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A treat-to-target approach was recently developed to guide systemic treatment for adults with atopic dermatitis (AD). Recommendations outlined criteria for a 3-month initial acceptable treatment target and a 6-month optimal target, evaluated using global assessment of patient-reported disease severity, as well as Eczema Area and Severity Index, itch assessed on an 11-point numerical rating scale, Dermatology Life Quality Index, or Patient-Oriented Eczema Measure. Achievement of these targets with once-daily upadacitinib (15 mg and 30 mg) monotherapy was evaluated using integrated adult data from the Measure Up 1 and 2 phase 3 studies. Among the 852 patients treated with upadacitinib 15 mg or 30 mg, the 3-month initial acceptable target was achieved by >80%, >78%, and ≥87% of patients, and the 6-month optimal target was achieved by ≥53%, >61%, and >73% of patients at weeks 2, 16, and 52, respectively. Achievement of all 6 individual criteria for each of the target goals also increased over time. These findings suggest that upadacitinib 15 mg and 30 mg may help improve standards of care in patients with moderate-to-severe AD by achieving 6-month target goals at 16 weeks and as early as 2 weeks for most patients.

Limited daily practice data on the effect of abrocitinib in patients with atopic dermatitis are available. The aim of this multicentre prospective study is to evaluate the effectiveness and safety of abrocitinib in patients with atopic dermatitis treated in daily practice. In a subgroup, the effectiveness of abrocitinib on hand eczema was evaluated. A total of 103 patients from the BioDay registry were included in the study: week 4 (n = 95), week 16 (n = 61) and week 28 (n = 39). At week 28, the Eczema Area and Severity Index (EASI)-50/75/90 was achieved by 81.8%, 57.6%, and 18.2%, respectively, and the weekly average pruritus numerical rating scale ≤ 4 by 62.9%. The effectiveness of abrocitinib was not significantly different between dupilumab non-responders and dupilumab-naïve patients/responders, and between upadacitinib non-responders and upadacitinib-naïve patients/responders. Mean ± standard deviation Hand Eczema Severity Index decreased from 27.4 ± 27.7 at baseline to 7.7 ± 12.1 at week 28 (n = 31). Thirty-two patients (31.1%) discontinued treatment due to ineffectiveness (n = 17), adverse events (n = 9) or both (n = 3). The most frequently reported adverse event was nausea (n = 28). In conclusion, abrocitinib is an effective treatment for atopic dermatitis and can be effective for patients with previous inadequate response to dupilumab or upadacitinib. Furthermore, hand eczema can improve in patients treated with abrocitinib for atopic dermatitis.

Atopic dermatitis is a chronic skin condition for which a range of systemic treatments have recently been approved. A treat-to-target strategy has been developed previously alongside an algorithm to guide the management of patients with atopic dermatitis. Here, we review the strategy and algorithm in the context of the evolving therapeutic landscape, and identify areas for further refinement and development.

Data concerning the economic and humanistic burden in patients with paediatric atopic dermatitis (AD) and their families are scarce. This retrospective study investigated these burdens in paediatric patients with AD using maintenance treatment with topical corticosteroids and/or conventional systemic immunosuppressants. Patient-reported outcomes regarding quality of life, AD severity, and parental work-related impairment were completed at inclusion. Data on healthcare resource utilization and medication prescription were collected retrospectively over the previous 12 months. Patients were categorized into mild, moderate or severe AD, based on Eczema Area and Severity Index score and medication use. Costs per patient per year per AD severity category were calculated. A total of 101 patients (median age 11.0 years (interquartile range 7.5-14.0), 47.5% men) were included, of whom 38 had mild AD, 37 moderate AD, and 26 severe AD. Mean ± standard deviation (SD) total costs patient per year for mild, moderate and severe AD were €1,812 ± €1,280, €2,680 ± €3,127, and €5,861 ±  €3,993, respectively. Highest total direct and indirect costs were found in patients with severe AD, mainly due to higher healthcare and medication costs. Highest humanistic burden was found in patients with moderate AD. For example, the median (interquartile range) Patient-Oriented Eczema Measure score was significantly higher in these patients compared with mild and severe AD (19.0 (15.0-24.0) vs 12.0 (8.8-15.0) and 17.0 (9.5-22.0), respectively). AD in paediatric patients incurs considerable direct and indirect costs, especially in patients with severe AD. The high humanistic burden in patients with moderate AD underlines the need for effective and safe new treatment options for children with AD.

