Orismilast in moderate-to-severe psoriasis: Efficacy and safety from a 16-week, randomized, double-blinded, placebo-controlled, dose-finding, and phase 2b trial (IASOS).

BACKGROUND: Orismilast is a novel oral phosphodiesterase-4 (PDE4) B/D inhibitor being investigated as a potential treatment for moderate-to-severe psoriasis. OBJECTIVE: To evaluate efficacy and safety of orismilast modified-release formulation in moderate-to-severe psoriasis. METHODS: This multicenter, randomized (1:1:1:1 to 20, 30, 40 mg orismilast or placebo, twice daily), double-blinded, placebo-controlled, parallel-group, phase 2b, 16-week, dose-ranging study evaluated orismilast in adults with moderate-to-severe plaque psoriasis (NCT05190419). Efficacy end points were analyzed using multiple imputation. RESULTS: Of 202 randomized patients, baseline characteristics were balanced across arms, except greater severe disease proportions for orismilast vs placebo. Orismilast showed significant improvements in the primary end point, percentage change in Psoriasis Area and Severity Index (PASI), from baseline to week 16 (orismilast -52.6% to -63.7% and placebo, -17.3%; all P <.001). Greater proportions receiving orismilast achieved PASI75 (39.5%-49.0%; P <.05) and PASI90 (22.0%-28.3%; P <.05 for 20 and 40 mg) vs placebo (PASI75, 16.5% and PASI90, 8.3%) at week 16. Safety findings were as expected with PDE4 inhibition; dose-dependent tolerability effects observed. LIMITATIONS: Small sample size, disease severity imbalance between groups, limited duration and diversity in study population. CONCLUSION: Orismilast demonstrated greater efficacy vs placebo and a safety profile in line with PDE4 inhibition.

Implementing well-being in the management of psoriasis: An expert recommendation.

Psoriasis causes detriment in a person's physical, mental and social health which impairs their quality of life (QoL). However, the current psoriasis management may not adequately address all relevant health domains. Since the goal of healthcare is to restore or maintain health, health outcomes should include all areas of the patient's overall health. Life satisfaction, QoL and patient well-being are essential to a comprehensive approach to the disease. With the inclusion of more people-centred policies, care of patients with psoriasis should evolve towards a holistic and integrated assessment of the disease impact, including subjective measures of well-being in order to encompass all aspects of health. The main objective of this expert review is to give the concept of well-being a place as an entity within the holistic therapeutic approach for patients with psoriasis. Identifying and defining common goals beyond the skin with the patient and testing them throughout the course of treatment will benefit and enhance treatment success. We propose a series of recommendations for application in clinical practice, providing tangible clinical guidance for implementing well-being in the management of psoriasis. Among the recommendations are the need to initially listen to the patient, to know their level of empowerment or what they want to achieve, their preferences in decision making, the evaluation of not only the physical but also the emotional impact of the disease (well-being), the definition of the aspects that can generate a cumulative deterioration of the disease throughout life, and a continuous assessment of the patient's preferences with the opinion of the expert clinician and the integration of the knowledge of external clinical evidence.

SARS-CoV-2 infection among psoriasis patients in Germany: Data from the German registries PsoBest and CoronaBest.

BACKGROUND: Limited data exist on the characteristics of SARS-CoV-2 infections in German patients with psoriasis or psoriasis arthritis (PsA). This study analyses COVID-19 prevalence and severity of symptoms in these patients. PATIENTS AND METHODS: Participants of the German registries PsoBest and CoronaBest were surveyed in February 2022. Descriptive analyses were conducted. RESULTS: 4,818 patients were included in the analysis, mean age of 56.4 years. Positive SARS-CoV-2 tests were reported by 737 (15.3%) patients. The most frequently reported acute symptoms were fatigue (67.3%), cough (58.8%), and headache (58.3%). Longer-lasting symptoms after COVID-19 were reported by 231 of 737 patients after the acute phase. For most patients (92.9%), systemic treatment for their psoriasis or PsA was not modified during the pandemic. Patients positively tested for SARS-CoV-2 were younger on average and had more often changes in the therapy of psoriasis than negatively tested patients (8.5% vs. 5.4%). CONCLUSIONS: In this cohort of patients with psoriasis or PsA undergoing systemic treatment, SARS-CoV-2 infections were common but less frequent than in the general German population. No risk signals for more severe COVID-19 or increased infection rates were observed in the patients. In addition, systemic treatments remained largely unchanged, so that no risks can be attributed to these therapies.

