Real-World Characteristics, Treatment Patterns, and Outcomes in Adult Patients Receiving Abrocitinib for Atopic Dermatitis in China: Interim Analysis from the AHEAD Registry.

Relationship between EASI and SCORAD severity assessments for atopic dermatitis

Emerging treatments for moderate-to-severe atopic dermatitis (AD) may provide greater and faster improvement in AD signs and symptoms than current therapies. To examine JADE COMPARE (NCT03720470) data using stringent efficacy end points. Adults with moderate-to-severe AD were randomly assigned 2:2:2:1 to receive oral abrocitinib 200 or 100 mg once daily, subcutaneous dupilumab 300 mg every 2 weeks (600-mg loading dose), or placebo, with medicated topical therapy for 16 weeks. Stringent response thresholds were applied for Eczema Area and Severity Index (EASI), Investigator's Global Assessment, Dermatology Life Quality Index, Peak Pruritus Numerical Rating Scale, and Night Time Itch Scale severity. At week 16, 48.9%, 38.0%, and 38.8% of the abrocitinib 200-mg, 100-mg, and dupilumab groups, respectively, achieved greater than or equal to 90% improvement from baseline in EASI versus 11.3% placebo; 14.9%, 12.6%, and 6.5% achieved Investigator's Global Assessment 0 (clear) versus 4.8% placebo; 29.7%, 21.6%, and 24.0% achieved Dermatology Life Quality Index 0/1 (no/minimal impact on quality of life) versus 10.6% placebo; and 57.1%, 44.5%, and 46.1% achieved Night Time Itch Scale severity 0/1 (no/minimal night-time itch) versus 31.9% placebo. Kaplan-Meier median time to greater than or equal to 90% improvement from baseline in EASI was 59, 113, and 114 days in the abrocitinib 200-mg, 100-mg, and dupilumab groups, respectively, and was not evaluable for placebo; median time to Peak Pruritus Numerical Rating Scale 0/1 (no/very minimal itch) was 86 and 116 days for abrocitinib 200-mg and dupilumab groups, respectively, and was not evaluable for abrocitinib 100-mg and placebo groups. A greater proportion of patients treated with abrocitinib than placebo had almost complete control of AD signs and symptoms.

Head and neck severity index is associated to a significant worsening of quality of life in atopic dermatitis patients.

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

BackgroundTraditional systemic immunosuppressants and advanced therapies improve signs and symptoms of moderate-to-severe atopic dermatitis (AD). However, data are limited in severe and/or difficult-to-treat AD. In the phase 3 JADE COMPARE trial of patients with moderate-to-severe AD receiving background topical therapy, once-daily abrocitinib 200 mg and 100 mg showed significantly greater reductions in the symptoms of AD than placebo and significantly greater improvement in itch response (with abrocitinib 200 mg) than dupilumab at week 2.ObjectiveThis study assessed the efficacy and safety of abrocitinib and dupilumab in a subset of patients with severe and/or difficult-to-treat AD in a post hoc analysis of the JADE COMPARE trial.MethodsAdults with moderate-to-severe AD received once-daily oral abrocitinib 200 mg or 100 mg, dupilumab 300 mg subcutaneous injection every 2 weeks, or placebo with concomitant medicated topical therapy. Severe and/or difficult-to-treat AD subgroups were classified by baseline characteristics [Investigator’s Global Assessment (IGA) 4, Eczema Area and Severity Index (EASI) > 21, failure or intolerance to prior systemic agents (excluding patients who took only corticosteroids), percentage of body surface area (%BSA) > 50, upper quartiles of EASI (EASI > 38) and %BSA (%BSA > 65), and combined subgroup of IGA 4, EASI > 21, and %BSA > 50, and failure or intolerance to prior systemic agents (excluding patients who took only corticosteroids)]. Assessments included IGA score of 0 (clear) or 1 (almost clear) and a ≥ 2-point improvement from baseline, ≥ 75% and ≥ 90% improvement from baseline in EASI (EASI-75 and EASI-90), ≥ 4-point improvement from baseline in Peak Pruritus-Numerical Rating Scale (PP-NRS4), time to PP-NRS4, least squares mean (LSM) change from baseline in 14-day PP-NRS (days 2–15), Patient-Oriented Eczema Measure (POEM), and Dermatology Life Quality Index (DLQI) up to week 16.ResultsThe proportion of patients achieving IGA 0/1, EASI-75, and EASI-90 responses was significantly greater with abrocitinib 200 mg than placebo (nominal p < 0.05) across all subgroups with severe and/or difficult-to-treat AD. Across most subgroups, PP-NRS4 response was significantly greater with abrocitinib 200 mg than placebo (nominal p < 0.01); the time to achieve this response was shorter with abrocitinib 200 mg (range 4.5–6.0 days) than abrocitinib 100 mg (range 5.0–17.0 days), dupilumab (range 8.0–11.0 days), and placebo (range 3.0–11.5 days). LSM change from baseline in POEM and DLQI was significantly greater with abrocitinib 200 mg than placebo (nominal p < 0.001) across all subgroups. Clinically meaningful differences were observed between abrocitinib and dupilumab for most evaluated endpoints across several subgroups, including in patients who failed or were intolerant to prior systemic therapy.ConclusionsAbrocitinib provided rapid and substantially greater improvements in skin clearance and quality of life compared with placebo and dupilumab in subgroups of patients with severe and/or difficult-to-treat AD. These findings support the use of abrocitinib for severe and/or difficult-to-treat AD.Trial registration:ClinicalTrials.gov, NCT03720470.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40257-023-00785-5.