Clinical trials showed that upadacitinib, a selective Janus kinase-1 inhibitor, is effective for treatment of moderate-to-severe atopic dermatitis. However, daily practice studies are limited. This multicentre prospective study evaluated the effectiveness of 16 weeks of upadacitinib treatment for moderate-to-severe atopic dermatitis in adult patients, including those with previous inadequate response to dupilumab and/or baricitinib, in daily practice. A total of 47 patients from the Dutch BioDay registry treated with upadacitinib were included. Patients were evaluated at baseline, and after 4, 8 and 16 weeks of treatment. Effectiveness was assessed by clinician- and patient-reported outcome measurements. Safety was assessed by adverse events and laboratory assessments. Overall, the probabilities (95% confidence intervals) of achieving Eczema Area and Severity Index ≤ 7 and Numerical Rating Scale - pruritus ≤ 4 were 73.0% (53.7-86.3) and 69.4% (48.7-84.4), respectively. The effectiveness of upadacitinib was comparable in patients with inadequate response to dupilumab and/or baricitinib and in patients who were naïve for these treatments or who had stopped such treatments due to adverse events. Fourteen (29.8%) patients discontinued upadacitinib due to ineffectiveness, adverse events or both (8.5%, 14.9% and 6.4%, respectively). Most frequently reported adverse events were acneiform eruptions (n = 10, 21.3%), herpes simplex (n = 6, 12.8%), nausea and airway infections (both n = 4, 8.5%). In conclusion, upadacitinib is an effective treatment for patients with moderate-to-severe atopic dermatitis, including those with previous inadequate response to dupilumab and/or baricitinib treatment.

Atopic dermatitis is a chronic inflammatory skin disorder associated with a heterogeneous presentation and considerable disease burden. Exploring atopic dermatitis treatment patterns and patient benefits could improve disease management and patients' quality of life. This study aimed to describe current and previous atopic dermatitis treatment patterns and patient benefits from those treatments to inform disease management. Data were collected in 10 countries. Adults (n = 1,988) with confirmed moderate-to-severe atopic dermatitis completed a web-based cross-sectional survey. Most patients (86.6%) had body surface area involvement <10%, and therapies used were topical (69.7%), systemic (28.1%), and biologics (2.3%). Most flares were managed by topical monotherapies (73.4%), even in patients with body surface area involvement ≥10%. Treatment expectations were met only partially, or not at all, in 75% of patients. Those with body surface area involvement ≥10% reported lower treatment satisfaction. Overall, this study highlights the unmet medical needs in atopic dermatitis management.

Clinical trials have shown that baricitinib, an oral selective Janus kinase 1/2 inhibitor, is effective for the treatment of moderate-to-severe atopic dermatitis. However, daily practice data are limited. Therefore, this multicentre prospective study evaluated the effectiveness and safety of 16-weeks' treatment with baricitinib in adult patients with moderate-to-severe atopic dermatitis in daily practice. A total of 51 patients from the BioDay registry treated with baricitinib were included and evaluated at baseline and after 4, 8 and 16 weeks of treatment. Effectiveness was assessed using clinician- and patient-reported outcome measurements. Adverse events and laboratory assessments were evaluated at every visit. At week 16, the probability (95% confidence interval) of achieving Eczema Area and Severity Index ≤ 7 and numerical rating scale pruritus ≤ 4 was 29.4% (13.1-53.5) and 20.5% (8.8-40.9), respectively. No significant difference in effectiveness was found between dupilumab non-responders and responders. Twenty-two (43.2%) patients discontinued baricitinib treatment due to ineffectiveness, adverse events or both (31.4%, 9.8% and 2.0%, respectively). Most frequently reported adverse events were nausea (n = 6, 11.8%), urinary tract infection (n = 5, 9.8%) and herpes simplex infection (n = 4, 7.8%). In conclusion, baricitinib can be an effective treatment option for moderate-to-severe atopic dermatitis, including patients with non-responsiveness on dupilumab. However, effectiveness of baricitinib is heterogeneous, which is reflected by the high discontinuation rate in this difficult-to-treat cohort.

