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Additional file 1. Table 1. The contents and coding algorithms applied to PSO PROMs. Table 2. Baseline characteristics of the 187 PSO PROMs respondents. Table 3. The 120 comments from patients, doctors, and nurses sorted across nine themes. Table 4. The subgroup analyses of patients with a PROM coded as red or yellow/green.

Morten B Haulrig,1 Claus Zachariae,1,2 Lone Skov1,2 1Department of Dermatology and Allergy, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, DK-2900, Denmark; 2Copenhagen Research Group for Inflammatory Skin (CORGIS), Hellerup, DenmarkCorrespondence: Morten B HaulrigDepartment of Dermatology and Allergy, Herlev and Gentofte Hospital, Gentofte Hospitalsvej 15, DK-2900, DenmarkTel +45 38 67 31 32Fax +45 38 67 71 18Email Morten.bahrt.haulrig@regionh.dkAbstract: Psoriasis is a chronic inflammatory skin disease that affects up to 1.2% of children and adolescents. The treatment options for childhood psoriasis are often based on the same principles as in adults. However, most data on safety and efficacy derive from adult studies, and only a few of the frequently used treatments have achieved approval for use in children. The aim of this study was to review the current literature on off-label treatments for psoriasis in children and adolescents. We searched PubMed and identified 50 studies on off-label treatments. Of these, 23 studies were clinical trials (four randomized). There are only a small number of available studies on off-label treatments for children and adolescents with psoriasis, and many of these are retrospective reviews with few participants. Despite the current lack of studies, we still recommend the use of unapproved treatments since we have clinical experience with treatments such as topical corticosteroids, vitamin D analogs, and methotrexate that have shown promising effects. Regular clinical trials are needed to investigate the safety and efficacy of unapproved treatments. Due to The Pediatric Investigation Plans issued by The European Union, new drugs developed by pharmaceutical companies are required to undergo clinical trials in a pediatric population to get their application for marketing authorization processed. This will hopefully lead to much more data on the efficacy and safety of the new treatments, including treatments for children and adolescents with psoriasis.Keywords: psoriasis, unapproved treatment, childhood, adolescents

Patients with moderate-to-severe atopic dermatitis (AD) or psoriasis often require systemic immunomodulatory therapy. The uncertainty of the potential of these therapies to increase the risk of more serious illness due to Coronavirus disease 2019 (COVID-19) may have caused anxiety and led to treatment discontinuation. Therefore, we conducted an anonymous questionnaire on concerns of COVID-19 in patients with AD or psoriasis treated with systemic immunomodulatory therapy.

Charlotte Näslund-Koch,1 Claus Zachariae,1,2 Lone Skov1,2 1Department of Dermatology and Allergy, Herlev and Gentofte Hospital, Copenhagen, Denmark; 2Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkCorrespondence: Claus Zachariae Department of Dermatology and AllergyUniversity of Copenhagen, Herlev and Gentofte Hospital, Gentofte Hospitalsvej 15, Hellerup 2900, DenmarkTel +4538673203Fax +4538677615Email claus.zachariae@regionh.dkAbstract: Psoriasis is a common immune-mediated chronic inflammatory disease, and observations have pointed toward the IL-23/Th17 cell axis as having a key role in the pathogenesis of psoriasis. This new immunological understanding of the pathogenesis has been translated into targeted and highly effective biologic therapies. Tildrakizumab is a humanized IgG1/k monoclonal antibody targeting the p19 unit of IL-23 and has been registered for the treatment of patients with moderate-to-severe chronic plaque psoriasis in adults since 2018. This review provides an overview of the efficacy and safety of tildrakizumab, focusing on the results from clinical trials. In both Phase II and III trials, tildrakizumab 100 and 200 mg was significantly more efficacious than both placebo and etanercept at week 12. The effect of tildrakizumab continued to increase until week 28. Long-term follow-up showed high levels of efficacy for up to 3 years. Despite no difference between 100 and 200 mg in Phase III studies, subgroup analyses showed better efficacy when treated with 200 mg in patients with bodyweight ≥ 90 kg. The overall drug safety was good, and besides discrete higher incidence of nasopharyngitis, the conducted clinical trials show that tildrakizumab was very well tolerated without any safety concerns. Compared to other IL-23p19 inhibitors, tildrakizumab seemed to have slightly lower efficacy. However, to determine its position in the treatment algorithm of psoriasis, head-to-head trials with other IL-17, IL-12/23, and IL-23 inhibitors and long-term real-world data are required.Keywords: tildrakizumab, IL-23p19, biologics, psoriasis, safety, efficacy

