Publications by authors named "Sandra Philipp"

59 Publications

Biologics for atopic diseases: Indication, side effect management, and new developments.

Allergol Select 2021 5;5:1-25. Epub 2021 Jan 5.

Department of Dermatology and Allergy, Charité Universitätsmedizin, Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Comprehensive Allergy Center, Berlin, Germany.

With the advent of biologicals, more and more therapeutics are available that specifically address specific switch points in the pathomechanism of immunologically dominated diseases. Thus, the focus of diagnostics and therapy (precision medicine) is more on the individual disease characteristics of the individual patient. Regarding the different phenotypes of atopic diseases, severe asthma was the first entity for which biologicals were approved, followed by urticaria, and finally atopic dermatitis and chronic rhinosinusitis with nasal polyps. Experience in the treatment of severe bronchial asthma has shown that the intensity of the response to biological therapy depends on the quality of clinical and immunological phenotyping of the patients. This also applies to different diseases of the atopic form, as patients can suffer from several atopic diseases at the same time, each with different characteristics. Biologics are already emerging that may represent a suitable therapy for allergic bronchial asthma, which often occurs together with severe neurodermatitis, and chronic rhinosinusitis with nasal polyps. In practice, however, the question of possible combinations of biologicals for the therapy of complex clinical pictures of individual patients is increasingly arising. In doing so, the side effect profile must be taken into account, including hypersensitivity reactions, whose diagnostic and logistical management must aim at a safe and efficient therapy of the underlying disease. Increased attention must also be paid to biological therapy in pregnancy and planned (predictable) vaccinations as well as existing infections, such as SARS-CoV-2 infection. Before starting a biological therapy, the immune status should be checked with regard to chronic viral and bacterial infections and, if necessary, the vaccination status should be refreshed or missing vaccinations should be made up for before starting therapy. Currently, reliable data on the effect of biologicals on the immunological situation of SARS-CoV-2 infection and COVID-19 are not available. Therefore, research and development of suitable diagnostic methods for detection of immunologically caused side effects as well as detection of potential therapy responders and non-responders is of great importance.
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http://dx.doi.org/10.5414/ALX02197EDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787364PMC
January 2021

A 39-Year-Old Man With Crohn's Disease and a Unclear Rash on His Left Cheek.

Am J Gastroenterol 2020 Oct 12. Epub 2020 Oct 12.

Interdisciplinary Clinic for Chronic Inflammatory Diseases, Campus Benjamin Franklin, Charité-University Medicine Berlin, Berlin, Germany.

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http://dx.doi.org/10.14309/ajg.0000000000000996DOI Listing
October 2020

Myeloperoxidase Modulates Inflammation in Generalized Pustular Psoriasis and Additional Rare Pustular Skin Diseases.

Am J Hum Genet 2020 09 5;107(3):527-538. Epub 2020 Aug 5.

Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen 91054, Germany. Electronic address:

Generalized pustular psoriasis (GPP) is a severe multi-systemic inflammatory disease characterized by neutrophilic pustulosis and triggered by pro-inflammatory IL-36 cytokines in skin. While 19%-41% of affected individuals harbor bi-allelic mutations in IL36RN, the genetic cause is not known in most cases. To identify and characterize new pathways involved in the pathogenesis of GPP, we performed whole-exome sequencing in 31 individuals with GPP and demonstrated effects of mutations in MPO encoding the neutrophilic enzyme myeloperoxidase (MPO). We discovered eight MPO mutations resulting in MPO -deficiency in neutrophils and monocytes. MPO mutations, primarily those resulting in complete MPO deficiency, cumulatively associated with GPP (p = 1.85E-08; OR = 6.47). The number of mutant MPO alleles significantly differed between 82 affected individuals and >4,900 control subjects (p = 1.04E-09); this effect was stronger when including IL36RN mutations (1.48E-13) and correlated with a younger age of onset (p = 0.0018). The activity of four proteases, previously implicated as activating enzymes of IL-36 precursors, correlated with MPO deficiency. Phorbol-myristate-acetate-induced formation of neutrophil extracellular traps (NETs) was reduced in affected cells (p = 0.015), and phagocytosis assays in MPO-deficient mice and human cells revealed altered neutrophil function and impaired clearance of neutrophils by monocytes (efferocytosis) allowing prolonged neutrophil persistence in inflammatory skin. MPO mutations contribute significantly to GPP's pathogenesis. We implicate MPO as an inflammatory modulator in humans that regulates protease activity and NET formation and modifies efferocytosis. Our findings indicate possible implications for the application of MPO inhibitors in cardiovascular diseases. MPO and affected pathways represent attractive targets for inducing resolution of inflammation in neutrophil-mediated skin diseases.
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http://dx.doi.org/10.1016/j.ajhg.2020.07.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7477008PMC
September 2020

Efficacy of Adalimumab for Nail Psoriasis During 24 Months of Continuous Therapy.

Acta Derm Venereol 2020 Jul 28;100(14):adv00214. Epub 2020 Jul 28.