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 &amp;lt;7, &amp;lt;5, &amp;lt;3, and &amp;lt;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&amp;lt;1) and systemic biologic/JAKi-naïve patients (EASI75; EASI&amp;lt;5; IGA 0/1; DLQI/CDLQI &amp;gt;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.

Assessing treatment response is key to determining treatment value in atopic dermatitis (AD). Currently, response is assessed using various clinician- or patient-reported measures and response criteria. This variation creates a mismatch of evidence across trials, hindering the ability of clinicians, regulators, and payers to compare the efficacy of treatments. This review identifies which measures and criteria are used to determine response in clinical trials and health technology assessments (HTAs). Moreover, it systematically reviews the psychometric performance of those measures and criteria to understand which perform best in capturing patient-relevant symptoms and treatment benefits. A scoping review of clinical trials and HTAs in AD identified the following measures for inclusion: the Eczema Area and Severity Index (EASI), the Investigator's Global Assessment (IGA), the Dermatology Life Quality Index (DLQI) and the Peak Pruritus Numerical Rating Scale (PP-NRS). A systematic search was performed in MEDLINE and Embase to identify studies testing the psychometric performance of these measures in adults or adolescents with AD. A lack of consistency in the assessment of response was observed across clinical trials and HTAs. Important gaps in psychometric evidence were identified. No content validations of the EASI and IGA in AD were found, while some quantitative studies suggested that these measures fail to capture itch, a core symptom. The PP-NRS and DLQI performed well. No studies compared the performance of different response criteria. Content validation of the PP-NRS confirmed the importance of itch as a core symptom and treatment priority in AD; however, itch is not well covered in the EASI or IGA. Including the PP-NRS in clinical trials and HTAs will better capture patient-relevant benefit and response. Although various response criteria were used, no studies compared the performance of different criteria to inform which were most appropriate to compare treatments in clinical trials and HTAs.

