Baricitinib for atopic dermatitis patients who responded inadequately to dupilumab treatment:First daily practice results

Background: Baricitinib is the first JAK inhibitor registered for the treatment of moderate-to-severe atopic dermatitis (AD). Efficacy and safety were shown in clinical trials, but daily practice data is sparse. Objectives: To evaluate the effectiveness and safety of baricitinib treatment in daily practice in AD patients who have inadequately responded to dupilumab. Methods: In this prospective observational cohort study, AD patients who failed dupilumab treatment and started baricitinib treatment in context of standard care at the Erasmus MC (the Netherlands) were included. We analysed physician-reported scores and patient-reported outcome measure scores (PROMs). Results: Twenty-five patients were included. Baricitinib treatment resulted in significant improvement of Eczema Area and Severity Index (EASI) scores and PROMs. Seven patients showed a good and sustained response (EASI50), eight patients showed no response (&lt;EASI50), and five patients showed an initial response but worsening of EASI scores in time. Overall, baricitinib was well tolerated. Four patients discontinued baricitinib treatment due to ineffectiveness or side effects. Conclusions: Baricitinib can be an effective treatment for a subset of AD patients who failed dupilumab treatment in daily practice. We found three different treatment response groups including responders, temporarily responders, and non-responders.</p

Baricitinib for atopic dermatitis patients who responded inadequately to dupilumab treatment:First daily practice results

Background: Baricitinib is the first JAK inhibitor registered for the treatment of moderate-to-severe atopic dermatitis (AD). Efficacy and safety were shown in clinical trials, but daily practice data is sparse. Objectives: To evaluate the effectiveness and safety of baricitinib treatment in daily practice in AD patients who have inadequately responded to dupilumab. Methods: In this prospective observational cohort study, AD patients who failed dupilumab treatment and started baricitinib treatment in context of standard care at the Erasmus MC (the Netherlands) were included. We analysed physician-reported scores and patient-reported outcome measure scores (PROMs). Results: Twenty-five patients were included. Baricitinib treatment resulted in significant improvement of Eczema Area and Severity Index (EASI) scores and PROMs. Seven patients showed a good and sustained response (EASI50), eight patients showed no response (&lt;EASI50), and five patients showed an initial response but worsening of EASI scores in time. Overall, baricitinib was well tolerated. Four patients discontinued baricitinib treatment due to ineffectiveness or side effects. Conclusions: Baricitinib can be an effective treatment for a subset of AD patients who failed dupilumab treatment in daily practice. We found three different treatment response groups including responders, temporarily responders, and non-responders.</p

Upadacitinib treatment in a real-world difficult-to-treat atopic dermatitis patient cohort

Background: Upadacitinib was the first JAK-1 selective inhibitor registered for the treatment of moderate-to-severe atopic dermatitis (AD). Although efficacy and safety have been shown in clinical trials, real-world data on the use of upadacitinib in patients that have been treated with other immunosuppressants and targeted therapies is limited. Objectives: To provide real-world evidence on the use of upadacitinib treatment in moderate-to-severe atopic dermatitis. Methods: In this prospective observational single-centre study, all AD patients treated with upadacitinib treatment in the context of standard care were included between August 2021 and September 2022. Clinical outcome measures and adverse events (AEs) were analysed. Results: Forty-eight patients were included. The majority (n = 39; 81%) had failed (ineffectiveness) on other targeted therapies, including other JAK inhibitors and biologics. Thirty-four (71%) patients were still using upadacitinib treatment at last follow up (median duration 46.5 weeks). Fourteen (29%) patients discontinued treatment due to ineffectiveness or AE. Upadacitinib treatment led to a significant decrease of disease severity during a median follow up of 37.5 weeks. Median IGA at baseline decreased from 3 (IQR 2–3) to 1.5 (IQR 1–2) at last review (p &lt; 0.001). Median NRS itch decreased from 7 (IQR 5–8) at baseline to 2.25 (IQR 0.25–6.5) at last review (p &lt; 0.001). Three patients discontinued treatment due to AE. Forty-eight AEs were reported, including acne-like eruptions (25%), nausea (13%) and respiratory tract infections (10%). Conclusions: In this real-world cohort, we confirmed that upadacitinib is an effective treatment in a subset of AD patients that have failed several previous systemic immunosuppressive and biologic treatments. Overall, AE were mostly well tolerated and not a reason to discontinue treatment for most patients.</p

Clinical and histopathological characterization of paradoxical head and neck erythema in patients with atopic dermatitis treated with dupilumab: a case series

Dupilumab is the first biologic registered for the treatment of atopic dermatitis (AD). We report on seven patients with AD presenting with a paradoxical head and neck erythema that appeared 10–39 weeks after the start of dupilumab treatment. The patients presented with a relatively sharply demarcated, patchy erythema in the head and neck area that showed no or less scaling compared with their usual eczema. Only one patient experienced symptoms of itch and burning, although this was notably different from his pre-existent facial AD. Except for a notable ‘red face’, eczema on other body parts had greatly improved in six of the seven patients, with a mean numerical rating scale for treatment satisfaction of 9 out of 10 at the time of biopsy. Treatment of the erythema with topical and systemic drugs was unsuccessful. Despite the presence of this erythema, none of our patients discontinued dupilumab treatment. Lesional skin biopsies showed an increased number of ectatic capillaries, and a perivascular lymphohistiocytic infiltration in all patients. In addition, epidermal hyperplasia with elongation of the rete ridges was observed in four patients, resembling a psoriasiform dermatitis. Additional immunohistochemical stainings revealed increased numbers of plasma cells, histiocytes and T lymphocytes. Interestingly, spongiosis was largely absent in all biopsies. We report on patients with AD treated with dupilumab developing a paradoxical erythema in a head and neck distribution. Both clinically and histopathologically we found a heterogeneous response, which was most suggestive of a drug-induced skin reaction

