Real-World Evidence of Effectiveness and Safety of Abrocitinib, Baricitinib and Upadacitinib in Atopic Dermatitis: A Systematic Review and Meta-Analysis.

Introduction While clinical trial data demonstrates the efficacy and safety of upadacitinib (UPA), an oral Janus kinase inhibitor (JAKi) for atopic dermatitis (AD), long-term real-world evidence remains limited. Objectives Our study evaluated the real-world effectiveness and safety of UPA for AD at week 52±6. Methods We conducted a multicenter retrospective review of 3 practices in Canada. Effectiveness endpoints were evaluated at weeks 52±6 and including the following: Investigator Global Assessment (IGA) score of clear or almost clear (IGA 0/1) as well as improvements in Eczema Area and Severity Index (EASI), body surface area (BSA), IGAxBSA, and Dermatology Life Quality Index (DLQI)/Children’s DLQI (CDLQI). Safety was determined via incidence of treatment-related adverse events (AEs). Results A total of 102 patients with AD were included in the analysis; mean age was 44.2 (range: 12-79) years and 52.9% (54/102) were female. Initial UPA doses were 15 mg (UPA15: 41.2%, 42/102) or 30 mg (UPA30: 58.8%, 60/102) once daily. Previous systemic therapies included conventional non-biologics (72.5%), biologics (30.4%), and JAKi (2.9%). At week 52±6: 78.4% (80/102) of patients achieved Investigator Global Assessment (IGA) 0/1; 87.5% (49/56), 78.6% (44/56), and 50.0% (28/56) achieved Eczema Area and Severity Index (EASI) improvements of 75% (EASI75), 90% (EASI90), and 100% (EASI100), respectively; 75.0% (42/56) achieved EASI90 + IGA 0/1; mean EASI was reduced from 12.9 to 0.8 (mean EASI improvement = 91.4%); 91.9% (52/56), 92.9% (52/56), 82.1% (46/56), and 75.0% (42/56) achieved absolute EASI scores <7, <5, <3, and <1, respectively; mean body surface area (BSA) was reduced from 17.0% to 0.6% (mean BSA improvement=87.8%); mean IGAxBSA was reduced from 52.1 to 0.8 (mean IGAxBSA improvement=90.7%); and mean Dermatology Life Quality Index (DLQI)/Children’s DLQI was reduced from 13 to 1.8 (mean DLQI/CDLQI improvement=86%), with 66.0% (33/50) of patients achieving DLQI/CDLQI 0/1. For patients not achieving IGA 0/1, EASI75, EASI90, and EASI100 at weeks 8-20, these responses were subsequently achieved in 60.0% (6/10), 88.9% (8/9), 84.6% (11/13), and 38.1% (8/21) of patients at week 52±6. Dose alterations occurred in 13 patients (12.7%) (escalation: 6.9%, 7/102; reduction: 5.9%, 6/102). Concomitant systemic therapies were used in 1.0% (1/102) of patients. We noted higher statistically significant achievement of endpoints for systemic biologic/JAKi-naïve vs -experienced patients (EASI75; EASI<7; EASI<5; DLQI/CDLQI >4-point improvement). No significant differences in outcomes were identified between dosing regimens. Frequent AEs included: acne (19.6%, 20/102), hypertriglyceridemia (17.6%, 18/102), elevated creatine phosphokinase (13.7%, 14/102), neutropenia (7.8%, 8/102), and transaminitis (7.8%, 8/102). Seven patients (6.8%) discontinued UPA owing to treatment-related AEs, including one case of venous thromboembolism; four patients (3.9%) discontinued UPA due to patient preference, and one patient (1%) discontinued UPA due to lack of efficacy. No serious infections, tuberculosis, major adverse cardiovascular events, gastrointestinal perforation, malignancy, or deaths were observed in 102.5 patient-years of follow-up. Conclusions In contrast to 52-week data from the Measure Up 1/2 and AD Up clinical trials, our results were superior for several outcome parameters (IGA 0/1, EASI90, EASI100, and DLQI 0/1), possibly owing to a patient population with less extensive baseline disease severity. Additionally, we noted similar achievement of these endpoints versus comparable long-term real-world studies. Safety was consistent with existing data, highlighting acne as a common AE (5.3%-20.3% versus 19.6%). Study limitations include its sample size and retrospective nature.