Psoriasis Research and Treatment Center, Charité-Universitätsmedizin Berlin, DE-10117 Berlin, Germany. E-mail:

Psoriatic nail symptoms are frequent in psoriasis, affecting up to 80% of patients. Therapy responses to nail symptoms are often limited. In this multicentre non-interventional prospective study, 267 patients with nail involvement were treated with adalimumab for a period of 24 months. The efficacy of adalimumab for nail psoriasis was evaluated and predictors for better response were identified. For statistical analysis Kolmogorov-Smirnoff, Mann-Whitney U, Wilcoxon, χ2 and two-tailed Spearman's rank correlation tests were applied. After 3 and 6 months, reductions in Nail Psoriasis Severity Index (NAPSI) of 32.8% (p < 0.001) and almost 50% (p < 0.001), respectively, were observed, compared with baseline scores (mean NAPSI score, 34.2 ± 1.3). In 6 months, 60.0% of patients achieved NAPSI50, 36.4% NAPSI75, and 21.7% NAPSI90. Approximately 42% and 60% of patients achieved NAPSI90 after 12 and 24 months, respectively. At month 12, reduction in NAPSI significantly correlated with improvement in Dermatological Life Quality Index. Stratification by age, sex, and body mass index indicated that treatment was more effective in younger patients and those with higher body mass index. Adalimumab is an effective long-term therapy for nail psoriasis. The amelioration of nail symptoms correlates with an improvements in the skin disease and quality of life.
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http://dx.doi.org/10.2340/00015555-3545DOI Listing
July 2020

Efficacy and Safety of Continuous Risankizumab Therapy vs Treatment Withdrawal in Patients With Moderate to Severe Plaque Psoriasis: A Phase 3 Randomized Clinical Trial.

JAMA Dermatol 2020 06;156(6):649-658

Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.

Importance: Risankizumab selectively inhibits interleukin 23, a cytokine that contributes to psoriatic inflammation.

Objective: To evaluate the efficacy and safety of risankizumab vs placebo and continuous treatment vs withdrawal in adults with moderate to severe plaque psoriasis.

Design, Setting, And Participants: Multinational, phase 3, randomized, double-blind, placebo-controlled trial conducted from March 6, 2016, to July 26, 2018. A total of 507 eligible patients had stable moderate to severe chronic plaque psoriasis for 6 months or longer, body surface area involvement greater than or equal to 10%, Psoriasis Area and Severity Index (PASI) greater than or equal to 12, and a static Physician's Global Assessment (sPGA) score greater than or equal to 3. Intention-to-treat analysis was conducted.

Interventions: Patients were randomized (4:1, interactive response technology) to risankizumab, 150 mg, subcutaneously, or placebo at weeks 0 and 4 (part A1). All patients received risankizumab at week 16. At week 28, patients randomized to risankizumab who achieved an sPGA score of 0/1 were rerandomized 1:2 to risankizumab or placebo every 12 weeks (part B).

Main Outcomes And Measures: Co-primary end points for the part A1 phase included proportions of patients achieving greater than or equal to 90% improvement in PASI (PASI 90) and sPGA score of 0/1 at week 16. The PASI measures severity of erythema, infiltration, and desquamation weighted by area of skin involvement over the head, trunk, upper extremities, and lower extremities; scores range from 0 (no disease) to 72 (maximal disease activity). The sPGA assesses average thickness, erythema, and scaling of all psoriatic lesions; scores range from 0 (clear) to 4 (severe), with 0/1 indicating clear or almost clear. Primary and secondary end points in part B included proportion of rerandomized patients achieving an sPGA score of 0/1 at week 52 (primary) and week 104 (secondary).

Results: Of 563 patients screened, 507 were randomized to risankizumab (n = 407) or placebo (n = 100). Most patients were men (356 [70.2%]); median age was 51 years (interquartile range, 38-60 years). At week 16, 298 patients (73.2%) in the treatment group vs 2 patients (2.0%) receiving placebo achieved a PASI 90 response, and 340 patients (83.5%) receiving risankizumab vs 7 patients (7.0%) receiving placebo achieved sPGA 0/1 scores (placebo-adjusted differences: PASI 90: 70.8%; 95% CI, 65.7%-76.0%; sPGA 0/1: 76.5%; 95% CI, 70.4%-82.5%; P < .001 for both). At week 28, 336 responders were rerandomized to risankizumab (n = 111) or treatment withdrawal (n = 225). At week 52, the sPGA 0/1 score was achieved by 97 patients (87.4%) receiving risankizumab vs 138 patients (61.3%) receiving placebo. At week 104, the sPGA 0/1 score was achieved by 90 patients (81.1%) receiving risankizumab vs 16 patients (7.1%) receiving placebo (placebo-adjusted differences: week 52: 25.9%; 95% CI, 17.3%-34.6%; week 104: 73.9%; 95% CI, 66.0%-81.9%; P < .001 for both). Rates of treatment-emergent adverse events were similar between risankizumab (186 [45.7%]) and placebo (49 [49.0%]) in part A1 and remained stable over time.

Conclusions And Relevance: Risankizumab showed superior efficacy compared with placebo through 16 weeks and treatment withdrawal through 2 years. Risankizumab was well tolerated, with no unexpected safety findings during the 2-year trial.

Trial Registration: ClinicalTrials.gov Identifier: NCT02672852.
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http://dx.doi.org/10.1001/jamadermatol.2020.0723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7142813PMC
June 2020

Fluorescence optical imaging for the detection of potential psoriatic arthritis in comparison to musculoskeletal ultrasound.

J Dtsch Dermatol Ges 2019 Sep;17(9):913-921

Department of Dermatology and Allergy, Charité - Universitätsmedizin Berlin, Berlin, Germany.

Objective: Comparison of fluorescence optical imaging (FOI) with grayscale (GS) and power Doppler ultrasound (PDUS) to detect joint inflammation in patients with confirmed or suspected psoriatic arthritis (PsA).

Methods: Patients (n = 60) with psoriasis and tenderness and/or swelling of joints were separated into two groups: diagnosis confirmed by the treating dermatologist before the start of the study (n = 26), and suspected PsA (n = 34). GS/PDUS of the hand most clinically affected was performed with a dorsal/palmar view (wrist, MCP, PIP, DIP2-5). FOI examination was carried out in a standardized manner by analyzing the predefined Phases 1-3.

