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Summary Background Dupilumab is the first biologic registered for the treatment of moderate‐to‐severe atopic dermatitis (AD), and efficacy was shown in phase III clinical trials (primary outcome at week 16 was reached in 38% of patients). Currently, there are limited daily practice data available for dupilumab, especially when it is combined with systemic immunosuppressants. Objectives To evaluate dupilumab treatment in daily practice in patients with AD. Methods In this observational cohort study, we prospectively included all adult patients with AD who had been treated with dupilumab in two university hospitals in the Netherlands. Concomitant systemic immunosuppressive treatment was monitored. Physician‐reported outcome measures and patient‐reported outcome measures (PROMs) after ≥ 12 weeks of follow‐up were analysed. We used a linear mixed‐effects model to determine changes in scores during follow‐up. Results Ninety‐five patients were included. Of these, 62 patients were using systemic immunosuppressants at baseline; the use of systemic immunosuppressants was continued during dupilumab treatment in 43 patients. From baseline to 16 weeks of treatment, the estimated mean Eczema Area and Severity Index score (0–72) decreased from 18·6 [95% confidence interval (CI) 16·0–21·4)] to 7·3 (95% CI 5·4–10·0), and the estimated mean PROMs showed a decrease of 41–66%. Investigator's Global Assessment 0 or 1 (clear/almost clear) was reached in 38% of the patients. Five patients discontinued dupilumab treatment due to side‐effects or ineffectiveness. Eye symptoms and orofacial (nonocular) herpes simplex virus (HSV) reactivation were reported in 62% and 8% of the patients, respectively. Conclusions Dupilumab treatment in daily practice shows a clinically relevant improvement of physician‐reported outcome measures and PROMs, which is in line with efficacy data from clinical trials. Besides frequently reported eye symptoms and orofacial (nonocular) HSV reactivation, there were no apparent safety concerns. What's already known about this topic? Dupilumab has been shown to be an efficacious treatment for atopic dermatitis in several clinical trials. However, it is known that there may be considerable differences in patient characteristics and treatment responses between clinical trials and daily practice. What does this study add? This study presents the first experience with dupilumab treatment in 95 patients with atopic dermatitis in daily practice in two Dutch university hospitals. Less stringent inclusion and exclusion criteria and follow‐up schedules, in contrast to those used in clinical trials, might better represent daily practice. Dupilumab treatment shows a clinically relevant improvement of physician‐ and patient‐reported outcome measures; besides patient‐reported eye symptoms (in 59 of 95 patients; 62%) and an apparent increase in orofacial (nonocular) herpes simplex virus reactivation (eight of 95 patients; 8%), there were no other safety concerns during follow‐up up to 16 weeks of dupilumab treatment.

Background Healthcare workers (HCWs) are at risk of developing hand dermatitis (HD). Guidelines recommend moisturizers to prevent HD, but in practice their effectiveness has been poorly investigated. Objectives To assess whether an intervention aimed at improving skin care leads to a reduction in HD severity. Methods In this 1‐year randomized controlled trial, 9 wards (285 HCWs) were allocated to an intervention group (IG), and 10 wards (216 HCWs) were allocated to the control group (CG). The intervention included provision of cream dispensers with electronic monitoring of use, regularly communicated to the HCWs. The primary and secondary outcomes were change from baseline in Hand Eczema Severity Index (HECSI) score (ΔHECSI) and change in natural moisturizing factor (NMF) level (ΔNMF). Results At 12 months, the rates of loss to follow‐up were 41% and 39% in the IG and the CG, respectively. The HECSI score was reduced in the IG by −6.2 points (95%CI: −7.7 to −4.7) and in the CG by −4.2 points (95%CI: −6.0 to −2.4). There was no significant difference in ΔHECSI or ΔNMF between the groups. Relative improvement in the HECSI score was significantly higher in the IG than in the CG (56% vs 44%). In a subgroup of HCWs with mild HD, the IG showed a larger HECSI score decrease than the CG ( P < 0.001). Conclusion Although there was no significant effect on the primary outcomes, the intervention showed overall positive effects on the HECSI score.