Background Itch is well-recognized as the universal and most burdensome symptom in atopic dermatitis (AD). Though, little is known about the heterogeneous characteristics of itch in AD. Objectives To examine the heterogeneous characteristics of itch and their associations in AD. Methods A prospective dermatology practice-based study of children and adults with AD (diagnosed by Hanifin-Rajka criteria) was performed using standardized, validated questionnaires and skin examinations. Severity of AD was assessed with Scoring AD (SCORAD), objective-SCORAD, Eczema Area and Severity Index (EASI), Investigator Global Assessment (IGA), worst-itch verbal rating scale (VRS), average-itch VRS, Patient-reported Global Assessment (PtGA), hours spent itching, intensity of itch, and body surface area (BSA). Quality of life (QOL) was measured by the Dermatology Life Quality Index (DLQI). Latent class analysis (LCA) was used to identify dominant clinical patterns of itch-descriptors. The best-fitting model was selected by minimizing the Bayesian and Akaike information criteria. Multivariate logistic regression models were constructed to examine the relationship of latent class membership with AD severity (adjusting for age and gender) or DLQI scores (adjusting for age, gender, and SCORAD). Results Of 489 participants with AD, 307 (62.8%) reported ≥1 itch-descriptor, most commonly stinging (30.1%), painful (24.5%), burning (23.9%), tingling (23.1%), sensitive (21.7%), crawling (20.2%), warm (14.7%), pinprick (13.7%), tight (12.1%), throbbing (11.2%), sharp (9.6%), biting (9.2%), and/or shooting (3.5%). Participants who endorsed one or more of these itch-descriptors had more severe (verbal rating scales for average or worst itch), frequent and extensive itch, and worse overall AD severity (SCORAD, objective-SCORAD, EASI, IGA, PtGA) (all P ≤0.001). All of the itch-descriptors were more likely to be endorsed with increasing severity of itch and AD. LCA identified 3 distinct patterns of itch-descriptors: A) high conditional probabilities for nearly every itch-descriptor; B) intermediate probabilities for burning, crawling, painful, sensitive, stinging, and tingling; C) lowest probabilities for all itch-descriptors. Latent class membership was strongly associated with AD severity; Class A was associated with highest, class B with moderate, and class C with mildest severity of itch and AD (all P &amp;lt;0.0001). Class A (adjusted odds ratio [95% confidence interval]: 12.19 [2.14-231.29]) and B (4.02 [2.25-7.31]) were also associated with higher odds of moderate-severe impairments in DLQI scores compared to Class C, even after adjusting for AD severity. Conclusions Itch is a heterogeneous symptom of AD and can be experienced differently by AD patients. Many patients describe their itch as having qualities of pain (e.g., stinging, burning) and sensory disturbances (e.g., tingling, crawling), and not purely itch. Patients who described their itch using one or more these characteristics had more severe itch and AD and worse QOL. Clinicians caring for patients with AD should recognize the heterogeneous characteristics of itch and their burden on QOL. Future studies are needed to determine whether these distinct characteristics of itch have different underlying mechanisms or responses to therapy.

IntroductionAdults 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.MethodsWe 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.ResultsThis 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.ConclusionDespite 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 RegistrationLIBERTY AD SOLO 1: NCT02277743; LIBERTY AD SOLO 2: NCT02277769.Infographic available for this article.

The Comparison between Objective and Subjective Severity Scores of Atopic Dermatitis

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 &amp;lt;7, &amp;lt;5, &amp;lt;3, and &amp;lt;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&amp;lt;7; EASI&amp;lt;5; DLQI/CDLQI &amp;gt;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.

Background: A monoclonal anti-interleukin-13 antibody, lebrikizumab, has demonstrated favorable efficacy for atopic dermatitis (AD). However, it is unclear whether early responses to lebrikizumab may be maintained for a longer term or whether patients without early responses may achieve delayed responses in real-world clinical practice.Objectives:To evaluate the sustainability of clinical outcomes achieved at week 16 of lebrikizumab plus topical corticosteroids (TCS) treatment for AD through week 48 and the achievement of delayed responses in patients without early clinical outcomes.Methods:This prospective study included 134 Japanese patients with moderate-to-severe AD treated with lebrikizumab plus TCS. Patients who achieved Eczema Area and Severity Index (EASI) 50, EASI 75, EASI 90, EASI 100, Investigator's Global Assessment (IGA) 0/1, or Peak Pruritus Numerical Rating Scale (PP-NRS) 4 at week 16 were evaluated for maintenance rates of respective outcomes, while week 16 nonachievers were evaluated for delayed achievement rates of respective outcomes at weeks 24, 36, and 48.Results:In week 16 achievers, week 48 maintenance rates of EASI 50, EASI 75, EASI 90, and EASI 100 were 100%, 94.9%, 100%, and 87.5%, respectively, while those of IGA 0/1 and PP-NRS 4 were 86.7% and 97.1%, respectively. In week 16 nonachievers, week 48 achievement rates for EASI 50, EASI 75, EASI 90, and EASI 100 were 50.0%, 50.0%, 36.5%, and 3.4%, respectively, and those for IGA 0/1 and PP-NRS 4 were 26.5% and 23.1%, respectively.Conclusion:Improvements of rash and pruritus achieved at week 16 of lebrikizumab plus TCS treatment were mostly sustained through week 48. Some patients without week 16 responses could achieve delayed responses at later time points.

