluated from baseline, up to 3 years (T9), every 4 months. Results: A total of 418 patients were observed. A progressive decrease in the meanEASI was observed: from 23.64 at baseline to 2.31 at T9. Similar trends were observed in patients' reported outcomes. The achievement of EASI75 and EASI90 was observed in 75.58% of patients and 53.49%, respectively, at T1 (4 months), and in 92.55% and 80.85% at T9; DLQI 0/1 was achieved at T9 in 61.7%. Mean NRSpp ≤ 4 was achieved at T9 in 91.5% (86 out of 94 patients). The most common adverse event was conjunctivitis occurring in 13% of patients on average at each timepoint analyzed. Conclusions: Dupilumab proved to be effective and safe for the treatment of AD in clinical practice, up to 3 years. [ABSTRACT FROM AUTHOR]

According to recent data, the key molecules in the pathogenesis of atopic dermatitis are the cytokines IL-4 and IL-13, which initiate and maintain Th2 inflammation. Targeted therapy with dupilumab inhibits the signaling function of these cytokines by binding to the IL-4Rα subunit, which is part of the IL-4 and IL-13 receptor complexes. The drug is approved for the treatment of patients over 6 years of age with moderate to severe AD. The efficacy and safety of dupilumab have been confirmed by the results of clinical studies. Materials and methods. 27 children with severe AD at the age of 8–18 years were under constant supervision. All patients received systemic treatment with dupilumab, topically used topical glucocorticosteroids (if necessary), emollients (twice a day). Dosing of dupilumab was carried out according to the instructions for the drug. Results. After 26 weeks of complex therapy, 96,3 % of patients achieved an IGA index value of 0/1 and an improvement of 75 % according to the EASI-75 index. The SCORAD index dropped from an average of 78,8 points to 13,7. The average value of total IgE after 6 months decreased by 1518 kU/l. In 2 (7,4 %) patients, conjunctivitis was noted, which was not a reason to discontinue the drug. Conclusion. During treatment with dupilumab, there is a significant decrease in the severity of the main symptoms of atopic dermatitis, including itching, exacerbations.

Introduction: There are few long-term effectiveness and safety data for dupilumab in the treatment of atopic dermatitis (AD). The aim of this study was to evaluate efficacy and safety of dupilumab for up to three years after treatment initiation. Materials and Methods: We collected data from patients ≥ 12 years with severe AD who started dupilumab at the Dermatology Clinic of the Turin University Hospital between December 2018 and October 2022. Clinic and patient reported outcomes were evaluated from baseline, up to 3 years (T9), every 4 months. Results: A total of 418 patients were observed. A progressive decrease in the meanEASI was observed: from 23.64 at baseline to 2.31 at T9. Similar trends were observed in patients’ reported outcomes. The achievement of EASI75 and EASI90 was observed in 75.58% of patients and 53.49%, respectively, at T1 (4 months), and in 92.55% and 80.85% at T9; DLQI 0/1 was achieved at T9 in 61.7%. Mean NRSpp ≤ 4 was achieved at T9 in 91.5% (86 out of 94 patients). The most common adverse event was conjunctivitis occurring in 13% of patients on average at each timepoint analyzed. Conclusions: Dupilumab proved to be effective and safe for the treatment of AD in clinical practice, up to 3 years.