Results: FOI was found to be more sensitive than ultrasound (US) for detection of inflammation in PIP/DIP joints (p = 0.035). Confirmed PsA patients showed more findings in FOI P2 and P3, while suspected PsA patients showed more findings in P1. In the confirmed PsA group, most involved joints were MCP joints, while in the suspected PsA group, more involved wrist joints and DIP joints (p = 0.006) were detected with FOI.

Conclusions: The differences between the confirmed and suspected groups indicate that FOI is helpful in the detection of early PsA since P1 may correspond to acute inflammation, whereas P2 and P3 enhancement reflect chronic inflammation. Fluorescence optical imaging might therefore be a novel diagnostic tool for early PsA diagnosis.
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http://dx.doi.org/10.1111/ddg.13931DOI Listing
September 2019

S2k guidelines for the treatment of psoriasis in children and adolescents - Short version part 2.

J Dtsch Dermatol Ges 2019 Sep;17(9):959-973

Department of Dermatology, Erlangen University Medical Center, Erlangen, Germany.

The present guidelines are aimed at residents and board-certified physicians in the fields of dermatology, pediatrics, pediatric dermatology and pediatric rheumatology as well as policymakers and insurance funds. They were developed by dermatologists and pediatric dermatologists in collaboration with pediatric rheumatologists using a formal consensus process (S2k). The guidelines highlight topics such as disease severity, quality of life, treatment goals as well as problems associated with off-label drug therapy in children. Trigger factors and diagnostic aspects are discussed. The primary focus is on the various topical, systemic and UV-based treatment options available and includes recommendations for use and treatment algorithms. Other aspects addressed herein include vaccinations in children and adolescents with psoriasis as well as various disease subtypes such as guttate psoriasis, diaper psoriasis, pustular psoriasis and psoriatic arthritis. Finally, we also provide recommendations for imaging studies and the diagnostic workup to rule out tuberculosis prior to initiating systemic treatment. Note: This article constitutes part 2 of the Sk2 guidelines for the treatment of psoriasis in children and adolescents. Part 1 was published in last month's issue. It contained introductory remarks and addressed aspects of diagnosis and topical treatment.
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http://dx.doi.org/10.1111/ddg.13936DOI Listing
September 2019

S2k guidelines for the treatment of psoriasis in children and adolescents - Short version part 1.

J Dtsch Dermatol Ges 2019 Aug;17(8):856-870

Department of Dermatology, Erlangen University Medical Center, Erlangen, Germany.

The present guidelines are aimed at residents and board-certified physicians in the fields of dermatology, pediatrics, pediatric dermatology and pediatric rheumatology as well as policymakers and insurance funds. They were developed by dermatologists and pediatric dermatologists in collaboration with pediatric rheumatologists using a formal consensus process (S2k). The guidelines highlight topics such as disease severity, quality of life, treatment goals as well as problems associated with off-label drug therapy in children. Trigger factors and diagnostic aspects are discussed. The primary focus is on the various topical, systemic and UV-based treatment options available and includes recommendations for use and treatment algorithms. Other aspects addressed herein include vaccinations in children and adolescents with psoriasis as well as various disease subtypes such as guttate psoriasis, diaper psoriasis, pustular psoriasis and psoriatic arthritis. Finally, we also provide recommendations for imaging studies and the diagnostic workup to rule out tuberculosis prior to initiating systemic treatment. Note: This article constitutes part 1 of the Sk2 guidelines for the treatment of psoriasis in children and adolescents. Part 2 will be published in the next issue. It contains chapters on UV therapy, systemic treatment, tonsillectomy and antibiotics, vaccinations, guttate psoriasis, psoriatic arthritis, complementary medicine, as well as imaging studies and diagnostic workup to rule out tuberculosis prior to systemic treatment.
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http://dx.doi.org/10.1111/ddg.13907DOI Listing
August 2019

Drug survival and reasons for drug discontinuation in palmoplantar pustulosis: a retrospective multicenter study.

J Dtsch Dermatol Ges 2019 May 17;17(5):503-516. Epub 2019 Apr 17.

Department of Dermatology, Georg-August-University Göttingen, Göttingen, Germany.

Background: Palmoplantar pustulosis (PPP) is a chronic inflammatory skin disease-related to psoriasis. Its treatment is challenging, and little is known about the sustainability of different medications. The aim of this study was to analyze drug survival rates and drug discontinuation in the treatment of PPP under real-world conditions.

Patients And Methods: Patients with PPP treated in the dermatology departments of five German university medical centers between 01/2005 and 08/2017 were included in our retrospective study. Drug survival of systemic therapies was assessed with Kaplan-Meier analysis and multivariate regression.

Results: Overall, 347 patients with 935 treatment courses were identified. Within the group of non-biologic systemic agents, apremilast showed the highest median drug survival (15 months), followed by cyclosporine (12 months), the combination of acitretin and topical PUVA (9 months), MTX (8 months), acitretin monotherapy (6 months), alitretinoin (5 months), and fumaric acid esters (3 months). Among biologicals, the highest maintenance rate was detected for certolizumab pegol (restricted mean: 47.4 months), followed by infliximab (median: 26 months), golimumab (22 months), ustekinumab (21 months), adalimumab (18 months), secukinumab (9 months), and etanercept (8 months).

Conclusions: Biologicals and apremilast may serve as second-line options for treatment of PPP and should be further evaluated.
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http://dx.doi.org/10.1111/ddg.13834DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6850581PMC
May 2019

Non-pharmacological Effects in Switching Medication: The Nocebo Effect in Switching from Originator to Biosimilar Agent.