Real-world evidence, directly comparing the effectiveness of interleukin (IL)17-inhibitors, IL23-inhibitors, tumour necrosis factor alpha (TNF-α)-inhibitors and an IL12/23-inhibitor in psoriasis, is scarce. The aim of this study was to directly compare the first-year effectiveness of biologic therapies for psoriasis, corrected for confounders. This prospective, multicentre cohort study assessed BioCAPTURE data on etanercept, adalimumab, ustekinumab, secukinumab, ixekizumab, and guselkumab in 1,080 treatment episodes of 700 patients with psoriasis. The course of the mean absolute Psoriasis Area and Severity Index (PASI) and the proportion of patients who achieved PASI90/PASI75 were compared using linear mixed models and mixed logistic regression models respectively, corrected for baseline PASI, biologic naivety, and weight. Patients treated with adalimumab, ustekinumab, secukinumab, ixekizumab, or guselkumab all had a significantly lower mean PASI after 12 months compared with etanercept, and significantly higher overall odds of reaching PASI90 than those treated with etanercept. Patients treated with ixekizumab or guselkumab also had higher probabilities of reaching PASI90 than adalimumab, ustekinumab, and secukinumab. Relative to randomized controlled trials, the proportions of patients who reached PASI90/75 were lower in this real-world study.

This study identified risk factors for the development of dupilumab-associated ocular surface disease in patients with moderate-to-severe atopic dermatitis in a large prospective daily practice cohort. Data from the Dutch BioDay Registry were used to assess the risk of developing dupilumab-associated ocular surface disease, by performing univariate and multivariate logistic regression analyses. A total of 469 patients were included, of which 152/469 (32.4%) developed dupilumab-associated ocular surface disease. Multivariate analysis showed a statistically significant association of the development of dupilumab-associated ocular surface disease with a history of any eye disease (history of self-reported episodic acute allergic conjunctivitis excluded) combined with the use of ophthalmic medication at the start of dupilumab (odds ratio 5.16, 95% confidence interval 2.30-11.56, p < 0.001). In conclusion, a history of any eye disease (history of self-reported episodic acute allergic conjunctivitis excluded) combined with the use of ophthalmic medication at baseline was associated with the development of dupilumab-associated ocular surface disease in patients with atopic dermatitis.

Optimal management of atopic dermatitis requires a comprehensive assessment of response to treatment in order to inform therapeutic decisions. In a real-world setting, successful response to atopic dermatitis treatment is measured by sustained improvements in signs, symptoms, and quality of life. Post-hoc analyses of a 1-year, randomized, double-blinded, placebo- controlled trial (NCT02260986) of dupilumab with concomitant topical corticosteroids in 421 adults with moderate-to-severe atopic dermatitis (of whom 315/106 received placebo/dupilumab (of whom 315 received placebo and 106 received dupilumab) was performed to assess the proportion of responders to dupilumab through a multidimensional composite endpoint. At 6-months, 80.2% of dupilumab-treated vs 40.0% placebo patients (p < 0.0001) achieved improvement in signs (Eczema Area and Severity Index ≤ 7), symptoms (worst itch score ≤ 4), or quality of life (Dermatology Life Quality Index ≤5), representative of minimal/clear atopic dermatitis. All 3 endpoints, indicative of no/minimal atopic dermatitis, were achieved by 44.3% of dupilumab-treated vs 10.2% placebo patients (p < 0.0001) and sustained through 1 year. Dupilumab treatment provided sustained clinically meaningful improvement in signs, symptoms, and quality of life in adults with moderate-to-severe atopic dermatitis.