Background: Evidence on long-term dupilumab treatment for atopic dermatitis in daily practice is lacking.Objective: To investigate patient characteristics, treatment aspects, effectiveness, and safety of up to 84 weeks of dupilumab treatment.Methods: An observational prospective cohort study was conducted of patients with atopic dermatitis starting dupilumab in routine clinical care.Results: Of the 221 included patients, 103 used systemic therapy at baseline. At 84 weeks, we found a change of À15.2 (SE, 1.7) for the Eczema Area and Severity Index, À16.9 (SE, 1.4) for the Patient-Oriented Eczema Measure, and À17.2 (SE, 1.6) for the Dermatology Life Quality Index. We found a trend for improvement over time for the Investigator Global Assessment and Numerical Rating Scale for pruritus. Severe (n = 79) including serious (n = 11) adverse events were observed in 69 patients. Eye complaints were most frequently reported (n = 46). Twenty-one patients adjusted the regular dosing schedule, and 14 patients discontinued treatment, mainly due to ineffectiveness (n = 7).Limitations: Only adverse events of severe and serious nature were registered for feasibility reasons. Conclusion:Daily practice dupilumab treatment of up to 84 weeks is generally well-tolerated, apart from the reporting of eye complaints. It can be considered a long-term effective treatment for atopic dermatitis in combination with topical and initial concomitant systemic treatment, showing a sustained improvement of signs, symptoms, and quality of life.

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Summary Background Comparative, real‐life and long‐term evidence on the effectiveness and safety of phototherapy and systemic therapy in moderate‐to‐severe atopic eczema (AE) is limited. Such data must come from well‐designed prospective patient registries. Standardization of data collection is needed for direct comparisons and data pooling. Objectives To reach a consensus on how and when to measure the previously defined domain items of the TREatment of ATopic eczema (TREAT) Registry Taskforce core dataset for research registries for paediatric and adult patients with AE. Methods Proposals for the measurement instruments were based on recommendations of the Harmonising Outcome Measures for Eczema (HOME) initiative, the existing AE database of TREATgermany, systematic reviews of the literature and expert opinions. The proposals were discussed at three face‐to‐face consensus meetings, one teleconference and via e‐mail. The frequency of follow‐up visits was determined by an expert survey. Results A total of 16 experts from seven countries participated in the ‘how to measure’ consensus process and 12 external experts were consulted. A consensus was reached for all domain items on how they should be measured by assigning measurement instruments. A minimum follow‐up frequency of initially 4 weeks after commencing treatment, then every 3 months while on treatment and every 6 months while off treatment was defined. Conclusions This core dataset for national AE research registries will aid in the comparability and pooling of data across centres and country borders, and enables international collaboration to assess the long‐term effectiveness and safety of phototherapy and systemic therapy used in patients with AE. What's already known about this topic? Comparable, real‐life and long‐term data on the effectiveness and safety of phototherapy and systemic therapy in patients with atopic eczema (AE) are needed. There is a high diversity of outcomes and instruments used in AE research, which require harmonization to enhance comparability and allow data pooling. What does this study add? Our taskforce has reached international consensus on how and when to measure core domain items for national AE research registries. This core dataset is now available for use by researchers worldwide and will aid in the collection of unified data. What are the clinical implications of this work? The data collected through this core dataset will help to gain better insights into the long‐term effectiveness and safety of phototherapy and systemic therapy in AE and will provide important information for clinical practice. Standardization of such data collection at the national level will also allow direct data comparisons and pooling across country borders (e.g. in the analysis of treatment‐related adverse events that require large patient numbers).