BioDrugs 2018 Oct;32(5):397-404

Hospital Pharmacy, Erasmus University Medical Center, Rotterdam, The Netherlands.

The nocebo effect is defined as the incitement or the worsening of symptoms induced by any negative attitude from non-pharmacological therapeutic intervention, sham, or active therapies. When a patient anticipates a negative effect associated with an intervention, medication or change in medication, they may then experience either an increase in this effect or experience it de novo. Although less is known about the nocebo effect compared with the placebo effect, widespread interest in the nocebo effect observed with statin therapy and a literature review highlighting the nocebo effect across at least ten different disease areas strongly suggests this is a common phenomenon. This effect has also recently been shown to play a role when introducing a medication or changing an established medication, for example, when switching patients from a reference biologic to a biosimilar. Given the important role biosimilars play in providing cost-effective alternatives to reference biologics, increasing physician treatment options and patient access to effective biologic treatment, it is important that we understand this phenomenon and aim to reduce this effect when possible. In this paper, we propose three key strategies to help mitigate the nocebo effect in clinical practice when switching patients from reference biologic to biosimilar: positive framing, increasing patient and healthcare professionals' understanding of biosimilars and utilising a managed switching programme.
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http://dx.doi.org/10.1007/s40259-018-0306-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6182448PMC
October 2018

Application of Photoacoustic Methods and Confocal Microscopy for Monitoring of Therapeutic Response in Plaque Psoriasis.

Skin Pharmacol Physiol 2018 5;31(6):308-315. Epub 2018 Sep 5.

Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Dermatology, Venerology and Allergology, Berlin, Germany.

Psoriasis is prone to relapses and requires long-term therapy that may induce a range of adverse effects; therefore, an efficient and early detection of relapses is desirable. In this study, photoacoustic imaging and confocal laser scanning microscopic (CLSM) methods were investigated for their suitability in psoriasis follow-up examinations. Using a high-resolution photoacoustic system, the vascular structures of 11 psoriatic patients and 6 healthy volunteers were investigated. No differences were detected with respect to the average vessel diameter and vasculature per unit volume in the tissue of healthy volunteers and non-lesional and lesional skin areas of psoriatic patients. By means of CLSM, the diameters of the dermal papillae of 6 volunteers and 6 psoriatic patients were determined. The diameters of the dermal papillae of the healthy volunteers (0.074 ± 0.006 mm) revealed no significant difference when compared to non-lesional skin areas of psoriatic patients (0.079 ± 0.005 mm). The results obtained for the lesions in psoriatic patients showed a significant difference (Wilcoxon test, p = 0.028) between the diameters of the dermal papillae of the lesional skin areas (0.114 ± 0.012 mm) and the non-lesional skin areas (0.079 ± 0.005 mm). Thus, CLSM can be applied for monitoring psoriasis follow-up examinations.
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http://dx.doi.org/10.1159/000492474DOI Listing
November 2018

S3 Guideline for the treatment of psoriasis vulgaris, update - Short version part 2 - Special patient populations and treatment situations.

J Dtsch Dermatol Ges 2018 Jun;16(6):806-813

Klinik für Dermatologie, Venerologie und Allergologie, Universitätsklinikum Frankfurt, Frankfurt/Main und Arbeitsgruppe EbM Frankfurt, Institut für Allgemeinmedizin, Goethe-Universität Frankfurt, Frankfurt/Main [Department of Dermatology, Venereology and Allergology, Frankfurt University Hospital, Frankfurt/Main and EbM Frankfurt working group, Institute for General Medicine, Goethe University Frankfurt, Frankfurt/Main].

The German guideline for the treatment of psoriasis vulgaris was updated using GRADE methodology. The guideline is based on a systematic literature review completed on December 1, 2016, and on a formal consensus and approval process. The second part of this short version of the guideline covers the following special patient populations and treatment situations: tuberculosis screening before and during psoriasis treatment, choice of psoriasis treatment for individuals wishing to have children, as well as during pregnancy and breast-feeding, and patients with joint involvement and vaccinations. In addition, recommendations on the choice of treatment are presented for patients with the following comorbidities: hepatitis and other hepatic impairment, HIV, malignancies, neurological and psychiatric disorders, ischemic heart disease and congestive heart failure, diabetes mellitus, renal impairment and inflammatory bowel disease.
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http://dx.doi.org/10.1111/ddg.13538DOI Listing
June 2018

S3-Leitlinie zur Therapie der Psoriasis vulgaris Update - Kurzfassung Teil 2 - Besondere Patientengruppen und spezielle Behandlungssituationen.

J Dtsch Dermatol Ges 2018 Jun;16(6):806-814

Klinik für Dermatologie, Venerologie und Allergologie, Universitätsklinikum Frankfurt, Frankfurt/Main und Arbeitsgruppe EbM Frankfurt, Institut für Allgemeinmedizin, Goethe-Universität Frankfurt, Frankfurt/Main.

Die deutsche Psoriasis-Leitlinie zur Behandlung der Psoriasis vulgaris wurde unter Verwendung der GRADE-Methodik aktualisiert. Die Leitlinie wurde aufbauend auf einer systematischen Literaturrecherche (letzte Update-Recherche am 01.12.2016) entwickelt und in einem formalen Konsensus- und Freigabeverfahren verabschiedet. Der zweite Teil dieser Kurzfassung stellt die Empfehlungen zum Tuberkulose-Screening vor und unter Therapie, zur Therapieauswahl bei Kinderwunsch, Schwangerschaft und Stillzeit, vorliegender Gelenkbeteiligung sowie zum Umgang mit Impfungen dar. Zudem werden die Empfehlungen zur Therapieauswahl bei Komorbidität mit Hepatitis und Leberfunktionseinschränkungen, HIV, Tumorerkrankungen, Erkrankungen aus dem neurologischen und psychiatrischen Formenkreis, koronarer Herzkrankheit und Herzinsuffizienz, Diabetes mellitus, Niereninsuffizienz sowie chronisch entzündlicher Darmerkrankung dargestellt.
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http://dx.doi.org/10.1111/ddg.13538_gDOI Listing
June 2018

Maintenance of skin clearance with ixekizumab treatment of psoriasis: Three-year results from the UNCOVER-3 study.