Previous post hoc analyses of randomized controlled trial data demonstrated that more patients with atopic eczema (AE) on Janus kinase (JAK) inhibitors achieve ‘super response’ (defined as total or nearly total clearance of AE) compared with dupilumab. However, there is a lack of head-to-head comparisons between conventional and novel systemic medications in patients with AE achieving super response in a real-world setting. The aim of this analysis was to explore the association between systemic medications used in patients with AE and patients achieving super response in the UK–Irish Atopic Eczema Systemic Therapy Register (A-STAR). A-STAR is a multicentre prospective observational register in the UK and Ireland aimed at evaluating the real-world effectiveness and safety of systemic treatments in AE. Patients in A-STAR who initiated conventional systemics (oral or subcutaneous methotrexate or ciclosporin), dupilumab or a JAK1 inhibitor (abrocitinib or upadacitinib) were included in this analysis. The outcomes assessed were Eczema Area and Severity Index (EASI), Peak Pruritus Numerical Rating Scale (PP-NRS) and Children’s Dermatology Life Quality Index or Dermatology Life Quality Index (C/DLQI). Patients were stratified by the medications prescribed at baseline. Super response was defined as achieving ≥ 90% improvement in EASI (EASI 90), PP-NRS of 0 or 1 (PP-NRS 0/1) and C/DLQI of 0 or 1 (C/DLQI 0/1) at any timepoint during the follow-up (censored at 500 days). Cox regression was used to assess the association between systemic medication exposure and time to achieve super response. Methotrexate was used as a reference medication. Hazard ratios and 95% confidence intervals were estimated. Risk estimates were adjusted for baseline EASI, C/DLQI, PP-NRS, ethnicity, age, sex, education level, age of AE onset, number of prior systemic treatments, concomitant oral corticosteroids and Fitzpatrick skin type. In total 649 patients were included in the analysis. The medications used were methotrexate (n = 157), ciclosporin (n = 48), dupilumab (n = 299) and JAK1 inhibitors (n = 88). The patients’ mean age was 28.7 years (SD 15.6), the mean (SD) baseline EASI was 18.2 (12.3), mean (SD) baseline PP-NRS 6.5 (2.5) and mean (SD) baseline C/DLQI 14.4 (8.1). The results for the Cox regression are summarized in the Table. Using methotrexate as the reference, both dupilumab and JAK1 inhibitors were associated with significantly more patients achieving super response in crude and adjusted models. In conclusion, treatment with dupilumab and JAK1 inhibitors is associated with a higher proportion of patients with AE achieving super response, compared with methotrexate, despite these treatments being mainly used after failure of conventional systemic medication.TableAssociation between novel systemic immunomodulatory medications and achieving super response in patients with moderate-to-severe AE. Data are expressed as the hazard ratio (95% confidence interval) CrudeAdjustedMethotrexate1 (reference)1 (reference)Ciclosporin2.25 (0.59–8.52)2.79 (0.56–13.9)Dupilumab2.20 (1.04–4.69)3.03 (1.23–7.46)JAK1 inhibitors2.75 (1.58–8.36)5.89 (2.09–16.6)

