Brodalumab Versus Guselkumab in Patients with Moderate-to-Severe Psoriasis with an Inadequate Response to Ustekinumab: A Randomized, Multicenter, Double-Blind Phase 4 Trial (COBRA).

INTRODUCTION: Despite improved treatment options for plaque psoriasis within the last decades, some patients still have an inadequate response to treatment. Direct clinical evaluation between therapies used after biologic failure could facilitate physicians' choice of treatment. METHODS: COBRA (NCT04533737) was a randomized (1:1), blinded (patient and assessor), 28-week, active-comparator trial conducted in Europe from December 2020 to December 2022. The objective was to compare the efficacy and safety of brodalumab versus guselkumab in adults with moderate-to-severe plaque psoriasis and inadequate response to ustekinumab. Patients received either brodalumab 210 mg or guselkumab 100 mg. The primary [having Psoriasis Area and Severity Index (PASI)-100 response at week 16] and key secondary (time to PASI-100 response) endpoints were tested in a fixed sequence. RESULTS: Due to delays and enrollment challenges, recruitment was terminated with 113 patients enrolled of 240 planned. The proportion of patients having PASI-100 at week 16 for brodalumab was 53.4% compared with 35.9% for guselkumab [odds ratio (OR) 2.05; 95% confidence interval (CI) 0.95, 4.44; p = 0.069]. As this was not statistically significant, the hierarchical testing procedure was stopped. All other secondary PASI endpoints had nominal p-values below 0.05 in favor of brodalumab. In the time to PASI response analyses, brodalumab separated from guselkumab in estimated cumulative incidence of patients achieving a response from week 2 onward, suggesting fast onset of action with brodalumab. Quality of life measures improved in both treatment groups. The safety findings were consistent with the known safety profiles. CONCLUSIONS: Brodalumab showed a tendency toward better and earlier effect than guselkumab in patients who had failed ustekinumab. Thus, this trial provides important information in assisting physicians in their choice of therapy for patients who have failed their prior anti-interleukin (IL)-12/23 treatment. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04533737.

Efficacy and Safety of Topical Tacrolimus Microemulsion Applied Twice Daily in Patients with Mild to Moderate Scalp Psoriasis.

INTRODUCTION: Involvement of the scalp is common in psoriasis and severely affects the quality of life of those affected. It is difficult to treat and places special demands on the galenics of a drug formulation. Tacrolimus is a calcineurin inhibitor and is approved as an ointment formulation for the treatment of atopic dermatitis. The efficacy and safety of topically applied tacrolimus have also been studied and proven for psoriasis. However, no proprietary pharmaceutical product is currently approved for this indication. METHODS: A multicenter, double-blind, vehicle-controlled phase 3 study was conducted to evaluate the efficacy and safety of 0.1% tacrolimus microemulsion when applied topically twice daily in 128 patients independently of sex with scalp psoriasis. RESULTS: The primary efficacy analysis showed a scalp Investigator Global Assessment (s-IGA) of 0 (absence of disease) or 1 (very mild disease) at 8 weeks in 28.6% of subjects in the tacrolimus group, indicating a significantly better response (p = 0.0476, chi-square test) versus 12.7% of subjects in the placebo group (difference of 15.9%-points). The Dermatology Life Quality Index (DLQI) improved over time and was more pronounced in the group treated with tacrolimus-containing microemulsion than in the placebo group, but showed no statistically significant difference after 8 weeks of use (p = 0.193, ANCOVA). The safety analysis revealed no evidence of cutaneous side effects other than those known. Toxicologically relevant serum levels of tacrolimus could be excluded. CONCLUSION: The study data show that 0.1% tacrolimus microemulsion has good efficacy and safety in the treatment of scalp psoriasis.

[Janus kinase inhibitors : Indications, efficacy, uses, what should be taken into account?] / Januskinaseinhibitoren : Indikationen, Wirkung, Einsatz: Was ist zu beachten?

Janus kinase inhibitors (JAKi) represent an immunomodulatory targeted therapy in various dermatoses. Throughout the past few years, JAKi have been approved for atopic dermatitis (AD), psoriasis vulgaris (PSO), alopecia areata (AA), and vitiligo. Further indications are currently under investigation. In this article the various systenic and topical JAKi used in dermatology are being presented regarding their efficacy and safety profile. A specific focus will be set on handling with safety issues including screening and control measures during treatment with JAKi. In addition, future use of JAKi in various dermatological diseases for which nowadays only insufficient therapy options are available is being discussed.