J Am Acad Dermatol 2018 Nov 25;79(5):824-830.e2. Epub 2018 May 25.

Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.

Background: Psoriasis is a chronic disease that may require long-term treatment. Ixekizumab (IXE), which is a high-affinity monoclonal antibody that selectively targets interleukin 17A, is an approved therapy for patients with moderate-to-severe plaque psoriasis.

Objective: To evaluate the efficacy and safety of IXE through 156 weeks from the UNCOVER-3 study in patients who were treated with the recommended dose regimen (160 mg of IXE at week 0, 80 mg every 2 weeks up to week 12, and 80 mg every 4 weeks thereafter).

Methods: Patients randomized to IXE every 2 weeks, IXE every 4 weeks, etanercept twice weekly, or placebo were switched to IXE every 4 weeks during the long-term extension period. Efficacy data were summarized by using the as-observed, multiple imputation, and modified nonresponder imputation methods.

Results: At week 156, 80.5% of patients had achieved at least a 75% improvement from baseline in their Psoriasis Area Severity Index (PASI) score, 66.0% had achived at least a 90% improvement from baseline in their PASI score, and 45.1% had achieved a 100% improvement from baseline in their PASI score with use of the modified nonresponder imputation method, and 97.2% and 86.2% of patients had achived at least a 75% improvement from baseline in their PASI score with use of the as-observed and multiple imputation methods, respectively. Similar response rates were observed in patients with baseline scalp, nail, or palmoplantar involvement. No new safety signals were identified through year 3.

Limitations: No placebo or active comparison after week 12.

Conclusion: IXE sustained high responses with clearance of skin and nail lesions, with no new safety concerns through 3 years.
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http://dx.doi.org/10.1016/j.jaad.2018.05.032DOI Listing
November 2018

S3-Leitlinie zur Therapie der Psoriasis vulgaris Update - Kurzfassung Teil 1 - Systemische Therapie.

J Dtsch Dermatol Ges 2018 May;16(5):645-670

Klinik für Dermatologie, Venerologie und Allergologie, Universitätsklinikum Frankfurt, Frankfurt/Main und Arbeitsgruppe EbM Frankfurt, Institut für Allgemeinmedizin, Goethe-Universität Frankfurt, Frankfurt/Main.

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http://dx.doi.org/10.1111/ddg.13516_gDOI Listing
May 2018

S3 Guideline for the treatment of psoriasis vulgaris, update - Short version part 1 - Systemic treatment.

J Dtsch Dermatol Ges 2018 May;16(5):645-669

Klinik für Dermatologie, Venerologie und Allergologie, Universitätsklinikum Frankfurt, Frankfurt/Main und Arbeitsgruppe EbM Frankfurt, Institut für Allgemeinmedizin, Goethe-Universität Frankfurt, Frankfurt/Main [Department of Dermatology, Venereology and Allergology, Frankfurt University Hospital, Frankfurt/Main and EbM Frankfurt working group, Institute for General Medicine, Goethe University Frankfurt, Frankfurt/Main].

The German guideline for the treatment of psoriasis vulgaris was updated using GRADE methodology. The guideline is based on a systematic literature review completed on December 1, 2016, and on a formal consensus and approval process. The first section of this short version of the guideline covers systemic treatment options considered relevant by the expert panel and approved in Germany at the time of the consensus conference (acitretin, adalimumab, apremilast, cyclosporine, etanercept, fumaric acid esters, infliximab, methotrexate, secukinumab and ustekinumab). Detailed information is provided on the management and monitoring of the included treatment options.
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http://dx.doi.org/10.1111/ddg.13516DOI Listing
May 2018

Scabies outbreak among healthcare workers in a German acute care hospital.

J Infect Prev 2017 Jul 1;18(4):189-192. Epub 2017 Feb 1.

Department of Dermatology, Venerology and Allergology, Chariteplatz 1, Berlin, Germany.

Background: This article reports on a scabies outbreak among healthcare workers (HCW) in an acute care hospital. The outbreak was associated with a patient suffering from a chronic skin disease that was later diagnosed as crusted scabies.

Objective: The objective was to determine the outbreak drivers and define a prevention strategy against future outbreaks.

Methods: All staff that had contact with the patient were treated with 5% permethrin ointment. An interdisciplinary outbreak investigation team was established. The team conducted a questionnaire-based case-control study.

Findings: After the permethrin treatment, no further case was found. Twenty-seven HCWs who had contact with the index patient answered the questionnaire (response rate 73%). The outbreak questionnaire revealed 13 cases of secondary scabies among HCWs. In the multivariable analysis, a lack of glove use (odds ratio [OR], 9.8; value = 0.036) and frequent close physical contact (OR, 8.151; value = 0.038) were associated with increased risk of scabies acquisition.

Discussion: The scabies outbreak was most likely driven by three factors: an index patient with crusted scabies; a delayed diagnosis of this patient; and close physical contact without gloves during his hospital stay. The use of disposable gloves for patients with unclear dermatological diagnosis have the potential to limit future scabies outbreaks.
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http://dx.doi.org/10.1177/1757177417690920DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5496690PMC
July 2017

Safety of Systemic Agents for the Treatment of Pediatric Psoriasis.