Bimekizumab maintenance of response through 3†years in patients with moderate-to-severe plaque psoriasis: results from the BE BRIGHT open-label extension trial.

BACKGROUND: Given the chronic nature of psoriasis and the loss of response that can be observed with therapies over time, it is important to understand the long-term efficacy of new treatments. OBJECTIVES: To evaluate maintenance of Week 16 responses with bimekizumab (BKZ) treatment through Year 3, in patients with moderate-to-severe plaque psoriasis. METHODS: Data were pooled from BKZ-treated patients in the 52-week (BE VIVID) and 56-week (BE READY and BE SURE) phase III studies, and their ongoing open-label extension (OLE), BE BRIGHT. Efficacy outcomes are reported through 3 years of BKZ treatment in patients with an efficacy response at Week 16. Missing data were imputed primarily using modified nonresponder imputation (mNRI), with nonresponder imputation and observed case data also reported. RESULTS: A total of 989 patients were randomized to BKZ at baseline in BE VIVID, BE READY and BE SURE. At Week 16, 693 patients achieved ≥ 90% reduction from baseline in Psoriasis Area and Severity Index (PASI 90), 503 achieved 100% reduction from baseline in PASI (PASI 100), 694 achieved absolute PASI ≤ 2 and 597 achieved body surface area (BSA) ≤ 1%, and continued into the OLE. Of these, 93.0% maintained PASI 90, 80.8% maintained PASI 100, 94.0% maintained PASI ≤ 2 and 90.3% maintained BSA ≤ 1% responses through to 3 years of BKZ treatment (mNRI). Among Week 16 PASI 90 responders, 96.8% and 72.5% also achieved Investigator's Global Assessment 0/1 and PASI 100 at Week 16, respectively, and 92.2% and 73.4% achieved these responses at Year 3 (mNRI). Among Week 16 PASI 100 responders, 76.3% also achieved Dermatology Life Quality Index (DLQI) 0/1 at Week 16, and DLQI 0/1 response increased with continuous BKZ treatment to 89.0% at Year 3 (mNRI). CONCLUSIONS: High levels of clinical response were maintained through to 3 years of BKZ treatment in the vast majority of Week 16 responders. Long-term treatment with BKZ was efficacious, with important benefits for health-related quality of life, in patients with moderate-to-severe plaque psoriasis.

Activation of the aryl hydrocarbon receptor dampens the severity of inflammatory skin conditions.

Environmental stimuli are known to contribute to psoriasis pathogenesis and that of other autoimmune diseases, but the mechanisms are largely unknown. Here we show that the aryl hydrocarbon receptor (AhR), a transcription factor that senses environmental stimuli, modulates pathology in psoriasis. AhR-activating ligands reduced inflammation in the lesional skin of psoriasis patients, whereas AhR antagonists increased inflammation. Similarly, AhR signaling via the endogenous ligand FICZ reduced the inflammatory response in the imiquimod-induced model of skin inflammation and AhR-deficient mice exhibited a substantial exacerbation of the disease, compared to AhR-sufficient controls. Nonhematopoietic cells, in particular keratinocytes, were responsible for this hyperinflammatory response, which involved upregulation of AP-1 family members of transcription factors. Thus, our data suggest a critical role for AhR in the regulation of inflammatory responses and open the possibility for novel therapeutic strategies in chronic inflammatory disorders.

Rapid and sustained improvements in Generalized Pustular Psoriasis Physician Global Assessment scores with spesolimab for treatment of generalized pustular psoriasis flares in the randomized, placebo-controlled Effisayil 1 study.