Background:The pathogenesis of atopic dermatitis (AD) involves various mediators, including cytokines and chemokines, which are produced by immune cells, such as dendritic cells and lymphocytes, and non-immune cells, such as epidermal cells. Several mediators, including thymus and activation-regulated chemokine (TARC), are used as biomarkers for AD severity and activity. However, additional local and systemic biomarkers of AD are required.Methods:This study will include 10 male patients with AD and 5 healthy adult males (age range: 20–80 years). The Eczema Area and Severity Index will be used to objectively evaluate the clinical findings. In addition, the severity of eruptions will be assessed on a 5-point scale by scoring symptoms (erythema, edema/papules, oozing/crusting, excoriation, lichenification, and xerosis), and the total intensity will be calculated by adding the symptom scores together. Subjective symptoms will be assessed using a peak pruritus numerical rating scale. Laboratory tests, including measurements of peripheral eosinophil count and serum total immunoglobulin E, TARC, and lactate dehydrogenase levels, will be performed. Using blood samples and extracts of stratum corneum samples obtained by tape stripping, we will conduct an exploratory analysis of protein expression using an antibody array to identify mediators whose levels are significantly altered in patients with AD. After 4 to 8 weeks, blood samples and stratum corneum samples will be collected again from AD patients. Moreover, we will examine whether the candidate proteins can be quantified using enzyme-linked immunosorbent assays.Discussion:This is an important study exploring potential local and systemic biomarkers of AD. The results of this study will be clinically meaningful for the discovery of new biomarkers for diagnosing and assessing the severity of AD.

The main conventional systemic treatments for atopic dermatitis (AD) are methotrexate (MTX) and ciclosporin (CyA). Dupilumab was the first novel systemic agent to enter routine clinical practice. There are no head-to-head randomized controlled trials or real-world studies comparing these agents directly. Network meta-analyses provide indirect comparative efficacy and safety data and have shown strong evidence for dupilumab and CyA. To compare the real-world clinical effectiveness and safety of CyA, dupilumab and MTX in AD. We compared the effectiveness and safety of these systemic agents in a prospective observational cohort study of adult and paediatric patients recruited into the UK-Irish Atopic eczema Systemic TherApy Register (A-STAR). Treatment effectiveness measures included Eczema Area and Severity Index (EASI), Patient-Oriented Eczema Measure (POEM), Peak Pruritus Numerical Rating Scale (PP-NRS), Dermatology Life Quality Index (DLQI) and children's DLQI (cDLQI). The minimum duration of treatment was 28 days and follow-up was 12 months. Adjusted Cox-regression analysis was used to compare the hazard ratios of achieving EASI-50, EASI-75 and EASI-90 over time, and linear mixed-effects models were used to estimate changes in efficacy scores. Treatment safety was assessed by examining adverse events (AEs) at follow-up visits. We included 488 patients (311 adults and 177 children/adolescents) on dupilumab (n = 282), MTX (n = 149) or CyA (n = 57). CyA and MTX were primarily used as the first-line treatment, while dupilumab was mainly a second-line systemic treatment as per UK National Institute of Clinical and Care Excellence (NICE) recommendations. EASI-50, EASI-75 and EASI-90 were achieved more rapidly in the dupilumab and CyA groups compared with MTX. After adjustment for previous severity, the reduction in EASI, POEM, PP-NRS and DLQI was greater for patients treated with dupilumab compared with MTX. In patients with severe disease the reduction in EASI, POEM and PP-NRS was even greater with CyA. The incidence rates of AEs were similar across groups (734, 654 and 594 per 10 000 person-month on CyA, dupilumab and MTX, respectively). This real-world comparison of CyA, dupilumab and MTX in AD suggests that dupilumab is consistently more effective than MTX and that CyA is most effective in very severe disease within 1 year of follow-up.