Introduction: Atopic dermatitis (AD) can affect multiple body regions and is especially burdensome when involving exposed skin areas. Rapid, effective treatment of AD across body regions remains an unmet need, particularly for difficult-to-treat areas such as the head and neck area. We investigated the temporal and regional patterns of clinical improvement in AD with the use of abrocitinib, an orally available Janus kinase 1 selective inhibitor under development for the treatment of moderate-to-severe AD. Methods: We performed a post hoc analysis of data from JADE COMPARE, a phase 3, multicenter, randomized, double-blind, double-dummy trial that evaluated the efficacy and safety of abrocitinib 200 mg once daily, abrocitinib 100 mg once daily, dupilumab 300 mg subcutaneous injection every 2 weeks, and placebo in adult patients with moderate-to-severe AD who were concomitantly receiving medicated topical therapy. Assessments included the Eczema Area and Severity Index (EASI) and SCORing Atopic Dermatitis (SCORAD) index. Results: With abrocitinib 200 mg, time to ≥ 75% improvement in EASI (EASI-75) occurred at a median of 29 days across body regions, including the head and neck region. With abrocitinib 100 mg, EASI-75 response was achieved at a median of 30–32 days for the trunk and lower limbs, and at 56–57 days for the head and neck region and upper limbs. With dupilumab, EASI-75 response was achieved at a median of 43 days for the trunk and 57 days for other regions. EASI body region scores significantly improved with abrocitinib 200 mg and 100 mg versus placebo at week 2 (p < 0.0001 for all comparisons). Improvements with abrocitinib were maintained up to week 16. Conclusions: Rapid and persistent improvement in AD across all body regions was observed with abrocitinib treatment. Abrocitinib may be useful in patients with AD that affects difficult-to-treat anatomical areas or who require a rapid response. Trial registration: Clinicaltrials.gov identifier: NCT03720470. Plain Language Summary: Atopic dermatitis (AD) is the most common form of eczema. It is a long-lasting skin disease that often affects multiple body regions. AD may decrease a person's quality of life, especially when it involves skin areas that are visible to others. Quick, effective treatment for AD across multiple body regions is needed, especially in areas that are difficult to treat and/or cosmetically important, such as the head and neck area. Abrocitinib is a medicine taken orally that is being developed to treat moderate-to-severe AD. Researchers analyzed data from a clinical study called JADE COMPARE (Clinicaltrials.gov identifier: NCT03720470). It evaluated the effectiveness and safety of abrocitinib 200 mg taken once daily, abrocitinib 100 mg taken once daily, and placebo (no study medication) plus medicated skin cream in adults with moderate-to-severe AD. Abrocitinib 200 mg and 100 mg significantly improved the extent and severity of AD as assessed by a measure called the Eczema Area and Severity Index (EASI) compared to placebo at week 2. Improvements were maintained for up to 16 weeks. With abrocitinib 200 mg, the time to ≥ 75% improvement in EASI (EASI-75) was approximately 29 days across body regions, including the head and neck region. With abrocitinib 100 mg, this EASI-75 response occurred at approximately 30 to 32 days for the trunk and legs and at 56 to 57 days for the head and neck region and arms. Abrocitinib may be effective in people with AD that affects difficult-to-treat parts of the body or in those who need a fast response. [ABSTRACT FROM AUTHOR]

