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

Tralokinumab treatment for patients with moderate-to-severe atopic dermatitis in daily practice

BACKGROUND: Evidence about tralokinumab treatment for moderate-to-severe atopic dermatitis (AD) in daily practice is limited. AIM: To report the first evidence, to our knowledge, from daily practice of treatment with tralokinumab in patients with AD. METHODS: In this observational prospective study, patients with AD who received tralokinumab treatment in the context of routine care at the Erasmus Medical Centre were included between November 2021 and February 2022. This included 28 patients who had previously been treated with dupilumab, and 14 patients who had been treated with a Janus kinase inhibitor (JAKi). The Investigator's Global Assessment (IGA; 0-4) and the numeric rating scale peak pruritus during the past 7 days (NRS itch 7d: 0-10), adverse events and reasons for discontinuation were analysed. A good clinical response was defined as any decrease in IGA and NRS itch 7d and if a patient was satisfied with the treatment and wished to continue with therapy. RESULTS: In total, 37 patients were treated with tralokinumab. Twenty-two (59%) patients showed a good response to tralokinumab treatment. Fifteen (41%) patients discontinued treatment because of inadequate AD control or adverse events. Treatment-related adverse events were mild in most patients. Half of the patients where treatment with dupilumab had failed had a good clinical response to tralokinumab. CONCLUSIONS: Tralokinumab was found to be effective in most patients in this cohort with difficult-to-treat, severe AD from daily practice. Interestingly, tralokinumab was also found to be effective in 50% of patients who had previously experienced insufficient response or adverse events with dupilumab treatment

Noninvasive Skin Barrier Assessment: Multiparametric Approach and Pilot Study

The epidermal barrier function is disrupted in various inflammatory skin diseases. Accurate methods to measure skin barrier function are needed to assess the effect of therapeutic agents. Therefore, we developed a noninvasive multiparametric approach to measure four different parameters regarding the skin barrier. In the current pilot study, we evaluate this method in 14 healthy volunteers. We assessed erythema, transepidermal water loss (TEWL), water content, and epidermal thickness at both cheeks before and 30 min after application of Lanette and Vaseline-Lanette cream. For this, we used spectrophotometry, the Aquaflux device, the Epsilon device, and reflection confocal microscopy, respectively. Stratum corneum (SC) thickness was significantly increased after application of both creams (p &lt; 0.05), and this increase was larger after Lanette cream compared to after Vaseline-Lanette cream (p = 0.035). Erythema, TEWL, and water content did not significantly change after cream application. Our multiparametric approach is promising and offers a feasible and practical way to quickly obtain multifaceted information about skin barrier function. Further exploration of this approach after prolonged use of cream and in conditions of disrupted skin barrier are recommended areas for future research

Adjusted dose regimens in dupilumab treatment for atopic dermatitis: Daily practice experiences

Background Clinical trials with dupilumab in atopic dermatitis (AD) patients showed a trend towards better effectiveness with a weekly or biweekly dosing interval, compared with extended dosing intervals. However, literature about adjusted dose regimens in daily practice is lacking. Objectives To evaluate adjusted dosing intervals of dupilumab for AD in daily practice. Methods An observational, longitudinal cohort study was conducted in AD patients who started dupilumab treatment in daily practice. Dosing intervals were adjusted upon shared decision making between physicians and patients in daily practice, without strict criteria. Disease courses of patients with shortened or extended dosing intervals were illustrated using spaghetti plots. In addition, data of patients who were treated with standard or extended dosing intervals were analysed using linear mixed effect (LME) models to determine the estimated effectiveness of extended dosing regimens. Results In total, 180 AD consecutive patients treated with dupilumab in daily practice were included in our study. Patients with an extended dosing interval (n = 28) had relatively low Eczema Area and Severity Index (EASI) scores at the time of interval adjustment (range: 0−7) and the majority of patients showed continuous effectiveness after adjustment. In patients with a shortened dosing interval (n = 26), the scores at the time of adjustment were more widespread (range: 0−34) and follow-up showed variable disease courses. Based on the LME model, we found an overall continuous improvement of EASI scores in time, in patients with a regular and extended interval. Conclusions Patients with extended dosing intervals showed sustained effectiveness, similar to patients with standard dosing intervals. The effects of shortened intervals on disease severity could not be adequately analysed due to methodological limitations in this retrospective study