Effectiveness and tolerance of Janus kinase inhibitors for the treatment of recalcitrant atopic dermatitis in a real-life French multicenter adult cohort

The main conventional systemic treatments for atopic eczema are methotrexate (MTX) and ciclosporin (CIC). Dupilumab was the first novel systemic agent to enter routine clinical practice. There are no head-to-head randomized controlled trials or real-world studies comparing these agents directly. The aim of this study was to compare the real-world clinical effectiveness and safety of CIC, dupilumab and MTX in atopic eczema. We compared the treatment effectiveness and safety of these systemic agents in a prospective cohort study of adult and paediatric patients recruited into the UK-Irish Atopic Eczema Systemic TherApy Register (A-STAR). Treatment effectiveness measures included Eczema Area and Severity Index (EASI), Patient-Oriented Eczema Measure (POEM), Peak Pruritus Numerical Rating Scale (PP-NRS), Dermatology Life Quality Index (DLQI) and children’s DLQI (cDLQI). The minimum duration of treatment was 28 days, and follow-up was 12 months. Adjusted Cox regression was used to compare the hazards of achieving EASI 50, EASI 75 and EASI 90 (≥ 50%, ≥ 75 and ≥ 90% improvement from baseline) over time, and linear mixed-effects models were used to estimate changes in effectiveness scores. Treatment safety was assessed by examining adverse events at follow-up visits. In total, 488 patients were included: 282 on dupilumab, 149 on MTX and 57 on CIC. CIC and MTX were primarily used first line, while dupilumab was mainly used second line. EASI 50, EASI 75 and EASI 90 were achieved more rapidly in the dupilumab and CIC groups compared with MTX (Table). After adjustment for previous severity, the reductions in EASI, POEM, PP-NRS and DLQI were greater for patients treated with dupilumab compared with MTX. In patients with severe disease the reductions in EASI, POEM and PP-NRS were even greater with CIC. Seven of 13 serious adverse events (SAEs) occurred in 7 of 282 (2%) patients on dupilumab, including 1 event that was considered treatment related: a herpes simplex infection. There were 6 of 13 SAEs reported in 6 of 149 (4%) patients on MTX, including 2 events that were considered treatment related: one herpes simplex infection and 1 joint effusion. There were no SAEs reported in the 57 patients on CIC. This real-world comparison of CIC, dupilumab and MTX in atopic eczema suggests that dupilumab is consistently more effective than MTX, and that CIC is most effective in very severe disease within one follow-up year.TableHazard ratios and 95% confidence intervals between treatment groups of patients achieving EASI 50, EASI 75 and EASI 90ComparisonEASI 50EASI 75EASI 90Dupilumab – methotrexate1.31 (0.93–1.85), P = 0.121.55 (1.02–2.36), P = 0.043.04 (1.53–6.04), P = 0.002Ciclosporin – methotrexate2.22 (1.42–3.47), P < 0.0011.97 (1.11–3.50), P = 0.024.24 (1.86–9.62), P < 0.001Ciclosporin – dupilumab1.69 (1.12–2.57), P = 0.011.27 (0.75–2.17), P = 0.381.39 (0.71–2.73), P = 0.33