Introduction: In a 52-week, phase 3 clinical trial (LIBERTY AD CHRONOS) in adult patients with moderate-to-severe atopic dermatitis (AD), dupilumab in combination with topical corticosteroids (TCS) resulted in a significant improvement in overall Eczema Area and Severity Index (EASI) compared with placebo plus TCS. In a post hoc analysis, dupilumab significantly improved the overall extent and severity of AD across four anatomic regions (head and neck, trunk, upper extremities, lower extremities) over 16 weeks. However, as AD severity and presentation may vary by body region, this analysis sought to determine whether there are regional variations in dupilumab efficacy. Methods: Using data from the LIBERTY AD CHRONOS study, we performed a post hoc analysis of the mean percentage change in individual EASI signs (erythema, infiltration/papulation, excoriation, lichenification) from baseline through week 52 across four anatomic regions (head and neck, trunk, upper extremities, lower extremities). Results: Dupilumab plus TCS, compared with placebo plus TCS, significantly improved the severity of all individual AD signs to a similar extent across the four anatomic regions. Significant improvements in each sign were seen early, within the first 2–4 weeks of treatment, and were sustained through week 52 across all regions. Conclusions: In adult patients with moderate-to-severe AD, treatment with dupilumab resulted in rapid and sustained improvement in the signs of AD across all anatomic regions. Trial registration: LIBERTY AD CHRONOS (NCT02260986). [ABSTRACT FROM AUTHOR]

Introduction/Background Atopic dermatitis (AD) is a chronic, recurrent, inflammatory disease characterized by multiple skin manifestations and intense itching that can impact patient quality of life. The effect of upadacitinib (UPA) and dupilumab (DUP) was evaluated in a double-blind, double-dummy, head-to-head phase 3b clinical trial (Heads Up; NCT03738397) of adult patients (age: 18-75 years) with moderate-to-severe AD (Eczema Area and Severity Index [EASI] =16; body surface area =10%; validated Investigator Global Assessment of Atopic Dermatitis (vIGA-AD) =3 at screening and baseline; Worst Pruritus Numerical Rating Scale [WP-NRS] =4 at baseline) randomized 1:1 to UPA 30 mg orally once-daily (N=348) or DUP 300 mg subcutaneous injection every two weeks after a 600 mg loading dose (N=344). Objective The effects of UPA and DUP on skin clearance and itch improvement are reported here. Methods: Skin clearance was assessed by EASI, with response defined as an improvement =75% (EASI75), =90% (EASI90), and 100% (EASI100) from baseline. Itch intensity was assessed daily by WP-NRS up to week 16, then at study visits up to week 24. Weekly WP-NRS scores were analyzed as a 7-day rolling average up to week 16, then at study visits through week 24. Daily WP-NRS scores were analyzed day-to-day through day 28. Mean percent improvement and the proportion of patients achieving clinically meaningful improvement (=4-point improvement from baseline) were evaluated. The proportion of patients achieving a state of no/minimal itch (defined as WP-NRS score of 0/1) was evaluated as a posthoc analysis. Results: EASI75/90/100 response rates were significantly greater with UPA versus DUP at week 16 (UPA = 72.4%/61.6%/28.4%, DUP = 62.6%/40.3%/7.9%; P<0.01 for all comparisons), with greater EASI75 and EASI90 rates observed with UPA as early as week 1 (nominal P<0.05). Mean percent improvement in weekly WP-NRS was significantly greater with UPA versus DUP at week 16 (UPA = 67.8%, DUP= 49.6%; P<0.001), with greater improvement observed as early as week 1 (nominal P<0.001). Daily WP-NRS data showed a greater mean percent improvement with UPA versus DUP as early as day 2, the day after the first dose (UPA = 22.0%, DUP = 4.2%; nominal P<0.001). The proportion of patients that achieved clinically meaningful improvement in weekly WP-NRS was significantly greater with UPA versus DUP at week 16 (UPA = 56.1%, DUP = 36.4%; P<0.001), with greater proportions observed as early as week 1 (nominal P<0.001). Daily WP-NRS data showed a greater proportion of patients achieved clinically meaningful improvement with UPA versus DUP as early as day 2 (UPA = 15.3%, DUP = 3.4%; nominal P<0.001). The proportion of patients that achieved a state of no/minimal itch based on weekly WP-NRS was greater with UPA versus DUP at week 16 (UPA = 35.5%, DUP = 16.2%; nominal P<0.001) and at week 1 (nominal P<0.001). Conclusions: Skin clearance and itch improvement were consistently better with UPA compared with DUP in adult patients with moderate-to-severe AD, with greater improvements observed as early as week 1 for skin clearance and the day following treatment for itch improvement. [ABSTRACT FROM AUTHOR]