JAMA Dermatol 2017 11;153(11):1147-1157

Department of Dermatology, Northwestern University, Chicago, Illinois.

Importance: Use of systemic therapies for moderate to severe psoriasis in children is increasing, but comparative data on their use and toxicities are limited.

Objective: To assess patterns of use and relative risks of systemic agents for moderate to severe psoriasis in children.

Design, Setting, And Participants: A retrospective review was conducted at 20 centers in North America and Europe, and included all consecutive children with moderate to severe psoriasis who used systemic medications or phototherapy for at least 3 months from December 1, 1990, to September 16, 2014.

Main Outcomes And Measures: The minimal core data set included age, sex, severity of psoriasis, systemic interventions, monitoring, adverse events (AEs), and reason for discontinuation.

Results: For 390 children (203 girls and 187 boys; mean [SD] age at diagnosis, 8.4 [3.7] years) with psoriasis who used 1 or more systemic medications, the mean interval between diagnosis and starting systemic therapy was 3.0 years. Methotrexate was used by 270 patients (69.2%), biologic agents (primarily etanercept) by 106 (27.2%), acitretin by 57 (14.6%), cyclosporine by 30 (7.7%), fumaric acid esters by 19 (4.9%), and more than 1 medication was used by 73 (18.7%). Of 270 children taking methotrexate, 130 (48.1%) reported 1 or more AEs associated with methotrexate, primarily gastrointestinal (67 [24.8%]). Folic acid 6 days per week (odds ratio, 0.16; 95% CI, 0.06-0.41; P < .001) or 7 days per week (OR, 0.21; 95% CI, 0.08-0.58; P = .003) protected against gastrointestinal AEs more than once-weekly folic acid, regardless of the total weekly dosage. Methotrexate-associated hepatic transaminase elevations were associated with obesity (35 of 270 patients [13.0%]), but a folic acid regimen was not. Injection site reactions occurred in 20 of 106 patients (18.9%) treated with tumor necrosis factor inhibitors, but did not lead to discontinuation of treatment. Having 1 or more AEs related to medication, gastrointestinal AE, laboratory abnormality, or AE leading to discontinuation of the drug was more likely with methotrexate than tumor necrosis factor inhibitors, but having 1 or more infections related to medication (predominantly upper airway) was less likely. Six patients developed a serious treatment-related AE (methotrexate, 3; fumaric acid esters, 2; and adalimumab, 1), but methotrexate and biologic agents were taken for a mean duration that was 2-fold greater than the mean duration for cyclosporine or fumaric acid esters. No patient developed tuberculosis or a malignant neoplasm.

Conclusions And Relevance: Medication-related AEs occur less often with tumor necrosis factor inhibitors than with methotrexate. Folic acid administration 6 or 7 times per week protected more against methotrexate-induced gastrointestinal AEs than did weekly administration. A prospective registry is needed to track the long-term risks of systemic agents for pediatric psoriasis.
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http://dx.doi.org/10.1001/jamadermatol.2017.3029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5710436PMC
November 2017

Palmoplantar pustulosis - a cross-sectional analysis in Germany.

Dermatol Online J 2017 Apr 15;23(4). Epub 2017 Apr 15.

Department of Dermatology and Allergology, University Bonn, Germany.

Background: Palmoplantar pustulosis (PPP) is a recalcitrant chronic inflammatory skin disease. Data relevant for the medical care of patients with PPP are scarce. Thus, the aim of this work was to investigate the disease burden, clinical characteristics, and comorbidity of PPP patients in Germany.

Patients And Methods: PPP patients were examined in a crosssectional study at seven specialized psoriasis centers in Germany.

Results: Of the 172 included patients with PPP, 79.1% were female and 69.8% were smokers.In addition, 25.0% suffered from psoriasis vulgaris, 28.2% had documented psoriatic arthritis, and 30.2% had a family history of psoriasis. In 77 patients the mean Dermatology Life Quality Index (DLQI) was 12.2 ± 7.7 (mean ± SD). The mean Psoriasis Palmoplantar Pustulosis Area and Severity Index (PPPASI) was 12.6 ± 8.6. Mean body mass index was above average at 27.1 ± 5.5. The PPP patients had previously received an average of 2.6 ± 2.1 different anti-psoriatic systemic drugs or UV-therapies. The systemic drugs that had been used most frequently were corticosteroids in 40.1% of patients, followed by acitretin (37.8%), and methotrexate (27.9%). The PPPASI was 13.4 ± 8.9 in patients without current systemic therapy and 10.4 ± 7.9 in patients with systemic therapy.

Conclusion: Many PPP patients had a concomitant diagnosis of psoriasis vulgaris and/or psoriatic arthritis or had a family history of psoriasis. Despite the fact that many of the patients were using anti-psoriatic therapies, there was still a high burden of disease within this PPP cohort. This insufficient control of symptoms demonstrates the urgent need for new PPP treatments.
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April 2017

Efficacy and safety of adalimumab every other week versus methotrexate once weekly in children and adolescents with severe chronic plaque psoriasis: a randomised, double-blind, phase 3 trial.

Lancet 2017 07 4;390(10089):40-49. Epub 2017 May 4.

AbbVie, North Chicago, IL, USA.

Background: Adalimumab is indicated for the treatment of moderate to severe psoriasis in adults. We assessed the efficacy and safety of adalimumab in children and adolescents with severe plaque psoriasis.