Learning from the Experiences in the COVID-19 Pandemic - Impact on Quality of Life and Challenges for the Staff of a Dermatological Hospital and Rehabilitation Center in Germany: A Retrospective Analysis.

Purpose: During the COVID-19 pandemic, infections could also be detected among the staff and patients of the dermatological hospital Bad Bentheim (Germany). This retrospective analysis aims to better understand the impact of the pandemic on health care workers. The results could help improve future pandemic plans and measures to protect health care workers. Patients and Methods: In 2020, the whole staff (460 participants) of the dermatological hospital Bad Bentheim had been offered the option to be tested with respect to the antibody status on SARS-CoV-2 (IgG, IgM). The data were collected by means of a blood sample and subsequent questionnaires (22 questions for employees with positive SARS-CoV-2 serology) regarding disease severity, symptoms, disease duration, chains of infection, psychological and physical burden. Both groups were divided by positive or negative serology and data analysis was performed using an independent t-test. Results: It was shown that a COVID-19 Infection clinically presented itself as a respiratory tract infection, differed significantly in severity and duration, but also the long-term consequences in employees with proven COVID-19 disease (n=14, 3.7%) from the employees with non-COVID-19 respiratory diseases (33.6% of the seronegative employees). In addition, there was a significant psychological impairment and burden of COVID-19-affected employees. Our study showed unique insights into infection chains, disease courses, disease severity, symptoms and a significant psychological impairment and burden of COVID-19-affected employees among the COVID-19 positive staff. Conclusion: Our study shows deep insights into infection chains, disease courses, disease severity and symptoms among the COVID-19 positive staff and led to change of behavior with the disease itself and among the health care professionals. This knowledge has the potential to positively influence the handling of similar future events.

A Comparative Analysis of the Predictors, Extent and Impacts of Self-stigma in Patients with Psoriasis and Atopic Dermatitis.

The impact of dermatological diseases goes beyond symptoms and often includes psychosocial burden. Self-stigmatization plays a key role in this relationship and was compared in patients with psoriasis and atopic dermatitis to evaluate the validity of cross-disease stigmatization models. In total, 101 patients per indication were included in this cross-sectional study. Besides sociodemographic and clinical data, patient-reported outcome measures relating to self-stigmatization, depression, anxiety, and quality of life were compared across groups. Sociodemographic and clinical factors were tested for their moderating effects between self-stigmatization and quality of life. Group mean comparisons yielded no significant differences in self-stigmatization between patient groups. In both diseases, self-stigmatization significantly predicted depression and anxiety symptoms as well as quality of life. Current symptoms, not having close social relationships, and lower age predicted self-stigma in patients with psoriasis, whereas the involvement of sensitive body areas, the sum of previous treatments, and female sex were predictors in patients with atopic dermatitis. In both groups, symptoms had significantly moderating effects. The results underline the relevance of self-stigmatization in patients with chronic skin diseases. Awareness should be raised, screening implemented, and psychosocial support offered early on. Assessments, conceptual models of self-stigma, and interventions are probably applicable for both diseases.

Comparison of different skin care regimens in patients with moderate to severe atopic dermatitis receiving systemic treatment: A randomized controlled trial.