This cohort study compares the use of methotrexate vs biologic agents in children with moderate to severe psoriasis. Question What is the association between use of methotrexate vs biologics and psoriasis severity and drug survival (rate and duration of adherence to a specific drug regimen) in pediatric patients with moderate to severe psoriasis? Findings In this cohort study including 234 pediatric patients with moderate to severe psoriasis, those receiving biologics were more likely than those treated with methotrexate to achieve a Physician Global Assessment status of clear/almost clear and 75% or more improvement of the Psoriasis Area and Severity Index rating at 6 months. In addition, biologics were associated with better drug survival rates at 1, 3, and 5 years, with comparable discontinuation rates owing to lack of response. Meaning In pediatric patients with psoriasis, treatment with biologics may be associated with a significantly greater reduction in psoriasis severity than methotrexate; nevertheless, with 35.6% of the patients achieving clear/almost clear and 40.0% reaching 75% or more improvement on the Psoriasis Area and Severity Index, methotrexate remains an effective treatment for pediatric psoriasis. Importance Few studies have compared the use of methotrexate and biologics, the most commonly used systemic medications for treatment of moderate to severe psoriasis in children. Objective To assess the real-world, 6-month reduction in psoriasis severity and long-term drug survival (rate and duration of adherence to a specific drug) of methotrexate vs biologics in plaque psoriasis in children. Design, Setting, and Participants A retrospective medical records review was conducted at 20 European and North American centers. Treatment response was based on site-reported Psoriasis Area and Severity Index (PASI) and/or Physician Global Assessment (PGA) scores at baseline and within the first 6 months of treatment. Participants included all 234 consecutively seen children with moderate to severe psoriasis who received at least 3 months of methotrexate or biologics from December 1, 1990, to September 16, 2014, with sufficient data for analysis. Data analysis was performed from December 14, 2015, to September 1, 2016. Main Outcomes and Measures PASI, with a range from 0 to 72 (highest score indicating severe psoriasis), and/or PGA, with a scale of 0 (clear), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe), and 5 (very severe). Results Of 234 pediatric patients (103 boys [44.0%]; 131 girls [56.0%]) treated with methotrexate and/or biologics, 163 patients (69.7%) exclusively received methotrexate, 47 patients (20.1%) exclusively received biologics, and 24 children (10.2%) received methotrexate and biologics sequentially. Of the latter cohort, 23 children were treated initially with methotrexate. Mean (SD) age at initiation was 11.6 (3.7) years for methotrexate and 13.3 (2.9) years for biologics (73.2% for etanercept) (P = .002). Among patients evaluated by a scoring method at 6-month follow-up, 75% or greater improvement in PASI (PASI75) was achieved in 12 of 30 patients (40.0%) receiving methotrexate and 20 of 28 patients (71.4%) receiving biologics, and PGA was clear/almost clear (PGA 0/1) in 41 of 115 patients (35.6%) receiving methotrexate and 18 of 37 patients (48.6%) receiving biologics. Achieving PASI75 and/or PGA 0/1 between baseline and 6 months was more likely with biologics than methotrexate (PASI75: odds ratio [OR], 4.56; 95% CI, 2.02-10.27; P < .001; and PGA 0/1: OR, 2.00; 95% CI, 0.98-4.00; P = .06). Decreased mean PASI and PGA scores were associated with biologics more than with methotrexate (PASI effect, -3.13; 95% CI, -4.33 to -1.94; P < .001; and PGA effect, -0.31; 95% CI, -0.56 to -0.06; P = .02). After 1, 3, and 5 years of use, overall drug survival rates for methotrexate were 77.5%, 50.3%, and 35.9%, and for biologics, the rates were 83.4%, 64.3%, and 57.1%, respectively. Biologics were associated with a better confounder-corrected drug survival than methotrexate (hazard ratio [HR], 2.23; 95% CI, 1.21-4.10; P = .01). Discontinuation owing to lack of response was comparable (HR, 1.64; 95% CI, 0.80-3.36; P = .18). Conclusions and Relevance Methotrexate and biologics appear to be associated with improvement in pediatric psoriasis, although biologics seem to be associated with greater reduction in psoriasis severity scores and higher drug survival rates than methotrexate in the real-world setting. Additional studies directly comparing these medications should be performed for confirmation.