BACKGROUND: Effisayil 1 was a randomized, placebo-controlled study of spesolimab, which is an anti-IL-36 receptor antibody, in patients presenting with a generalized pustular psoriasis flare. OBJECTIVE: To assess the effects of spesolimab over the 12-week study. METHODS: The primary endpoint of the study was Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) pustulation subscore of 0 at week 1. Patients (N = 53) were randomized (2:1) to receive a single intravenous dose of 900 mg spesolimab or placebo on day 1. Patients could receive open-label spesolimab for persistent flare symptoms on day 8. RESULTS: Most patients receiving spesolimab achieved a GPPGA pustulation subscore of 0 (60.0%) and GPPGA total score of 0 or 1 (60.0%) by week 12. In patients randomized to placebo who received open-label spesolimab on day 8, the proportion with GPPGA pustulation subscore of 0 increased from 5.6% at day 8 to 83.3% at week 2. No factors predictive of spesolimab response were identified in patient demographics or clinical characteristics. LIMITATIONS: The effect of initial randomization was not determined conventionally beyond week 1 due to patients receiving open-label spesolimab. CONCLUSION: Rapid control of generalized pustular psoriasis flare symptoms with spesolimab was sustained over 12 weeks, further supporting its potential use as a therapeutic option for patients.

Efficacy and safety of apremilast in patients with limited skin involvement, plaque psoriasis in special areas and impaired quality of life: Results from the EMBRACE randomized trial.

INTRODUCTION/BACKGROUND: Manifestations of psoriasis in special areas are difficult to treat and are associated with a high disease burden and significant quality of life (QoL) impairment. Topical therapies may be inadequate for these patients, necessitating systemic treatment. OBJECTIVE: The objective of EMBRACE was to evaluate the impact on QoL, efficacy and safety of apremilast 30 mg BID in patients with limited skin involvement with plaque psoriasis manifestations in special areas and impaired QoL. METHODS: EMBRACE (NCT03774875) was a phase 4, randomized, placebo-controlled, multinational study. Patients had plaque psoriasis not controlled by topical therapy; lack of response, contraindication or intolerance to conventional first-line systemic therapy; psoriasis in ≥1 special area (including visible locations, scalp, nails, genital areas or palmoplantar areas); Psoriasis Area and Severity Index (PASI) ≥3 to ≤10; and Dermatology Life Quality Index (DLQI) >10. The primary endpoint was DLQI response (≥4-point reduction) at Week 16. RESULTS: Of 277 randomized patients (apremilast: n = 185; placebo: n = 92), 221 completed Week 16 (apremilast: n = 152; placebo: n = 69). The primary endpoint (≥4-point reduction in DLQI at Week 16) was met by significantly more patients receiving apremilast (73.3%) versus placebo (41.3%; p < 0.0001). Significantly greater improvement in affected body surface area (BSA) and PASI was observed with apremilast versus placebo at Week 16. There were also significantly greater improvements with apremilast versus placebo in itch numeric rating scale (-2.5 vs. -0.9, p < 0.0001) and skin discomfort/pain visual analog scale (-21.5 vs. -5.4, p = 0.0003) and greater achievement of Patient Benefit Index ≥1 (77% vs. 40%, p < 0.0001) at Week 16. No new safety signals were observed. CONCLUSIONS: Apremilast significantly improved skin-related QoL in patients with limited skin involvement with plaque psoriasis in special areas and highly impaired QoL. The safety profile was consistent with prior apremilast studies.

Characterization of patients with psoriatic arthritis in dermatologic and rheumatologic care: analysis of two registries.