BACKGROUND: Moderate to severe AD can be successfully managed by systemic treatments. Current guidelines also recommend emollients or emollients 'plus' and eudermic cleansers for all AD patients to improve the skin barrier and provide anti-irritant and anti-pruritic effects. OBJECTIVES: To investigate the efficacy of skin care (in addition to systemic treatment) with an Emollient 'plus' balm designed to improve the skin barrier and skin microbiome plus a corresponding syndet compared to usual commercial emollients and cleansers. METHODS: In a randomized controlled multicenter study, patients with moderate to severe AD (Severity scoring of atopic dermatitis [SCORAD] score ≥ 40) receiving systemic treatment (cyclosporin A, dupilumab or a Janus kinase inhibitor) were randomized 1:1 to apply twice daily for 10 weeks Emollient 'plus' after pre-cleaning with the syndet (Emollient 'plus' group) or to continue with their usual emollient and cleanser (Control group). Assessments included SCORAD, pruritus on a Visual Analog Scale, Dermatology quality of life questionnaire (DLQI), efficacy and tolerance questionnaires. RESULTS: Included were 57 patients with mean age of 38 years (range 19-70 years). The mean amount of emollient used after 10 weeks was 447.3 g (range 29-1099 g) and 613.2 g (range 97-2565 g) for the Emollient 'plus' versus the Control, respectively (p = 0.0277). After 10 weeks, subjects in the Emollient 'plus' had a significantly greater reduction in current pruritus (p = 0.0277) and a greater reduction in some DLQI items compared to the Control group. CONCLUSIONS: In patients with moderate to severe AD receiving systemic treatment, the Emollient 'plus' regimen significantly improved pruritus and quality of life items compared to the control, while using 23% less product over a 10-week period. These results stress the importance of daily use of emollients, especially emollients 'plus' to improve signs, symptoms and quality of life in patients with AD.

Real-world effectiveness and safety of tildrakizumab in long-term treatment of plaque psoriasis: Results from the non-interventional, prospective, multicentre study TILOT.

BACKGROUND: Plaque psoriasis is a chronic inflammatory disorder affecting the skin and impacting quality of life. Tildrakizumab (TIL) is an IL-23 inhibitor licensed for moderate-to-severe plaque psoriasis. Regulatory approval of medicinal products is based on safety and efficacy data from randomized controlled trials (RCTs) which impose stringent selection criteria. Long-term non-interventional studies (NIS) are needed to establish effectiveness and safety in daily practice bridging the gap between RCTs and the real-world setting. OBJECTIVES: This analysis of the NIS TILOT seeks to evaluate effectiveness and safety of TIL in patients with moderate-to-severe plaque psoriasis in a real-world setting. Secondary objectives include the assessment of the Dermatology Life Quality Index (DLQI), treatment satisfaction and course of scalp and nail disease using Physician Global Assessment (PGA). METHODS: Interim analysis at 52 weeks (W) of the ongoing non-interventional, prospective, long-term multicentre study TILOT. RESULTS: The effectiveness analysis included 412 patients. The mean [standard deviation, SD] Psoriasis Area and Severity Index (PASI) score was 16.0 [9.1] at baseline improving by 82.4% (95% confidence interval [CI], 78.9-86.0) to 2.1 [2.9] at W52. The proportion of patients achieving PASI scores of <3 and <5 increased over time peaking at 74.6% (95% CI, 69.3-79.4) and 88.4% (95% CI, 84.3-91.8) at W52. Scalp-PGA and nail-PGA improved by 79.8% (95% CI, 75.6-84.0) and 72.7% (95% CI, 63.9-81.6), respectively. DLQI of 0/1 was achieved by 48.2% (95% CI, 42.3-54.2). Nine out of 10 physicians and patients expressed a high level of treatment satisfaction. No new safety signals were observed. CONCLUSIONS: This prospective cohort study demonstrates a high degree of effectiveness and a reassuring safety profile of TIL in a real-world setting over 52 weeks. Patients with scalp and nail involvement or pruritus showed marked improvements.

Introduction of a Specific Dermatological Rehabilitation Programme for Patients with Chronic Pruritus: A Pilot Study.

Chronic pruritus is a common symptom, associated with several severe medical conditions, great psychological burden, and reduced quality of life. It also poses socio-economic challenges concerning patients' work loss and healthcare costs. In Germany, medical rehabilitation programmes represent an integral part of the medical care of patients with chronic inflammatory skin diseases. However, such programmes play only a rudimentary role in the treatment of other dermatological diseases, such as dermatological oncology, genetic skin diseases, and chronic pruritus. Therefore, a specific antipruritic dermatological rehabilitation programme was developed in cooperation between the Department of Dermatology of the Medical Rehabilitation Center Bad Bentheim and the Center for Chronic Pruritus of the University Hospital of Muenster, Germany. This prospective study compared short-term patient-reported outcomes (n = 121) at the beginning and end of the rehabilitation programme. The majority of subjects had chronic pruritus on primary diseased, inflamed skin. Significant improvements in pruritus intensity (p ≤ 0.001), quality of life (p ≤ 0.001), anxiety symptoms (p ≤ 0.001) and depression (p ≤ 0.001), as well as an overall patient-relevant benefit (Patient Benefit Index 2.6 ± 1.06) and treatment-related patients' satisfaction, were shown. This suggests that implementation of this standardized rehabilitation programme for treatment of patients with chronic pruritus was successful.