Methods: This randomised, double-blind, multiperiod, phase 3 trial was done at 38 clinics in 13 countries. Patients (aged ≥4 to <18 years) with severe plaque psoriasis who had not responded to topical therapy were randomly assigned with an interactive voice or web-response system (1:1:1) to receive adalimumab 0·8 mg/kg or 0·4 mg/kg subcutaneously at week 0, then every other week starting at week 1, or oral methotrexate once weekly (0·1-0·4 mg/kg) for 16 weeks. Randomisation was stratified by history of etanercept treatment, with a block size of three. Responders were withdrawn from treatment (for up to 36 weeks) and re-treated with adalimumab (for 16 weeks) if disease became uncontrolled. Ranked primary efficacy endpoints were the proportion of patients who achieved at least 75% improvement from baseline in Psoriasis Area and Severity Index (PASI75) score and clear or minimal physician global assessment (PGA) score at week 16, comparing adalimumab 0·8 mg/kg with methotrexate. Efficacy analysis was by intention to treat, and safety analysis included all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, number NCT01251614, and has been completed.

Findings: Between Dec 14, 2010, and Feb 5, 2015, 114 patients were randomly assigned to adalimumab 0·8 mg/kg (n=38), adalimumab 0·4 mg/kg (n=39) or methotrexate (n=37). At week 16, PASI75 was achieved in 22 (58%) of 38 patients in the adalimumab 0·8 mg/kg group compared with 12 (32%) of 37 patients in the methotrexate group (p=0·027). 23 (61%) of 38 patients in the adalimumab 0·8 mg/kg group and 15 (41%) of 37 in the methotrexate group achieved clear or minimal PGA (p=0·083). In the adalimumab 0·4 mg/kg group, 17 (44%) of 39 patients achieved PASI75 and 16 (41%) achieved clear or minimal PGA. The most frequent adverse events were infections (17 [45%] of 38 in the adalimumab 0·8 mg/kg group during initial treatment; 22 [56%] of 39 in the adalimumab 0·4 mg/kg group; 21 [57%] of 37 in the methotrexate group). Three serious adverse events were reported, all in patients in the adalimumab 0·4 mg/kg group, and were not judged to be related to study drug.

Interpretation: Treatment with adalimumab 0·8 mg/kg in children and adolescents with severe plaque psoriasis provided significant improvements in PASI75 and a non-significant increase in the proportion of patients who achieved clear or minimal PGA compared with methotrexate. No new safety risks were identified.

Funding: AbbVie.
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http://dx.doi.org/10.1016/S0140-6736(17)31189-3DOI Listing
July 2017

Risankizumab versus Ustekinumab for Moderate-to-Severe Plaque Psoriasis.

N Engl J Med 2017 04;376(16):1551-1560

From K. Papp Clinical Research and Probity Medical Research, Waterloo, ON (K.A.P.), School of Medicine, Queen's University, Kingston, ON (M.G.), and Centre for Dermatology and Probity Medical Research, Peterborough, ON (M.G.) - all in Canada; Oregon Medical Research Center, Portland (A.B.); Altman Dermatology Associates, Arlington Heights, IL (M.B.); Rockefeller University, New York (J.K.); Hôpital de l'Archet, University of Nice-Sophia Antipolis, Nice, France (J.-P.L.); Baylor Research Institute, Dallas (A.M.); Charité Universitätsmedizin Berlin, Berlin (S.P.), Boehringer Ingelheim Pharma, Biberach (B.R.B.), and Boehringer Ingelheim Pharma, Ingelheim, (S.J.P.) - all in Germany; University of Texas Health Science Center, Houston (S.T.); University of California, Los Angeles, School of Medicine, Los Angeles (H.S.); and Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT (S.V., C.P., N.B., M.F., P.S.).

Background: Interleukin-23 is thought to be critical to the pathogenesis of psoriasis. We compared risankizumab (BI 655066), a humanized IgG1 monoclonal antibody that inhibits interleukin-23 by specifically targeting the p19 subunit and thus prevents interleukin-23 signaling, and ustekinumab, an interleukin-12 and interleukin-23 inhibitor, in patients with moderate-to-severe plaque psoriasis.

Methods: We randomly assigned a total of 166 patients to receive subcutaneous injections of risankizumab (a single 18-mg dose at week 0 or 90-mg or 180-mg doses at weeks 0, 4, and 16) or ustekinumab (45 or 90 mg, according to body weight, at weeks 0, 4, and 16). The primary end point was a 90% or greater reduction from baseline in the Psoriasis Area and Severity Index (PASI) score at week 12.

Results: At week 12, the percentage of patients with a 90% or greater reduction in the PASI score was 77% (64 of 83 patients) for risankizumab (90-mg and 180-mg groups, pooled), as compared with 40% (16 of 40 patients) for ustekinumab (P<0.001); the percentage of patients with a 100% reduction in the PASI score was 45% in the pooled 90-mg and 180-mg risankizumab groups, as compared with 18% in the ustekinumab group. Efficacy was generally maintained up to 20 weeks after the final dose of 90 or 180 mg of risankizumab. In the 18-mg and 90-mg risankizumab groups and the ustekinumab group, 5 patients (12%), 6 patients (15%), and 3 patients (8%), respectively, had serious adverse events, including two basal-cell carcinomas and one major cardiovascular adverse event; there were no serious adverse events in the 180-mg risankizumab group.

Conclusions: In this phase 2 trial, selective blockade of interleukin-23 with risankizumab was associated with clinical responses superior to those associated with ustekinumab. This trial was not large enough or of long enough duration to draw conclusions about safety. (Funded by Boehringer Ingelheim; ClinicalTrials.gov number, NCT02054481 ).
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http://dx.doi.org/10.1056/NEJMoa1607017DOI Listing
April 2017

Clinical similarity of biosimilar ABP 501 to adalimumab in the treatment of patients with moderate to severe plaque psoriasis: A randomized, double-blind, multicenter, phase III study.