Gambichler and colleagues 1 about a decline of programmed death (PD)-1 + circulating T regulatory cells (Tregs) predicting clinical outcome in anti-PD-1 therapy. The study highlights the potential and importance of immune monitoring in anti-PD-1 checkpoint therapy in malignant melanoma. However, their conclusion about anti-PD-1 antibody treatment effecting a decline of PD-1 + Tregs is misleading. A decline of a cell population infers 'disappearance', which normally is not the effect of therapeutic blocking antibodies. Their IgG4 backbones save target cells from antibody and/or complement-dependent cell-mediated cytotoxicity and depletion from circulation. The reported 'decrease' of CD4 + CD25 ++ CD127-PD-1 + T cells thus lacks acknowledging that cell-bound therapeutic anti-PD-1 antibodies may simply interfere with detection by anti-PD1 detection antibodies due to 'steric hindrance'. In fact, it is well established that therapeutic and several clones of detection anti-PD1 antibodies compete for the same epitope. 2,3 Differentiating a 'decrease' from 'not detectable' is important because blocking effects are reversible as soon as trough plasma levels of therapeutic antibodies subside. This implicates possible disease reactivation following treatment discontinuation but also the opportunity to accelerate a washout of the therapeutic antibody if needed. We learned this from natalizumab, an alpha-4 integrin blocking antibody used for the treatment of multiple sclerosis, where discontinuation turned out to be a major problem associated with alpha-4 re-expression dynamics. In contrast, in the case of a rare but fatal treatment complication due to John Cunningham virus reactivation, an accelerated natalizumab washout by plasma exchange allowed a hurrying up of reexpression of alpha-4 for re-establishing immune competence. 4 The question remains as to whether the extent of PD-1 expression is not detectable because of bound therapeutic antibody or because of a true decrease in the form of shedding or internalization of receptor-antibody complexes. Of note, Zelba and colleagues already approached this question and developed a flow cytometry method for quantifying PD-1-expressing T cells including the detection of cell-bound therapeutic antibodies with antihuman IgG4 detection antibodies. 3 Our second point concerns the patient highlighted in Figure 1 in the article by Gambichler et al., 1 showing a paradoxical increase of PD-1 + Treg frequencies under anti-PD-1 therapy. This astonishing observation raises the question of an increased drug-antibody turnover, possibly due to the presence of anti-PD-1 neutralizing antibodies. According to the European Medicines Agency/European Public Assessment Report product information for Opdivo and Keytruda, 5,6 antidrug antibodies occurred in 11% of 2022 nivolumab-treated patients, with neutralizing antidrug antibodies in 0Á7% patients, and in 2% of 2034 pembrolizumab-treated patients with neutralizing antidrug antibodies in 0Á4%. Although rare, anti-PD-1 neutralizing antibodies occur and...

Background Studies have suggested incremental short-term adverse events (AE) after repeated vaccination. In this report, we assessed occurrence and risk factors for short-term AEs following repeated SARS-CoV-2 vaccination in patients with various immune-mediated inflammatory diseases (IMIDs). Methods Self-reported daily questionnaires on AEs during the first 7 days after vaccination were obtained of 2259 individuals (2081 patients and 178 controls) participating in an ongoing prospective multicenter cohort study on SARS-CoV-2 vaccination in patients with various IMIDs in the Netherlands (T2B-COVID). Relative risks were calculated for potential risk factors associated with clinically relevant AE (rAE), defined as AE lasting longer than 2 days or impacting daily life. Results In total, 5454 vaccinations were recorded (1737 first, 1992 second and 1478 third vaccinations). Multiple sclerosis, Crohn’s disease and rheumatoid arthritis were the largest disease groups. rAEs were reported by 57.3% (95% CI 54.8–59.8) of patients after the first vaccination, 61.5% (95% CI 59.2–63.7) after the second vaccination and 58% (95% CI 55.3–60.6) after the third vaccination. At day 7 after the first, second and third vaccination, respectively, 7.6% (95% CI 6.3–9.1), 7.4% (95% CI 6.2–8.7) and 6.8% (95% CI 5.4–8.3) of patients still reported AEs impacting daily life. Hospital admissions and allergic reactions were uncommon (<0.7%). Female sex (aRR 1.43, 95% CI 1.32–1.56), age below 50 (aRR 1.14, 95% CI 1.06–1.23), a preceding SARS-CoV-2 infection (aRR 1.14, 95% CI 1.01–1.29) and having an IMID (aRR 1.16, 95% CI 1.01–1.34) were associated with increased risk of rAEs following a vaccination. Compared to the second vaccination, the first vaccination was associated with a lower risk of rAEs (aRR 0.92, 95% CI 0.84–0.99) while a third vaccination was not associated with increased risk on rAEs (aRR 0.93, 95% CI 0.84–1.02). BNT162b2 vaccines were associated with lower risk on rAEs compared to CX-024414 (aRR 0.86, 95% CI 0.80–0.93). Conclusions A third SARS-CoV-2 vaccination was not associated with increased risk of rAEs in IMID patients compared to the second vaccination. Patients with an IMID have a modestly increased risk of rAEs after vaccination when compared to controls. Most AEs are resolved within 7 days; hospital admissions and allergic reactions were uncommon. Trial registration NL74974.018.20, Trial ID: NL8900. Registered on 9 September 2020.