Dupilumab treatment improves signs, symptoms, and quality of life in patients with moderate-to-severe atopic dermatitis. This study evaluated the impact of dupilumab treatment on absenteeism, presenteeism, and related costs in a large multi-centre cohort of adult patients with difficult-to-treat atopic dermatitis in daily practice. Patients treated with dupilumab participating in the Dutch BioDay Registry reporting employment were included. Absenteeism, presenteeism, and related costs at baseline and during follow-up were calculated using the Work Productivity and Activity Impairment questionnaire. A total of 218 adult patients with moderate-to-severe atopic dermatitis were included. Total work impairment reduced significantly from baseline (35.5%) to week 52 (11.5%), p < 0.001. Median weekly productivity losses reduced significantly from baseline (€379.8 (140.7-780.8)) to week 52 (€0.0 (0.0-211.0), p < 0.001). In this study, dupilumab treatment demonstrated a significant improvement in work productivity and reduction in associated costs in a large cohort of patients with difficult-to-treat atopic dermatitis in daily practice.

Currently no treat-to-target framework to guide systemic treatment in adults with moderate-to-severe atopic dermatitis exists. We sought to reach international consensus through an eDelphi process on a core set of recommendations for such an approach. Recommendations were developed by an international Steering Committee, spanning 3 areas (Guiding Principles, Decision Making, and Outcome Thresholds) and 2 specific time-points; an initial acceptable target at 3 months and an optimal target at 6 months, each based on improvements in patient global assessment plus at least one specific outcome domain. These treat-to-target- orientated recommendations were evaluated by an extended international panel of physicians, nurses and patients. Proposed recommendations were rated using a 9-point Likert scale; for each recommendation, consensus agreement was reached if ≥ 75% of all respondents rated agreement as ≥ 7. Consensus on 16 core recommendations was reached over 2 eDelphi rounds. These provide a framework for shared decision-making on systemic treatment continuation, modification, or discontinuation.

There is a need for unified guidance on the management of ocular manifestations of atopic dermatitis and ocular manifestations associated with dupilumab in the Nordic region (Denmark, Finland, Norway and Sweden). This initiative gathered Nordic dermatologists and ophthalmologists to identify consensus in this area using a modified Delphi process. The initiative was led by a Nordic expert panel who developed a questionnaire that was circulated to a wider group. The results informed an agenda consisting of 24 statements to be voted on using a 5-point Likert scale at a meeting in Copenhagen on 24 April 2019. A facilitator moderated discussion and revised statements according to expert feedback for a second vote when required to reach consensus. Consensus was reached for 23 statements regarding the diagnosis, treatment and referral of these patients, which we hope will improve patient management in the Nordic region.

Dupilumab is approved for uncontrolled moderate-to-severe atopic dermatitis (AD); cyclosporine is approved for severe AD for ≤ 1 year. The efficacy/effectiveness of these treat-ments was compared indirectly. Regression models used pooled patient-level data to estimate response (Eczema Area and Severity Index (EASI) EASI-50/EASI-75 at weeks 12-16 and 24-30) to dupilumab 300 mg every 2 weeks (CHRONOS [NCT02260986]) or cyclosporine (University Medical Center). Models were adjusted for sex, baseline EASI, and thymus and activation-regulated chemokine level. A total of 106 patients received dupilumab (+ topical cortico-steroids; + TCS), and 57 received cyclosporine (+ TCS). Among University Medical Center patients, estimated EASI-50 responders were, dupilumab vs. cyclosporine, 91% vs. 77% (p = 0.038; weeks 12-16), and 96% vs. 67% (p < 0.0001; weeks 24-30); EASI-75 responders were 78% vs. 56% (p = 0.016; weeks 12-16) and 80% vs. 47% (p <0.001; weeks 24-30). Among CHRONOS patients, estimated EASI-50 responders were 90% vs. 74% (p <0.038; weeks 12-16) and 92% vs. 53% (p < 0.0001; weeks 24-30); EASI-75 responders were 75% vs. 52% (p = 0.016; weeks 12-16) and 74% vs. 40% (p <0.001; weeks 24-30), respectively. These results suggest a higher relative efficacy of dupilumab vs. cyclosporine.