How important is subjective well-being for patients? A qualitative interview study of people with psoriasis.

PURPOSE: This qualitative study aimed to investigate the importance of subjective well-being (SWB) as an outcome of psoriasis treatment from patient's perspective. We focused on the affective component of SWB as assessed with the Daily Experience Sampling Questionnaire (DESQ), a validated daily diary. METHODS: Semi-structured qualitative telephone interviews were conducted with in-patients of a dermatological rehabilitation clinic, after participants had completed the DESQ for up to seven days to get familiar with the concept of SWB. Patients were asked to reflect on the importance of SWB as treatment goal and on its relative importance as compared with other treatment outcomes. We also addressed whether SWB could be an indirect measure of benefit in that it reflects other important outcomes. Transcripts were analyzed using content analysis. RESULTS: Eleven patients participated (24-63 years, mean 53 years, 8 male, 3 female). Participants uniformly confirmed that changes in SWB reflected treatment benefit. All but one considered SWB to be a central aspect of treatment benefit-either as the most important treatment goal or as an indirect benefit indicator. In particular, participants described positive associations of SWB with other outcomes, such as symptoms. They reported that both the disease and the medical treatment had an impact on their SWB, which was reflected in the DESQ. CONCLUSION: Our findings suggest that SWB is a relevant indicator of treatment benefit for patients with psoriasis. Therefore, SWB measures, such as the DESQ, could be used to operationalize patient-relevant benefit of psoriasis treatment, complementing outcome measures currently used.

Unmet Educational Needs and Clinical Practice Gaps in the Management of Generalized Pustular Psoriasis: Global Perspectives from the Front Line.

INTRODUCTION: Generalized pustular psoriasis (GPP) is a rare, potentially life-threatening, neutrophilic, autoinflammatory skin disease characterised by recurrent flares of generalised sterile pustules and associated systemic features. Inconsistent diagnostic criteria and a lack of approved therapies pose serious challenges to GPP management. Our objectives were to discuss the challenges encountered in the care of patients with GPP and identify healthcare provider (HCP) educational needs and clinical practice gaps in GPP management. METHODS: On 24 July 2020, 13 dermatologists from 10 countries (Brazil, Canada, China, Egypt, France, Germany, Japan, Malaysia, the UK and the USA) attended a workshop to share experiences in managing patients with GPP. Educational needs and clinical practice gaps grouped according to healthcare system level were discussed and ranked using interactive polling. RESULTS: Lack of experience of GPP among HCPs was identified as an important individual HCP-level clinical practice gap. Limited understanding of the presentation and pathogenesis of GPP among non-specialists means misdiagnosis is common, delaying referral and treatment. In countries where patients may present to general practitioners or emergency department HCPs, GPP is often mistaken for an infection. Among dermatologists who can accurately diagnose GPP, limited knowledge of treatments may necessitate referral to a colleague with more experience in GPP. At the organisational level, important needs identified were educating emergency department HCPs to recognise GPP as an autoinflammatory disease and improving communication, cooperation and definitions of roles within multidisciplinary teams supporting patients with GPP. At the regulatory level, robust clinical trial data, clear and consistent treatment guidelines and approved therapies were identified as high priorities. CONCLUSIONS: The educational imperative most consistently identified across the participating countries is for HCPs to understand that GPP can be life-threatening if appropriate treatment initiation is delayed, and to recognise when to refer patients to a colleague with more experience of GPP management.

[Erythrodermic psoriasis after COVID-19]. / Erythroderme Psoriasis nach COVID-19-Erkrankung.

We present a clinical case of a patient with acutely exacerbated erythrodermic psoriasis vulgaris after symptomatic infection with SARS-CoV­2 (severe acute respiratory syndrome coronavirus 2). Various factors are already known that can lead to an exacerbation of psoriasis, such as drugs or infections with, for example, streptococcus. An association between psoriasis and an infection with SARS-CoV­2 has been described so far in individual case reports, in which, however, drug treatment with for example hydroxychloroquine, a known trigger of psoriasis, often took place. Later cases of exacerbation of psoriasis, partly as pustular psoriasis have been published also without drug induction. However we present for the first time a case of erythrodermic psoriasis triggered by COVID-19 (coronavirus disease 2019) without an obvious drug trigger.