BACKGROUND AND OBJECTIVE: Psoriatic arthritis (PsA) is a chronic systemic inflammatory disease affecting the musculoskeletal system, skin and nails. The aim is to characterize sociodemographic and clinical patient profiles documented in dermatologic and rheumatologic care. PATIENTS AND METHODS: Data of 704 patients with PsA from the dermatological Psoriasis Registry PsoBest (PB) and 1066 patients from the rheumatological disease registry RABBIT-SpA (RS) were analyzed. Comparable anamnestic and clinical variables were identified and descriptively analyzed. RESULTS: The mean age was 51.7 years in PB and 51.9 in RS. Disease duration of psoriasis was longer, mean cutaneous severity was higher in PB. However, more patients in RS vs. PB had tender joints and swollen joints. Mean Dermatology Life Quality Index was higher in PB and mean Health Assessment Questionnaire in RS. Patient reported global disease activity and pain were lower in PB. IL-23 inhibitors were used more frequently in PB, and TNF inhibitors in RS. CONCLUSIONS: Clinical specialization was associated with different clinical and treatment patterns of PsA. This may indicate a selection by dominant manifestation of psoriatic disease and potentially by effects of health care access. Psoriatic arthritis should be treated in a multidisciplinary approach considering all facets of this complex disease.

Absolute Psoriasis Area and Severity Index as a valuable marker to determine initial treatment response in psoriasis patients treated with guselkumab in routine clinical care.

Guselkumab is an anti-interleukin-23p19 monoclonal antibody approved as a first-line medication in patients with moderate-to-severe plaque-type psoriasis and second-line in active psoriatic arthritis. In the clinic, patients who have shown a lack of previous treatment efficacy and/or tolerability are often prescribed guselkumab. These patients generally have less severe psoriasis compared to clinical trial cohorts, reflected in lower Psoriasis Area and Severity Index (PASI). To evaluate treatment response in a real-world setting, we conducted a multicenter-retrospective chart review in three specialized dermatological centers. Seventy-four patients who received guselkumab treatment were included in the study and baseline characteristics were described. The mean PASI at baseline was 13.0 (± 6.7). After 12 weeks of treatment 40 patients could be followed up at the participating centers and efficacy was assessed: 72.5% of these patients achieved an absolute PASI ≤5 (55.0% ≤3; 42.5% ≤2) whereas only 57.5% of patients were able to gain a delta PASI reduction of at least 75%. Using the absolute PASI as a treatment goal rather than response rate revealed that guselkumab was highly effective in this real-world setting. In conclusion, the absolute PASI proved to be a more valuable tool to measure treatment outcome.

Application of the Statistical Method to Convert Published PASI 50/75/90/100 into Absolute PASI Response Rate in Patients with Moderate-to-Severe Plaque Psoriasis Treated with Tildrakizumab Based on Data from the Two Pivotal Phase 3 Studies reSURFACE 1 and reSURFACE 2.

BACKGROUND: Absolute Psoriasis Area and Severity Index (PASI) is a key endpoint in psoriasis management. Petto et al. [Pharm Stat. 2019;18(1):4-21] developed a statistical method to estimate the proportion of patients reaching absolute PASI response given baseline PASI score and proportion of patients achieving relative improvements at predefined time points. OBJECTIVES: To test this method on clinical data from two phase 3 tildrakizumab trials (reSURFACE 1/2) comparing estimated absolute PASI ≤1/≤2/≤3/≤5 responses with reference responses from clinical databases. METHODS: Reference PASI responses of ≤1/≤2/≤3/≤5 were extracted from clinical databases. Estimation of absolute PASI ≤1/≤2/≤3/≤5 response rates at week (W) 12 and W28 by treatment and trial were performed. Differences between estimated and reference responses were analysed. Bland-Atman limits of agreement and Passing-Bablok regression to assess variations between estimated and reference responses were performed. RESULTS: Differences between estimated and reference absolute PASI ≤1/≤2/≤3/≤5 responses at W12 and W28 by treatment and trial were of little clinical relevance with an overall mean difference in PASI response proportion of -2.2% (e.g., for the tildrakizumab 100-mg arm, original proportions of patients achieving PASI of ≤1/≤2/≤3/≤5 at W28 were 38.5%/52.2%/63.5%/73.9% and 39.8%/54.8%/63.6%/76.9% [reSURFACE 1 and 2, respectively] vs. estimated proportions of 33.2%/49.8%/62.5%/78.3% and 34.3%/51.6%/64.5%/79.9%). Limits of agreement were -7.1% to 1.4% at W12 and -6.8% to 4.3% at W28. Scatterplots revealed linearity that stood the cusum test in Passing-Bablok regression with slope 1.14 (95% confidence intervals: 1.06 to 1.20). CONCLUSION: Good estimates of absolute PASI response rates were achieved with the application of the statistical method to tildrakizumab data reported in the phase 3 studies, in particular in the verum study arms. Our data support the method provided by Petto et al. [2019] to estimate proportions of psoriasis patients reaching absolute PASI value thresholds using relative PASI improvements.