Introduction/Background Atopic dermatitis (AD) is a debilitating chronic inflammatory skin disease with fluctuating disease severity that requires long-term control. Patients report that complete or almost complete skin clearance is highly important as a treatment goal. Upadacitinib is a selective oral Janus kinase (JAK) inhibitor with greater inhibitory potency for JAK1 vs JAK2, JAK3, and tyrosine kinase 2. Objectives: In this post-hoc analysis of the upadacitinib phase 3/3b studies, we analyzed the time patients spent in skin clearance response states over 16 weeks with upadacitinib 15 mg (UPA 15) and 30 mg (UPA 30) compared to placebo and dupilumab. Methods: Data were from phase 3/3b multicenter, randomized, double-blinded studies comparing the safety and efficacy of upadacitinib to either placebo (Measure Up 1 and Measure Up 2) or dupilumab (Heads Up) in patients with moderate-to-severe AD. In the Measure Up 1 and Measure Up 2 studies, adults and adolescents were randomized to receive UPA 15, UPA 30, or placebo once daily for 16 weeks. In the Heads Up study, adults were randomized to receive UPA 30 once daily or dupilumab 300 mg every 2 weeks beginning at week 2 following an initial loading dose of 600 mg. The days patients spent in skin clearance response states based on Eczema Area Severity Index (EASI) improvements =75%/90%/100% (EASI 75/90/100) from baseline were assessed. Missing data at study visits were imputed using non-responder imputation. Response states between study visits were interpolated using last observation carried forward. Results: Integrated data from Measure Up 1 and Measure Up 2 included 1683 adults and adolescents randomized to UPA 15 (N=557), UPA 30 (N=567), or placebo (N=559); 44.0% were female, and 48.8% had previously received systemic therapy. In the Heads Up study, 673 adults were randomized to UPA 30 (N=342) or dupilumab (N=331); 44.3% were female, and 52.7% had previously received systemic therapy. Patients in Measure Up 1 and 2 taking UPA 15 or UPA 30 cumulatively spent a greater proportion of days in EASI 75 (UPA 15: 54.2%, UPA 30: 64.6%, Placebo: 10.2%), EASI 90 (UPA 15: 32.0%, UPA 30: 44.0%, Placebo: 3.2%), and EASI 100 (UPA 15: 7.5%, UPA 30: 13.5%, Placebo: 0.6%) response states compared to placebo over 16 weeks. In the Heads Up study, patients taking UPA 30 vs dupilumab cumulatively spent a greater proportion of days in EASI 75 (67.1% vs 44.9%), EASI 90 (47.0% vs 23.2%), and EASI 100 (12.6% vs 3.6%) response states over 16 weeks. Conclusions: Treatment of moderate-to-severe AD with UPA 15 or UPA 30 resulted in a greater proportion of days spent with higher levels of skin clearance (EASI 75/90/100) compared to placebo over 16 weeks, mirroring findings from the Heads Up study comparing UPA 30 to dupilumab. Increases in time spent with high levels of skin clearance with upadacitinib treatment may reflect improved long-term disease control and translate into more time spent experiencing a better quality of life that is less burdened by AD. [ABSTRACT FROM AUTHOR]

This systematic review evaluates the efficacy, safety and economic impact of dupilumab compared to standard of care for uncontrolled moderate‐to‐severe atopic dermatitis (AD). Pubmed, EMBASE and Cochrane Library were searched for RCTs and health economic evaluations. Critical and important AD‐related outcomes were considered. The risk of bias and the certainty of the evidence were assessed using GRADE. Seven RCTs including 1845 subjects >12 years treated with dupilumab 16 to 52 weeks were evaluated. For adults, there is high certainty that dupilumab decreases SCORAD (MD −30,72; 95% CI −34,65% to −26,79%) and EASI‐75 (RR 3.09; 95% CI 2.45 to 3.89), pruritus (RR 2.96; 95% CI 2.37 to 3.70), rescue medication (RR 3.46; 95% CI 2.79 to 4.30), sleep disturbance (MD −7.29; 95% CI −8.23 to −6.35) and anxiety/depression (MD −3.08; 95% CI −4.41 to −1.75) and improves quality of life (MD −4.80; 95% CI −5.55 to −4.06). The efficacy for adolescents is similar. Dupilumab‐related adverse events (AEs) slightly increase (low certainty). The evidence for dupilumab‐related serious AE is uncertain. The incremental