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.

A Randomized, Double-Blind, Placebo-Controlled, Phase 2a Study to Evaluate the Efficacy and Safety of RIST4721 in Subjects with Palmoplantar Pustulosis.

INTRODUCTION: Palmoplantar pustulosis (PPP) is a chronic inflammatory skin condition with neutrophilic infiltration of the epidermis. RIST4721 antagonizes CXC chemokine receptor type 2, which is important in neutrophil recruitment and migration. In this study, the efficacy and safety of RIST4721 versus placebo were assessed in adult subjects with moderate to severe PPP. METHODS: This phase 2a, multicenter, randomized, double-blind, placebo-controlled study investigated RIST4721 versus placebo in subjects with moderate to severe PPP. Key eligibility criteria included: Palmoplantar Pustulosis Area and Severity Index (PPPASI) ≥ 8 and Palmoplantar Pustulosis Physician Global Assessment ≥ 3. Subjects were randomized 1:1 to RIST4721 300 mg or placebo once daily for 28 days. The primary efficacy endpoints were relative change from baseline in fresh and total pustule count at day 28. RESULTS: Fifteen subjects received RIST4721 and 19 subjects received placebo. Treatment with RIST4721 was found to be generally well tolerated. At day 28, the mean ± standard deviation (SD) relative change from baseline in fresh pustule count was 0.86 ± 0.692 and 0.53 ± 0.561 (P = 0.240) and in total pustule count was 0.99 ± 0.667 and 0.96 ± 0.672 (P = 0.804) for RIST4721 and placebo groups, respectively. Subgroup analysis of subjects with progressing disease demonstrated that subjects with a PPPASI-50 at day 28 was significantly higher for subjects treated with RIST4721 (71%) than placebo (15%) (P = 0.022). CONCLUSION: Preliminary data suggest RIST4721 is well tolerated and may be a potential therapy for patients with PPP. TRIAL REGISTRATION: RIST4721-201 was registered in June 2019 at clinicaltrials.gov: NCT03988335.

[Influence of an adjuvant treatment with an emollient containing 10 % urea, ceramides, glycerin und glyceryl glucoside in patients with psoriasis vulgaris]. / Einfluss einer adjuvanten Basistherapie mit 10 % Urea, Ceramiden, Glycerin und Glyceryl Glucoside bei Patienten mit Psoriasis vulgaris.

BACKGROUND: Guidelines generally recommend an adjuvant treatment with emollients for patients suffering from psoriasis. However evidence for this purpose is limited. PATIENTS AND METHODS: We performed a prospective observational study with an emollient containing 10% urea, ceramides, glycerin and glyceryl glucoside in patients suffering from mild to moderate psoriasis. The patients had to be stable for at least 12 weeks on prior antipsoriatic therapy including topical therapy, systemic treatment or phototherapy which was continued during the trial. RESULTS: A 4-week daily application of the emollient resulted in significant improvement regarding quality of life (measured by DLQI, Dermatology Life Quality Index) and clinical outcome (measured by local PASI, Psoriasis Area and Severity Index) among the treated patients. CONCLUSION: The trial results show that a daily adjuvant treatment with emollients can support a basic antipsoriatic therapy both in aspects of clinical efficacy and quality of life in mild to moderate patients suffering from psoriasis.

Content and value of rehabilitation in dermatology.

The therapy of chronic skin diseases is challenging for both the dermatologist and the patient. Current standards of therapy and individual circumstances of the patient have to be considered. Furthermore, chronic skin diseases are often associated with comorbidities that require treatment adapted to the individual. Therefore, optimal education of the patient and a holistic concept of therapy are needed, in many cases in collaboration with various medical disciplines. In this case, rehabilitation provides an opportunity to address important aspects such as comorbidities, psychosocial burden and limitations at work, in addition to treating the underlying disease. This article describes the differences between acute and rehabilitation health care in dermatology, and illustrates the importance of rehabilitation in dermatology, based on examples of chronic inflammatory skin diseases, chronic pruritus and dermato-oncological diseases.