Effective and Safe Treatment of Psoriatic Disease with the Anti-IL-23p19 Biologic Tildrakizumab: Results of a Real-World Prospective Cohort Study in Nonselected Patients.

BACKGROUND: After registration of drugs, evidence about efficacy and safety is solely based on data of phase 2/3 clinical trial programs. A major drawback is the selection of patients following inclusion/exclusion criteria. There is a considerable time and knowledge gap between study and registry data that evaluate real-world evidence (RWE). To close this gap, prospective cohort data are helpful. OBJECTIVES: Soon after tildrakizumab, an interleukin 23p19-inhibitor, was registered for moderate-to-severe plaque psoriasis, a prospective single-center cohort study was established to evaluate efficacy and safety of tildrakizumab in daily practice. METHODS: Following approval of tildrakizumab, patients with moderate-to-severe plaque psoriasis eligible for systemic treatment were included into the Kiel Tildra Cohort (KTC) and followed using routine assessments of efficacy, psoriasis area and severity index (PASI), body surface area (BSA), dermatology life quality index (DLQI), itch (visual analog scale), and safety. Data of the KTC were compared to the respective phase 3 clinical trials. RESULTS: The KTC included 150 patients differing substantially from those in the trial program. There was a high rate of previous systemic (87.3%) and biologic (31.8%) therapy and of comorbidity in the KTC as compared to the phase 3 studies. Due to the best practice approach, baseline PASI was lower in the KTC, but DLQI was similar in both groups. At the time of this analysis, 126 patients completed week 28, 92 patients week 52, and 58 patients week 76, respectively. There was a constant improvement in PASI, BSA, DLQI, and itch from baseline until week 76. There was no clinically meaningful laboratory abnormality. CONCLUSIONS: Patients treated in routine practice with tildrakizumab differed substantially from the phase 3 studies. Despite systemic pre-treatment and increased comorbidity, tildrakizumab showed comparable efficacy and safety in the KTC. Prospective cohort studies are a suitable tool to generate RWE before registry data become available.

Reaching Treatment Goals in Psoriasis with Conventional Systemic Drugs: How Long Are We Willing to Wait?