Introduction Upadacitinib (UPA), an oral, selective Janus kinase inhibitor (JAKi), is approved for moderate-to-severe atopic dermatitis (AD). While its efficacy and safety are supported by clinical trial data1-3, real-world evidence is limited. Objectives Our study evaluated the real-world effectiveness and safety of UPA for AD between weeks 8-20. Methods We conducted a multicenter retrospective review at three practices in Canada. Effectiveness endpoints measured between weeks 8-20 included: Investigator Global Assessment (IGA) score of clear or almost clear (IGA 0/1) and improvements in Eczema Area and Severity Index (EASI), body surface area (BSA), IGAxBSA, and Dermatology Life Quality Index (DLQI)/Children’s DLQI (CDLQI) improvements. Safety was assessed via treatment-related adverse events (AEs). Results A total of 179 patients were included in the analysis. . The mean age was 44.6 ± 17.5 (range: 12-79) years; 53.6% (96/179) were female. Previous treatments included: topicals (100%, 179/179), light (29.1%, 52/179), systemic non-biologics (74.9%, 134/179), and systemic biologics/JAKi (37.4%, 67/179). Initial UPA doses were 15 mg (44.7%, 80/179) or 30 mg (55.3%, 99/179) once daily. At weeks 8-20: 87.2% (156/179) of patients achieved IGA 0/1; 83.3% (85/102), 74.5% (76/102), and 57.8% (59/102) of patients achieved EASI improvements from baseline of 75% (EASI75), 90% (EASI90), and 100% (EASI100), respectively; mean EASI was reduced from 13.4 to 1.0 (p=0.0001; mean EASI improvement = 88.5%); 98% (100/102), 96.1% (98/102), 88.2% (90/102), and 70.6% (72/102) of patients achieved absolute EASI scores <7, <5, <3, and <1, respectively; mean BSA was reduced from 18.2% to 1.1% (p=0.0001; mean BSA improvement=92.2%); mean IGAxBSA was reduced from 60.9 to 2.1 (p=0.0001; mean IGAxBSA improvement=94.7%); and mean DLQI/CDLQI was reduced from 13.6 to 1.4 (p=0.0001; mean DLQI/CDLQI improvement=87.1%), with 75.9% (63/83) of patients achieving DLQI/CDLQI 0/1. UPA monotherapy was utilized in 39.7% (71/179) of cases. Common concomitant therapies included topical corticosteroids (55.3%, 99/179), topical calcineurin inhibitors (6.7%, 12/179), and intramuscular triamcinolone acetonide (2.2%, 4/179). Statistically significantly higher achievement of endpoints was noted for patients using concomitant therapies (EASI75; EASI90; EASI<1) and systemic biologic/JAKi-naïve patients (EASI75; EASI<5; IGA 0/1; DLQI/CDLQI >4-point improvement). Outcomes were not significantly different between dosing regimens. Frequent AEs included: acne (16.2%, 29/179), hypertriglyceridemia (14%, 25/179), elevated creatinine phosphokinase (10.1%, 18/179), herpes simplex virus (6.7%, 12/179), and transaminitis (4.5%, 8/179). Three patients (1.7%) discontinued treatment (myalgia/arthralgia [n=2]; gastrointestinal discomfort [n=1]). No serious infections, tuberculosis, venous thromboembolism, major adverse cardiovascular events, gastrointestinal perforation, or malignancy were observed in 44.7 patient-years of safety follow-up for the treatment period being analyzed. Conclusions Our study included 75.4% (135/179) of patients with follow-up at weeks ≥12 to ≤16. Interestingly, we found more favourable results than Measure Up 1/2 and AD Up clinical trials at week 16 for IGA 0/1, EASI75, EASI90, EASI100, and DLQI 0/1, likely owing to a patient population with less extensive baseline disease severity, while the safety profile was commensurate. Additionally, we noted higher achievement of IGA 0/1, EASI75, and EASI90 endpoints versus similar real-world studies. Study limitations include its retrospective nature and short follow-up duration. Nonetheless, our results support clinical trial findings suggesting UPA is effective and safe for AD.

This is the English version of guidance for the use of oral Janus kinase (JAK) inhibitors in the treatment of atopic dermatitis. Several cytokines, such as interleukin (IL)-4, IL-13, IL-22, IL-31, thymic stromal lymphopoietin, and interferon-γ, are involved in the pathogenesis of atopic dermatitis. As oral JAK inhibitors hinder the JAK-signal transducers and activators of transcription signal transduction routes involved in the signal transduction of these cytokines, they may be effective for the treatment of atopic dermatitis. In Japan, as oral JAK inhibitors for atopic dermatitis, a JAK1/2 inhibitor, baricitinib, expanded its authorized indications for atopic dermatitis in 2020. Consequentially, a JAK1 inhibitor, upadacitinib, also expanded its indications to atopic dermatitis in 2021, followed by new approval of another JAK1 inhibitor, abrocitinib, for the use under the Japanese health insurance system. Physicians who intend to use them should sufficiently understand and comply with contents of guidelines prepared by the Japanese Ministry of Health, Labour and Welfare to promote optimal use of these drugs. In the treatment with oral JAK inhibitors, it is important to sufficiently consider disease factors, treatment factors and patient backgrounds, and share them with patients to choose treatment options. Points to be considered for drug selection include the efficacy and safety of drugs, age of patients, and dosage and administration of the drug. This guidance was developed for board certified dermatologists, who are specialized in the treatment of atopic dermatitis, and for promoting proper use of oral JAK inhibitors, taking into account a variety of factors in individual patients.