Care for children with atopic dermatitis in the Netherlands during the COVID-19 pandemic:Lessons from the first wave and implications for the future

The first wave of the coronavirus disease 2019 (COVID-19) pandemic had an enormous impact on health-care services, including on care provision for children with atopic dermatitis (AD). We investigated the impact of COVID-19 on the care for children with moderate to severe AD at our tertiary outpatient clinic and examined satisfaction with care. We reviewed outpatient records, comparing total number and types of consultations during the first COVID-19 wave (March until July 2020) with the corresponding months of 2019 and 2018. In addition, we conducted a questionnaire-based study investigating the impact of COVID-19 on clinical and psychological symptoms, and satisfaction with care. A total number of 913 consultations (466 individual children) were conducted during the first COVID-19 wave in 2020, while 698 (391 individual children) and 591 consultations (356 individual children) were conducted in 2019 and 2018. The proportion of remote consultations was higher (56.2%) compared to 14.0% in 2019 and 12.7% in 2018. Worsening of AD was reported by 9.7% of caretakers. Overall satisfaction with provided care was high (8.6; interquartile range [IQR] = 7.3–10.0). Caretakers receiving face-to-face consultation were significantly (p = 0.026) more satisfied (9.0; IQR = 8.0–10.0) than caretakers receiving remote consultation (7.9; IQR = 7.0–9.5). The COVID-19 pandemic had an unprecedented impact on care provision for children with AD, particularly on the number of remote consultations. Overall satisfaction with care was high. The impact of COVID-19 on disease severity remained limited. Remote consultations seem to be a useful tool that can be put into practice during the COVID-19 pandemic

Reducing scratching behavior in atopic dermatitis patients using the EMDR treatment protocol for urge: A pilot study

BackgroundItch, and thereby the scratching behavior, is a common complaint in atopic dermatitis. Scratching damages the skin, which in turn worsens the itch. This itch-scratch cycle perpetuates the skin condition and has a major impact on the patient's quality of life. In addition to pharmacological treatment, psychological interventions show promising results in reducing scratching behavior.ObjectivesTo investigate the effect of treatment according the EMDR treatment protocol for urge on scratching behavior of atopic dermatitis patients in a controlled study.MethodsThis study applies a multiple baseline across subjects design. Six patients were randomly allocated to different baseline lengths and all of them started registration of scratching behavior at the same day, using a mobile phone application. Nocturnal scratching was registered by a smart watch application. The total study duration was 46 days and was equal for all patients. Treatment consisted of two sessions using the EMDR treatment protocol for urge. Furthermore, standardized measures were used to assess disease activity, quality of life, and self-control. The nonoverlap of all pairs effect size was calculated for the daily measure data.ResultsOne patient dropped out. Visual inspection suggests that the scratching behavior decreased over time in all patients. Furthermore, a moderate effect size of the treatment is found. During the baseline phase, scratching behavior fluctuated considerably and showed a slight negative trend. Outcomes of disease activity decreased over time and patients' self-control and quality of life improved after treatment. Nocturnal scratching behavior did not change after the intervention.ConclusionThe results of the visual analysis of day time scratching behavior, disease activity, quality of life, and self-control seem promising. These findings pave the way for future research into the effect of the new intervention on other skin conditions suffering from scratching behavior, such as prurigo nodularis

Predicting therapy response to mycophenolic acid using UGT1A9 genotyping: towards personalized medicine in atopic dermatitis

Atopic dermatitis (AD) is a very common chronic inflammatory skin disease requiring long-term treatment. Mycophenolic acid (MPA) is used off-label in treatment of patients with severe AD failing Cyclosporin A (CsA) treatment, however clinical efficacy is observed in only half of the AD patients. In blood, MPA levels are known to have a large interindividual variability. Low MPA exposure and increased enzyme activity correlates with the presence of UGT1A9 polymorphisms. In this retrospective study, 65 adult AD patients treated with MPA were classified as responder or non-responder to MPA treatment. UGT1A9 polymorphisms were determined using PCR. A significantly higher number of UGT1A9 polymorphisms was found in the group that did not respond to MPA treatment. Of the patients that carried a UGT1A9 polymorphism, 85.7% were non-responsive to MPA treatment. This implies that non-responsiveness in AD patients is more likely to occur in carriers of a UGT1A9 polymorphism. In a binary logistic regression analysis the odds ratio (OR) was 8.65 (95% confidence interval: 0.93–80.17). Our results show that UGT1A9 polymorphisms can be used to identify patients with non-responsiveness to MPA. Patients with UGT1A9 polymorphisms might benefit from higher MPA dosage