OBJECTIVES: The purpose of this study was to investigate the attainment of treatment goals according to the European Consensus Programme (ECP-TGs) from 2011 in patients with moderate to severe psoriasis (Pso) treated with the first conventional systemic therapy and to identify factors that might compromise the attainment of these treatment goals. METHODS: In a multicenter, prospective observational study, patients with moderate to severe Pso, defined as either body surface area (BSA) >10% or psoriasis area severity index (PASI) >10 and dermatology life quality index (DLQI) >10, received a conventional systemic therapy that could be modified at each follow-up visit over the course of 18 months. All subjects signed an informed consent form, were ≥18 years of age as well as systemic therapy naïve, and had regular study visits at months 3, 6, 9, 12, and 18 after baseline. Among others and in addition to demographic and disease-related characteristics at baseline, we documented BSA, PASI, DLQI, and the physician-reported attainment of treatment goals at each follow-up visit. Factors related to a failure in achieving the ECP-TGs (i.e., either Δ PASI ≥75 or Δ PASI ≥50 and <75 with a DLQI ≤5) at month 18 were investigated by multiple logistic regression. Descriptive results are presented as the mean ± SD for interval data, and absolute as well as relative frequencies for nominal data. For this part of the analysis, data at baseline and months 6, 12, and 18 are presented. RESULTS: A total of 133 Pso patients with a mean age and disease duration of 49.5 ± 14.4 and 15.6 ± 12.8 years, respectively, were included in the analysis; 54.1% (n = 72) were male. The mean baseline disease-related outcomes were: BSA: 21.5 ± 15.8%, PASI: 13.7 ± 7.14, and DLQI: 12.0 ± 6.11. The most common conventional systemic therapies initiated at baseline were fumaric acid esters (n = 74, 55.6%), methotrexate (n = 46, 34,6%), and ciclosporin (n = 6, 4.5%). The ECP-TGs were achieved by 58 patients (43.6%) at month 6, 86 patients (64.7%) at month 12, and 97 patients (72.9%) at month 18. An optimized reduced logistic regression model identified the presence of onycholysis/nail dystrophy at two or more digits to be associated with failing to attain the ECP-TGs (OR 10.7, 95% CI 2.5-46.7, p = 0.002). CONCLUSION: Patients with onycholysis/nail dystrophy at two or more digits were identified as having a higher risk of not achieving ECP-TGs under conventional systemic therapy. The ECP-TGs from 2011 were attained by 43.6% of our patients 6 months after starting conventional systemic therapies. In the era of safe, fast, and efficacious Pso therapies, much higher treatment goals might be achieved during therapy. New treatment goals are only of use if patients and dermatologists strive to attain them.

A Structured Intervention for Medical Students Significantly Improves Awareness of Stigmatisation in Visible Chronic Skin Diseases: A Randomised Controlled Trial.

People with visible skin diseases often experience stigmatisation. The aim of this study was to develop and evaluate a new intervention for medical students to counter the stigmatisation of people with skin diseases. The intervention was evaluated using a randomised controlled design. Effectiveness was assessed at 3 time points. Data from 127 participants were analysed. Regarding the outcome "social distance", a significant difference between the measurement points was observed for the intervention group (χ2(2) = 54.32, p < 0.001), which also showed a significant effect on agreement with negative stereotypes (F(1.67, 118.67) = 23.83, p < 0.001, partial η2 = 0.25). Regarding the outcome "agreement with disease-related misconceptions", a significant difference between the measurement time points was observed for the intervention group (χ2(2) = 46.33, p < 0.001); similar results were found for the outcome "stigmatising behaviour" (F(1.86, 131.89) = 6.16, p = 0.003, partial η2 = 0.08). The results should encourage medical faculties to invest in such courses in order to prevent stigmatisation of people with skin diseases.

Time to Loss of Response following Withdrawal of Ixekizumab in Patients with Moderate-to-Severe Psoriasis.

In clinical practice, interruption of treatment may not result in immediate cessation of disease control, and some patients even experience sustained treatment response following treatment interruption. This post hoc analysis of UNCOVER-1 and -2 Phase 3 clinical trials characterized the time to loss of treatment response in patients with psoriasis who responded to ixekizumab through a 12-week treatment period, and who were then re-randomized to placebo for the following 48 weeks. For those with static Physician Global Assessment [sPGA]0/1 and Psoriasis Area and Severity Index [PASI]90 at Week 12, the median time to loss of PASI90 was 16.1 weeks (95% confidence interval 12.7-16.4). For those with PASI100 at Week 12, the median time to loss of PASI100 was 12.1 weeks (95% confidence interval 9.0-13.0). A small subset of patients maintained high levels of disease control through Week 60. This study adds to the growing body of evidence on sustained treatment response following treatment interruption.

Subgroup Analyses by European Country-Specific Reimbursement Requirements Confirm Efficacy for Ixekizumab in Psoriasis.