IntroductionMolecular targeted therapies, including advanced atopic dermatitis (AD) treatment with Janus kinase 1 inhibitors (JAK1i) and anti-interleukin-13 antibodies (IL-13Ab), are emerging as effective options. However, the predictive biomarkers for treatment responses remain unclear. Therefore, this study compared the short-term efficacy of JAK1i and IL-13Ab and explored relevant biomarkers.MethodsThis retrospective analysis was conducted in 75 patients with moderate-to-severe AD treated at Fukuoka University Hospital. Relevant biomarkers, including eosinophil count and thymus and activation-regulated chemokine (TARC) levels, were measured at baseline and 3 months. Eczema Area and Severity Index (EASI) and Peak Pruritus Numerical Rating Scale (PP-NRS) scores were also assessed.ResultsPatients received JAK1i (n=37; abrocitinib, n=16; upadacitinib, n=21) or IL-13Ab (n=38; lebrikizumab, n=21; tralokinumab, n=17). At 3 months, no significant difference was observed between JAK1i and IL-13Ab in achieving EASI 75 (odds ratio [OR] = 0.83, p=0.76) or in the incidence of adverse events (OR = 1.40, p=0.55). However, JAK1i was associated with higher odds of achieving PP-NRS 4 (OR=9.36, p=0.0063) and PP-NRS 0/1 (OR=34.61, p<0.0001). In the JAK1i group, eosinophil count reduction correlated with EASI improvement (univariate: R=0.525, p=0.0009; adjusted: β = 0.567, p=0.0004). In the IL-13Ab group, TARC reduction correlated with EASI improvement (univariate: R=0.677, p<0.0001; adjusted: β = 0.661, p<0.0001).ConclusionJAK1i showed greater antipruritic effects than IL-13Ab at 3 months, likely due to interleukin (IL)-31 inhibition. Eosinophil count reduction was the most reflective biomarker of JAK1i efficacy, potentially due to IL-5 suppression, whereas TARC improvement was significantly associated with patients’ treatment response to IL-13Ab. These findings highlight the need for further long-term studies.

Introduction In multiple randomized controlled clinical trials, dupilumab demonstrated robust efficacy in patients with moderate-to-severe atopic dermatitis (AD). Long-term effectiveness of dupilumab in real-world AD treatment is one of the main objectives of the ongoing GLOBOSTAD study. Comprehensive data on Asian patients with moderate-to-severe AD treated with dupilumab are limited. Objectives To report patient-reported outcomes and physician-assessed AD clinical measures to evaluate disease characteristics, severity, and treatment effectiveness 1 year after initiating dupilumab treatment in Asian patients. The baseline disease severity and patient demographics have been reported previously1. Methods This 5-year, multinational, multicentre, prospective, observational study (GLOBOSTAD; NCT03992417) included Asian patients ≥12 years-old with moderate-to-severe AD who initiated dupilumab treatment based on country-specific prescribing criteria. Eczema Area and Severity Index (EASI), Scoring Atopic Dermatitis (SCORAD), Patient-Oriented Eczema Measure (POEM), Peak Pruritus Numerical Rating Scale (PP-NRS) and Dermatology Life Quality Index (DLQI) were assessed at baseline, 3 months (± 1 month), 6 months (± 2 months), and 12 months (± 2 months). Data are reported as observed in patients self-reported as Asian for enrolment/safety (N = 204; data cutoff: March 2023) and follow-up (N = 194) populations. Results During the study, EASI (&amp;gt;21 = severe; ≤7 = mild/no disease) score improved from 28.0 (12.1), mean (SD) at baseline to 7.4 (8.5) at 3 months, 5.7 (6.9) at 6 months, and was sustained until the end of observation period, 12 months, at 4.7 (7.1). Similarly, SCORAD (&amp;gt;50 = severe; &amp;lt;25 = mild/no disease) score improved from 61.5 (16.9) at baseline to 25.4 (16.6) at 3 months, 22.5(14.8) at 6 months, and further improved to 18.6 (13.3) at 12 months. During the study, patients also reported early improvements in POEM, mean (SD) from 19.1 (7.3) at baseline to 8.0 (5.8) at 3 months, 7.6 (5.5) at 6 months, and to 7.2 (5.0) at end of observation period (12 months); PP-NRS decreased from 5.7 (2.3) to 2.1 (2.2) to 1.7 (1.8), and to 1.4 (1.7) at 3 months, 6 months, and 12 months respectively; and DLQI improved from 13.2 (7.4) to 4.9 (4.6) to 4.0 (3.8), and to 4.1 (4.0) at 3 months, 6 months and 12 months respectively. Dupilumab-related adverse events were reported in 44 (21.5%) patients while 4 (2.0%) reported dupilumab-related severe adverse events. Conclusion In Asian patients, the initiation of dupilumab treatment led to early improvements in all AD outcome measures, sustained throughout the 1-year observational period. Safety and treatment effectiveness were consistent with overall population.