cost‐effectiveness ratio ranged from 28 500 £ (low certainty) to 124 541 US$ (moderate certainty). More data on long‐term safety are needed both for children and for adults, together with more efficacy data in the paediatric population. Registration: PROSPERO (CRD42020153645). [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a debilitating chronic inflammatory skin disease with fluctuating disease severity that requires long-term control. Patients report that complete or almost complete skin clearance is highly important as a treatment goal. Upadacitinib is a selective oral Janus kinase (JAK) inhibitor with greater inhibitory potency for JAK1 vs. JAK2, JAK3, and tyrosine kinase 2. In this post-hoc analysis of the upadacitinib phase 3/3b studies, we analysed the time patients spent in skin clearance response states over 16 weeks with upadacitinib 15 mg (UPA 15) and 30 mg (UPA 30) compared to placebo and dupilumab. Data were from phase 3/3b multicenter, randomized, double-blinded studies comparing the safety and efficacy of upadacitinib to either placebo (Measure Up 1 and Measure Up 2) or dupilumab (Heads Up) in patients with moderate-to-severe AD. In the Measure Up 1 and Measure Up 2 studies, adults and adolescents were randomized to receive UPA 15, UPA 30 or a placebo once daily for 16 weeks. In the Heads Up study, adults were randomized to receive UPA 30 once daily or dupilumab 300 mg every 2 weeks beginning at week 2 following an initial loading dose of 600 mg. The days patients spent in skin clearance response states based on Eczema Area Severity Index (EASI) improvements ≥75%/90%/100% (EASI 75/90/100) from baseline were assessed. Missing data at study visits were imputed using non-responder imputation. Response states between study visits were interpolated using the last observation carried forward. Integrated data from Measure Up 1 and Measure Up 2 included 1683 adults and adolescents randomized to UPA 15 (N=557), UPA 30 (N=567), or placebo (N=559); 44.0% were female, and 48.8% had previously received systemic therapy. In the Heads Up study, 692 adults were randomized to UPA 30 (N=348) or dupilumab (N=344); 45.5% were female, and 51.0% had previously received systemic therapy. Patients in Measure Up 1 and 2 taking UPA 15 or UPA 30 cumulatively spent a greater proportion of days in EASI 75 (UPA 15: 54.2%, UPA 30: 64.6%, Placebo: 10.2%), EASI 90 (UPA 15: 32.0%, UPA 30: 44.0%, Placebo: 3.2%), and EASI 100 (UPA 15: 7.5%, UPA 30: 13.5%, Placebo: 0.6%) response states compared to placebo over 16 weeks. In the Heads Up study, patients taking UPA 30 vs. dupilumab cumulatively spent a greater proportion of days in EASI 75 (58.9% vs. 36.9%), EASI 90 (42.1% vs. 19.1%), and EASI 100 (11.8% vs. 3.3%) response states over 16 weeks. Treatment of moderate-to-severe AD with UPA 15 or UPA 30 resulted in a greater proportion of days spent with higher levels of skin clearance (EASI 75/90/100) compared to placebo over 16 weeks, mirroring findings from the Heads Up study comparing UPA 30 to dupilumab. Increases in time spent with high levels of skin clearance with upadacitinib treatment may reflect improved long-term disease control and translate into more time spent experiencing a better quality of life that is less burdened by AD. [ABSTRACT FROM AUTHOR]

The mean global EASI score was 23.6 (±11.88), the EASI of the specific head-neck site (H&N) was 3.2 (±1.9), the trunk EASI was 6.3 (±4.6), the upper limbs EASI was 5 (±3.2) and the lower limbs EASI was 8.8 (±6.5). Keywords: atopic dermatitis; body sites; dupilumab; EASI; head & neck EN atopic dermatitis body sites dupilumab EASI head & neck 1717 1718 2 10/18/21 20211101 NES 211101 Atopic dermatitis (AD) is a chronic inflammatory disease that affects approximately 5-10% of the child population and 3-10% of the adult population worldwide.1 It can affect any part of the body indifferently, having a different distribution of eczematous lesions depending on the patient's period of life; in adults, it is common to see lesions on the neck, limbs and trunk; in particular, some patients report involvement of specific sites such as the head and neck region. [Extracted from the article]