Given the introduction of new therapies targeting specific immune pathways for atopic dermatitis (AD), information on the economic burden of AD patients is needed. Direct costs (medication use and healthcare resource utilization) and costs of productivity loss were studied in 90 adult patients with AD indicated for systemic treatment. Costs were calculated for patients with controlled (Investigator Global Assessment (IGA) 0-2) and uncontrolled (IGA 3-5) disease at inclusion. Mean (95% confidence interval (95% CI)) total direct costs were €5,191 (€4,382-6,019) per patient per year (PPY), €4,401 (€3,695-5,215) for patients with controlled AD vs. €6,993 (€5,552-8,406), mean difference €2,593 (€820-4,282) (p=0.014) for patients with uncontrolled AD. Costs of productivity loss were €10,040 (€6,260-14,012) PPY for the total group, €6,886 (€4,188-10,129) PPY for patients with controlled AD vs. €13,702 (€6,124-22,996) for patients with uncontrolled AD, mean difference €6,816 (-€1,638-16,677; p=0.148). Total costs (direct costs+costs of productivity loss) were €15,231 (€11,487-19,455) PPY for the total group, €11,287 (€7,974-15,436) for patients with controlled AD vs. €20,695 (€14,068-34,564), mean difference €9,408 (-€119-19,964) (p=0.077) for patients with uncontrolled AD. Patients with AD using systemic immunosuppressive treatment incur considerable direct costs and costs of productivity loss.

Interleukin 17-antagonist secukinumab demonstrated high efficacy for treatment of psoriasis in randomized controlled trials. However, performance in daily practice may differ from trials. Drug survival is a comprehensive outcome covering effectiveness and safety, suitable for analyses of daily practice. The aim of this study was to evaluate drug survival of secukinumab in a daily practice psoriasis cohort. Data were collected from 13 hospitals. Drug survival was analysed using Kaplan-Meier survival curves, split for reason of discontinuation. In total, 196 patients were included (83% biologic experienced). Overall, 12 and 18 months drug survival of secukinumab was 76% and 67%, respectively, and was mostly determined by ineffectiveness. There was a trend towards shorter drug survival in women and in biologic experienced patients. Thirteen percent of patients experienced at least one episode of fungal infection. This is one of the first studies of drug survival of secukinumab in patients with psoriasis treated in daily practice.

An inpatient treatment and education programme has been developed for patients with difficult to control atopic dermatitis (AD), with the aim of achieving adequate self-management and long-term disease control. This observational study included adult patients diagnosed with difficult to control AD, admitted for a structured inpatient treatment and education programme. The primary outcome was the Six Area, Six Sign Atopic Dermatitis (SASSAD) score. In total, 79 patients (mean ± SD age 38.8 ± 17.1 years) were included. The median duration of hospitalization was 11 days (interquartile range 8-14). The mean percentage decrease in SASSAD score between admission and discharge was 60.7%, of which 64 (81.0%) patients achieved SASSAD50. The mean percentage decrease in SASSAD score was 69.0% during follow-up, of which 63 (79.7%) patients still had a SASSAD50. In the majority of these patients with difficult to control AD the admission resulted in sustained disease control. This could be achieved by optimization of treatment with topical corticosteroids.

Safety data with respect to kidney function during long-term treatment with cyclosporine A (CsA) in patients with atopic dermatitis is limited. Data on serum creatinine levels before, during and after CsA treatment were collected in a retrospective cohort of adult patients with atopic dermatitis. The median duration of treatment of 150 patients was 280 days (interquartile range 203-528 days). There was a significant, but not clinically relevant, increase in serum creatinine compared with the baseline level after 3 weeks of treatment with CsA and stabilization during the maintenance phase at the group level. Twenty-two (14.7%) patients had a greater than 30% increase in serum creatinine (cut-off point for clinically relevant change) compared with baseline. These patients were significantly older than the patients without a 30% increase (mean ± standard deviation age 41.4 ± 15.6 vs. 33.8 ± 11.7 years (p = 0.01)). During follow-up, all patients had a less than 30% increase in serum creatinine levels compared with baseline levels. At the group level serum creatinine levels during follow-up were not significantly different from baseline.