Atopic dermatitis (AD) prevalence in elderly patients is increasing. Clinically, elderly AD may present with atypical phenotypes, making the diagnosis difficult. Moreover, treatment challenges arise due to treatment-resistance, comorbidities, polypharmacy, and contraindications to existing therapies. Janus kinase (JAK) inhibitors (abrocitinib, baricitinib, upadacitinib) may offer a valuable alternative. However, their use in elderly populations remains unclear, as older patients are often excluded from clinical trials, and several concerns have been raised about their safety in this category of subjects. This study aimed to evaluate the efficacy and safety of JAK inhibitors in elderly patients with moderate-to-severe AD. A 52-week, multicenter, real-life study was performed enrolling patients aged ≥ 60 years affected by moderate-to-severe AD undergoing treatment with JAK inhibitors for at least 16 weeks across 16 dermatological centers in Italy. Disease severity was assessed at baseline, week (W) 4, 16, 24, and 52 using the Eczema Area and Severity Index (EASI), Dermatology Life Quality Index (DLQI), and Pruritus-Numerical Rating Scale (P-NRS). Adverse events (AEs) were recorded at each follow-up. A total of 72 patients met the inclusion criteria [abrocitinib: 13 (18.06%); baricitinib: 6 (8.33%); upadacitinib: 53 (73.61%)]. Of these, 72 (100.0%) achieved W16 follow-up with 33 (45.83%) and 26 (36.11%) subjects reaching W24 and W52, respectively. At baseline, mean EASI, DLQI and P-NRS were 21.22 ± 10.38, 18.21 ± 7.33, and 7.84 ± 1.94, respectively. A significant improvement in all scores was observed starting from W4 [EASI: 4.77 ± 5.07, DLQI: 4.01 ± 3.98, P-NRS: 1.66 ± 1.83 (p < 0.0001 for all)], continuing to improve up to W52 [EASI: 0.81 ± 1.27, DLQI: 0.31 ± 0.63, P-NRS: 0.42 ± 1.03; (p < 0.0001 for all)]. No treatment interruptions or modifications for ineffectiveness or AEs were registered. No statistically significant differences in terms of efficacy and safety were found among the treatment groups. JAK inhibitors demonstrated significant efficacy and an acceptable safety profile in elderly AD patients.