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)

IntroductionDupilumab is approved as first-line systemic treatment for adults/adolescents with moderate-to-severe atopic dermatitis (AD) in Europe and elsewhere owing to its favourable benefit–risk profile. However, systemic non-steroidal immunosuppressants (NSISS) are often used as first-line therapy in clinical practice. Impact of prior therapy with NSISS on dupilumab’s treatment effect vs. control has not been described previously. This study assessed dupilumab’s efficacy vs. control in patients with moderate-to-severe AD, comparing treatment effect in patients with/without prior systemic NSISS therapy, in four phase 3 trials.MethodsThis post hoc analysis included 1553 patients randomized to placebo or dupilumab (300 mg q2w) as monotherapy for 16 weeks, or with concomitant topical corticosteroids (TCS) for 16/52 weeks, from four randomized, double-blind, placebo-controlled, phase 3 trials. Patients were stratified by prior use of systemic NSISS and dupilumab-treated patients were analysed against control groups (treated with placebo or placebo + TCS).ResultsDupilumab-treated patients, regardless of prior treatment with NSISS, achieved a significantly higher percentage reduction from baseline in Eczema Area and Severity Index (EASI), SCORing Atopic Dermatitis (SCORAD), Dermatology life Quality Index (DLQI), and Patient-Oriented Eczema Measure (POEM) vs. control; significantly more achieved EASI score ≤ 7, Peak Pruritus Numerical Rating Scale ≤ 4, POEM ≤ 7, and DLQI ≤ 5 by week 4. These rapid, significant improvements were seen with or without concomitant TCS and sustained through end-of-treatment.ConclusionsDupilumab treatment (monotherapy or + TCS) provides rapid, significant, sustained improvements in signs, symptoms, and quality of life in patients with moderate-to-severe AD compared with control, regardless of prior systemic NSISS use.Clinical Trial RegistrationLIBERTY 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 CHRONOS: ClinicalTrials.gov identifier NCT02260986, EudraCT 2013-003254-24. LIBERTY AD CAFÉ: ClinicalTrials.gov identifier NCT02755649, EudraCT 2015-002653-35.Graphic Supplementary InformationThe online version contains supplementary material available at 10.1007/s13555-021-00558-0.

Background: An anti-interleukin-13 monoclonal antibody, tralokinumab, provided favorable efficacy and safety for atopic dermatitis (AD) in clinical trials. However, its long-term sustainability of early responses and delayed responses is unknown in real world. Objective: This study aimed to assess whether clinical outcomes achieved at week 16 of tralokinumab treatment are maintained through week 48 and whether patients without early outcomes achieve delayed outcomes. Methods: This prospective study included 143 Japanese patients with moderate-to-severe AD who received tralokinumab with topical corticosteroids. Patients who achieved an eczema area and severity index (EASI) 0f 50, EASI 75, EASI 90, EASI 100, investigator's global assessment (IGA) 0/1, or a peak pruritus-numerical rating scale (PP-NRS) 4 at week 16 were evaluated for maintenance rates of each outcome, while week 16 non-achievers were evaluated for later achievement rates at weeks 24, 36, and 48. Results: In week 16, achievers of each outcome, the week 48 maintenance rates of EASI 50, EASI 75, and EASI 90 were 100%; those of EASI 100, IGA 0/1, and PP-NRS 4 were 80.0%, 95.0%, and 90.9%, respectively. In week 16 non-achievers, week 48 achievement rates for EASI 50, EASI 75, EASI 90, and EASI 100 were 53.8%, 76.5%, 48.3%, and 12.5%, and those for IGA 0/1 and PP-NRS 4 were 45.5% and 29.6%, respectively. Conclusions: The improvements of rash or pruritus achieved at week 16 of tralokinumab treatment were mostly sustained through week 48, while some patients without early improvements achieved delayed improvements. These results support the importance of longer-term evaluation of treatment responses.