BACKGROUND: Biologic drugs are generally recommended for treating moderate-to-severe psoriasis. While eligibility criteria are primarily defined by clinical treatment guidelines, access to these therapies varies between European countries and is regulated by country-specific reimbursement criteria. This post-hoc subgroup analysis of integrated data from two phase III trials (UNCOVER-2 and -3) reports the efficacy of ixekizumab relative to that of etanercept in patients with moderate-to-severe plaque psoriasis selected into groups defined by original reimbursement criteria from eight European countries. METHODS: This analysis included baseline and 12-week data from the ixekizumab- and etanercept-treated study populations from UNCOVER-2 and -3. Patients were classified as meeting/not meeting each country-specific biologic eligibility criterion. Efficacy was defined by Psoriasis Area and Severity Index (PASI) 75, 90, and 100 response rates and by Dermatology Life Quality Index (DLQI) (0,1) response rates. Treatment responses across subgroups were analysed using logistic regression models. RESULTS: PASI 75/90/100 response rates were significantly higher for ixekizumab-treated patients than for etanercept-treated patients at week 12 (P<0.05), irrespective of whether predefined reimbursement criteria were met, for all countries, with the exception of PASI 100 response in those meeting reimbursement criteria in Belgium, where sample size was very small. Clinical efficacy outcomes were corroborated by proportions of patients achieving DLQI (0,1) responses. CONCLUSIONS: The overall high efficacy of ixekizumab, and the consistency of the higher treatment effect compared with etanercept, in patients with moderate-to-severe psoriasis across a range of European biologic treatment reimbursement eligibility criteria provides new insights to inform treatment decisions in clinical practice. J Drugs Dermatol. 2022;21(6):659-667. doi:10.36849/JDD.6620.

Generalized pustular psoriasis: overview of the status quo and results of a panel discussion.

Generalized pustular psoriasis (GPP) is a rare, severe, potentially life-threatening, autoinflammatory, neutrophilic skin disease that may be accompanied by fever and leukocytosis. This paper describes the current state of knowledge on GPP in terms of classification, (differential) diagnosis and prevalence. We present a comparison of the genetics and pathoimmunology of GPP and psoriasis vulgaris with the central mechanisms of autoimmunology and autoinflammation. The currently available therapeutic options, expert recommendations for therapy, and data from early clinical trials investigating targeted therapies will be summarized. We present the results of our discussion with 13 experts for psoriasis vulgaris and GPP and give an integrated overview of indication and therapy based on our personal experience and present an outlook on further research questions. Collectively, this article highlights the high unmet need in GPP, as there exists no satisfactory method of diagnosis or treatment to date and new treatment options will be of great therapeutic benefit to those affected.

Sex and Age Influence the Associated Risk of Depression in Patients with Psoriasis: A Retrospective Population Study Based on Diagnosis and Drug-Use.

BACKGROUND: The reported prevalence of depression among individuals with psoriasis varies substantially, and the effect of gender on depression distribution has revealed conflicting results. In addition, using medication to identify cases is uncommon. OBJECTIVE: To study the prevalence of pharmacologically treated depression among individuals with and without psoriasis in a Swedish population using ICD-10 codes and data from the Swedish Prescribed Drug Register. METHODS: A retrospective case-control population-based study was performed including all living individuals (age ≥18 years) in Region Jönköping, southern Sweden (n = 273,536). ICD-10 codes for the diagnosis of psoriasis (L40.*) and depression (F32.* and F33.*), and data on pharmacological treatment from the Swedish Prescribed Drug Register, were extracted from electronic medical records between April 9, 2008 and January 1, 2016. The extraction date was January 1, 2016. RESULTS: The risk of pharmacologically treated depression was increased in individuals with psoriasis (age- and sex-adjusted OR 1.55; CI 1.43-1.68); 21.1% of women with psoriasis received pharmacological treatment for depression during the study period compared to 14.2% in the control population. Prevalence figures for depression were significantly higher in women with psoriasis compared to men. The risk of suffering from depression was highest among male and female patients with psoriasis under the age of 31 years. CONCLUSIONS: Depression is common among patients with psoriasis. The results of the current study underline the need for dermatologists to adopt a holistic approach, looking beyond the skin, when handling patients with psoriasis in every-day clinical practice.