Abrocitinib efficacy and safety in moderate-to-severe atopic dermatitis by race, ethnicity, and Fitzpatrick skin type

One-year real-world clinical effectiveness, safety, and laboratory safety of dupilumab in Japanese adult patients with atopic dermatitis: A single-center retrospective study

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

There are limited approved systemic treatment options for children with atopic dermatitis (AD). Dupilumab is now approved in the United States for patients 6 months and older with moderate-to-severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies. European Medicines Agency is evaluating the use of dupilumab in children aged 6 months through 5 years with severe AD only. To report the efficacy and safety of dupilumab in the subgroup of children aged 6 months to 5 years with severe AD (IGA score = 4) at baseline in the LIBERTY AD PRESCHOOL trial (NCT03346434 part B). Patients aged 6 months to 5 years with inadequately controlled moderate-to-severe AD were enrolled in LIBERTY AD PRESCHOOL (part B), a randomized, double-blind placebo-controlled phase 3 study. Patients were randomized to either dupilumab 200/300 mg every 4 weeks (200 mg if baseline weight 5 to &amp;lt;15 kg, 300 mg if 15 to &amp;lt;30 kg) or placebo for 16 weeks. All patients initiated standardized treatment with low-potency topical corticosteroids (TCS) from day –14. This analysis reports efficacy and quality-of-life endpoints including a 75% reduction from baseline in the Eczema Area and Severity Index (EASI-75), Peak-Pruritus Numerical Rating Scale (PP-NRS), Children’s Dermatology Life Quality Index (CDLQI, for children aged 4 to &amp;lt;6 years), and Infant’s Dermatitis Quality Of Life (IDQOL, for children &amp;lt;4 years) in children with severe AD. Of the total trial population of 162 patients with moderate-to-severe AD, 125 patients with severe AD at baseline were randomized: 63 to the dupilumab + TCS treatment group and 62 to the placebo + TCS treatment group. Baseline demographics were similar. Mean (SD) baseline disease characteristics were also similar between the dupilumab and placebo groups: EASI (38.8 [13.7] vs. 35.4 [12]), body surface area (63.1% [21] vs. 58.9% [21.4]), weekly average PP-NRS (7.6 [1.4] vs. 7.6 [1.6]), CDLQI (17.5 [5.5] vs. 17.8 [6.4]) and IDQOL (18.4 [5.1] vs. 17.4 [5.4]). Dupilumab treatment resulted in a rapid and significant increase in the proportion of patients achieving EASI-75 compared with placebo treatment by week 4 (27% vs. 4.8%; P = 0.0009). By week 16, this improvement was further increased compared with the placebo group (46% vs. 7%; P &amp;lt; 0.0001). At week 16, dupilumab-treated patients had a significantly greater percent reduction from baseline in PP-NRS compared with the placebo group (LS mean (SE)–41.8 [5.4] vs. 0.5 [5.4]; P &amp;lt; 0.0001). Dupilumab also resulted in significant improvement in quality-of-life outcomes compared with placebo (LS mean [SE]) change from baseline to week 16 in CDLQI (−9.1 [1.1] vs. −2.6 [1.2]; P &amp;lt; 0.0001); IDQOL (−9.1 [1.3] vs. −0.6 [1.1]; P &amp;lt; 0.0001). Treatment-emergent adverse events (TEAEs) were reported in 42 (66.7%) patients in the dupilumab group and 45 (73.8%) patients in the placebo group. Most TEAEs were mild to moderate and deemed unrelated to the study drug by the investigator. The most common TEAE was atopic dermatitis in both the dupilumab group (10 [15.9%]) and placebo group (16 [26.2%]). Additionally, TEAEs in the conjunctivitis cluster were reported by 4 (6.4%) patients in the dupilumab group and none in the placebo group. In the placebo group, 3 (4.9%) serious adverse events were reported. No dupilumab-related adverse events were serious or led to treatment discontinuation. Dupilumab significantly improved AD signs, symptoms, and quality of life in children aged 6 months to 5 years with severe AD. The safety profile was consistent with that previously seen in adults, adolescents, and children aged &amp;gt; 6 years of age.