Psoriasis is a common immune-mediated chronic inflammatory disease, and observations have pointed toward the IL-23/Th17 cell axis as having a key role in the pathogenesis of psoriasis. This new immunological understanding of the pathogenesis has been translated into targeted and highly effective biologic therapies. Tildrakizumab is a humanized IgG1/k monoclonal antibody targeting the p19 unit of IL-23 and has been registered for the treatment of patients with moderate-to-severe chronic plaque psoriasis in adults since 2018. This review provides an overview of the efficacy and safety of tildrakizumab, focusing on the results from clinical trials. In both Phase II and III trials, tildrakizumab 100 and 200 mg was significantly more efficacious than both placebo and etanercept at week 12. The effect of tildrakizumab continued to increase until week 28. Long-term follow-up showed high levels of efficacy for up to 3 years. Despite no difference between 100 and 200 mg in Phase III studies, subgroup analyses showed better efficacy when treated with 200 mg in patients with bodyweight ≥90 kg. The overall drug safety was good, and besides discrete higher incidence of nasopharyngitis, the conducted clinical trials show that tildrakizumab was very well tolerated without any safety concerns. Compared to other IL-23p19 inhibitors, tildrakizumab seemed to have slightly lower efficacy. However, to determine its position in the treatment algorithm of psoriasis, head-to-head trials with other IL-17, IL-12/23, and IL-23 inhibitors and long-term real-world data are required.

Methotrexate (MTX) has been used in the treatment of psoriasis and other dermatological diseases for more than 50 years. However, there is limited evidence regarding its effect, dose and monitoring, and a lack of consensus regarding how the drug should be used in daily practice. Although the use of MTX is governed by guidelines, such as the European S3-Guidelines and the National Institute for Health and Care Excellence (NICE) guideline, it is important to discuss and adjust these guidelines to national standards. An expert meeting was held in Denmark at the end of 2014, in order to reach consensus regarding the use of MTX in dermatological practice in Denmark. Participants included dermatologists, hepatologists, paediatricians, clinical biochemists and a rheumatologist. Topics discussed were: liver disease monitoring, teratogenic effects of MTX, risk of cancer, and use of MTX in children. We report here the conclusions of this expert meeting regarding use of MTX in dermatological practice.

Ann Sophie Lønnberg, Claus Zachariae, Lone SkovDepartment of Dermato-Allergology, Gentofte Hospital, University of Copenhagen, Hellerup, DenmarkAbstract: “Psoriasis” is a chronic immune-mediated inflammatory disorder with epidermal hyperplasia. There is some evidence that the cytokine interleukin-17A (often known as IL-17), which is mainly produced by Th17 cells, has a role in the pathogenesis of psoriasis. “IL-17” is a pro-inflammatory cytokine mainly important in the host's defense against extracellular bacteria and fungi. The three new therapies with biologic drugs – brodalumab, secukinumab, and ixekizumab – all target the IL-17 signaling pathway. Secukinumab and ixekizumab neutralize IL-17A, while brodalumab blocks its receptor. Results from clinical trials have shown marked improvements in disease severity in patients with moderate-to-severe plaque psoriasis, using any of these three drugs. The biologic agents were generally well tolerated, but the duration of the trials was relatively short. In this review, we focus on the role of the IL-17 cytokine family in the pathogenesis of psoriasis; the efficacy, safety, and tolerability of brodalumab, secukinumab, and ixekizumab in clinical trials; and possible differences between targeting of the IL-17A receptor and targeting of the IL-17A ligand.Keywords: anti-IL-17 agents, IL-17, brodalumab, secukinumab, ixekizumab, psoriasis

IL-8 is a chemokine that has been implicated in a number of inflammatory diseases involving neutrophil activation. HuMab 10F8 is a novel fully human mAb against IL-8, which binds a discontinuous epitope on IL-8 overlapping the receptor binding site, and which effectively neutralizes IL-8-dependent human neutrophil activation and migration. We investigated whether interference in the cytokine network by HuMab 10F8 might benefit patients suffering from palmoplantar pustulosis, a chronic inflammatory skin disease. Treatment of patients with HuMab 10F8 was well tolerated and significantly reduced clinical disease activity at all five endpoints, which included a >= 50% reduction in the formation of fresh pustules. IL-8 neutralization was monitored at the site of inflammation by assessing exudates of palmoplantar pustulosis lesions. HuMab 10F8 sequestered IL-8 in situ, as observed by rapid dose-dependent decreases of IL-8 concentrations immediately following Ab infusion. These data demonstrate a critical role for IL-8 in the pathophysiology of palmoplantar pustulosis. HuMab 10F8 is capable of interrupting IL-8 activity in vivo and represents a candidate for treatment of inflammatory diseases and other pathological conditions associated with IL-8 overproduction.