Effectiveness of a structured short intervention against stigmatisation in chronic visible skin diseases: Results of a controlled trial in future educators.

BACKGROUND: Chronic visible skin diseases are highly prevalent, and patients affected frequently report feeling stigmatised. Interventions to reduce stigmatisation are rare. OBJECTIVES: This study aimed to evaluate the effectiveness of a structured short intervention in reducing stigmatising attitudes towards psoriasis in future educators. METHODS: The intervention consisted of four components: (1) self-reflection, (2) education on skin diseases, (3) contact between participants and a person with psoriasis and (4) practising of knowledge via case studies. A quasi-experimental, pre-post study design was chosen with a nonrandomized contemporaneous control group that attended regular lessons. The main outcomes were participants' desire for social distance, stereotype endorsement, illness-related misconceptions and intended behaviour. Intervention effects were analysed using mixed repeated-measures analysis of variance, with Bonferroni post-hoc tests for pairwise comparisons. RESULTS: The sample consisted of 221 students attending vocational training as educators (n = 118 intervention group, n = 103 control group). While no effect of the intervention was found in social distance, small to large effect sizes were observed for intended behaviour (r = .14), illness-related misconceptions (r = .28) and stereotype endorsement (r = .42). The intervention group reported significantly higher satisfaction with the seminar compared to the control group. CONCLUSIONS: Overall, the short intervention was effective at reducing stigmatising attitudes in future educators. In perspective, revised versions could help in reducing stigmatisation in various demographics and promote patient empowerment by acknowledging and including them as experts on their own behalf. PATIENT OR PUBLIC CONTRIBUTION: Patient advocate groups were consulted and involved in the superordinate destigmatization research programme and intervention.

[Recommendations when switching therapy from immunosuppressive drugs to dupilumab in patients with atopic dermatitis]. / Handlungsempfehlung zur Therapieumstellung von Immunsuppressiva auf Dupilumab bei Patienten mit atopischer Dermatitis.

Based on new insights into the molecular pathogenesis of atopic dermatitis, a targeted anti-inflammatory therapy-dupilumab-has recently been approved as treatment alongside glucocorticoids and ciclosporin. Due to their pharmacology, neither glucocorticoids nor ciclosporin nor the off label used substances methotrexate, azathioprine and mycophenolic acid derivatives are suitable for long-term therapy. When switching therapy from small molecular substances to dupilumab, various factors should be considered. Both the specific cause of the change (ineffectiveness, adverse effects or contraindications) as well as the pharmacological conditions should be taken into account. Since there have been no specific clinical studies on this subject so far, the authors relied mainly on a literature search to draw up recommendations for practical everyday use.

Documentation of psoriasis in routine care - expert consensus on a German data set.

BACKGROUND AND OBJECTIVES: Documenting patient data in psoriasis clinical practice can improve care, but standardized and transparent documentation is rare. The current project aimed to develop a data set for the documentation of psoriasis in daily practice. MATERIAL AND METHODS: In four online Delphi rounds and one in-person meeting, 27 psoriasis experts allocated variables to a standard, an optimal and an optional data set. Most of the questions were standardized. Open questions were included to allow for the provision of reasons and to enlarge the data sets. Furthermore, in the in-person meeting we considered a) patients' attitudes and b) dermatologists' information on the current usage and acceptability in Germany. RESULTS: The consensus approach resulted in a data set with 69 variables. The standard data set includes 20, the optimal data set 31 and the optional data set 18 variables. In summary, the data set can mainly be grouped into master data, general status and medical history data, medical history of psoriasis, status of psoriasis, diagnostics and comorbidity, therapies and patient-reported outcomes. CONCLUSIONS: The consensus recommendation of a standard, an optimal and an optional data set for routine care of psoriasis intends to be a decision-making aid and an orientation for both daily practice and further development of documentation systems.