J Am Acad Dermatol 2017 Jun 11;76(6):1093-1102. Epub 2017 Mar 11.

Probity Medical Research, Farmington, Connecticut; University of Connecticut Health Center, Connecticut.

Background: ABP 501 is a biosimilar of adalimumab.

Objective: We sought to compare the efficacy and safety of ABP 501 with adalimumab.

Methods: This 52-week, double-blind study randomized patients with moderate to severe psoriasis to ABP 501 or adalimumab. At week 16, those with 50% or more improvement in Psoriasis Area and Severity Index score from baseline on ABP 501 continued the same treatment, whereas adalimumab-treated patients were rerandomized to adalimumab or ABP 501. Clinical similarity in Psoriasis Area and Severity Index percent improvement from baseline to week 16 (primary end point) was established if the point estimate of treatment difference and its 2-sided 95% confidence interval between groups was within equivalence margin of ±15. Patients, including those undergoing a single transition at week 16, were evaluated for safety and immunogenicity.

Results: Psoriasis Area and Severity Index percent improvement at week 16 was 80.9 for ABP 501 and 83.1 for adalimumab (least-square mean difference -2.18 [95% confidence interval -7.39 to 3.02]). Adverse events (67.2% [117/174] vs 63.6% [110/173]) and antidrug antibody incidence (55.2% [96/174] vs 63.6% [110/173]) for ABP 501 vs adalimumab were similar. Safety, including immunogenicity, was similar among groups after single transition (week 20).

Limitations: The 52-week data are not reported here.

Conclusions: ABP 501 was shown to be clinically similar to adalimumab. Safety and immunogenicity were not impacted immediately after single transition (adalimumab to ABP 501).
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http://dx.doi.org/10.1016/j.jaad.2016.12.014DOI Listing
June 2017

S1-Leitlinie zur Diagnostik und Therapie der Skabies - Kurzfassung.

J Dtsch Dermatol Ges 2016 Nov;14(11):1160-1171

Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie, Universitätsklinikum Würzburg.

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http://dx.doi.org/10.1111/ddg.13130_gDOI Listing
November 2016

S1 guidelines on the diagnosis and treatment of scabies - short version.

J Dtsch Dermatol Ges 2016 Nov;14(11):1155-1167

Department of Dermatology, Venereology and Allergology, University Hospital Würzburg.

The goals of this German guideline are the improvement of diagnosis and therapy of scabies, the implementation of a coordinated action in outbreaks of scabies, and the control of this infestation in large migration or refugee flows.Sarcoptes scabiei var. hominis is transmitted by direct skin-to-skin contact of sufficient duration. The infectivity of female mites when removed from patients does not exceed 48 hours at room temperature (21°C) and relative humidity of 40-80%. The risk of infection rises proportionally to the number of mites on the skin and is particularly high in crusted scabies. As elderly persons tend to develop crusted scabies due to disease- or medication-related immunosuppression, there is an increased risk for outbreaks of scabies at nursing homes and extended-care facilities. The guideline contains detailed recommendations for management of such outbreaks. In refugees the prevalence of scabies is higher than in the general population in Germany, but the risk for outbreaks is not high. Scabies infestation should be considered when a recent onset of itching is associated with eczema and presence of burrows or comma-like papules at predilection sites. It is confirmed by dermatoscopic detection of mites or by microscopic identification of mites, mite eggs or fecal matter (scybala) from skin scrapings.The treatment of choice for common scabies is topical permethrin 5% cream applied for 8-12 hours. Permethrin can be considered for off-label use also in infants of less than 3 months of age and pregnant women. For this group crotamiton is another option, which, besides benzyl benzoate, presents a good second line therapy for the other indications. Indications for oral ivermectin, which has just been licensed in Germany, include patients with immunosuppression, severe dermatitis, and low adherence.Crusted scabies is preferentially treated by a combination of topical permethrin and oral ivermectin. Affected patients should be isolated, and all contact persons should be treated. The guideline contains lists for additional measures, including possible treatment of contact persons, clothes, linen and other possibly infested articles.
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http://dx.doi.org/10.1111/ddg.13130DOI Listing
November 2016

Relationship between Histological and Clinical Course of Psoriasis: A Pilot Investigation by Reflectance Confocal Microscopy during Goeckerman Treatment.

Skin Pharmacol Physiol 2016 4;29(1):47-54. Epub 2016 Feb 4.

Department of Dermatology, Venereology and Allergology, Charitx00E9; - Universitx00E4;tsmedizin Berlin, Berlin, Germany.

Alterations of the skin microvasculature are known to play an important role in the development and maintenance of psoriatic skin lesions. In this study, we investigated lesional skin in 11 psoriatic patients during a modified Goeckerman treatment using reflectance confocal microscopy (RCM) to study the relationship between clinical clearance and histological normalization of psoriatic skin and the significance of histological abnormalities on the course of disease. The treatment regimen resulted in a significant reduction of the Psoriasis Area and Severity Index (PASI) as well as capillary and papillary diameters (p < 0.0001). The capillary and papillary diameters were still enlarged when compared to those in normal skin (p < 0.001). Capillary and papillary diameters correlated with each other prior to and after treatment (correlation coefficient = 0.63 and 0.64, p = 0.01 and 0.002, respectively) but not with the PASI. Capillary and papillary diameters after treatment and percentage reduction of the PASI during treatment seemed to be better predictors for the clinical course of relapse than the PASI after treatment. These findings make the subclinical changes of psoriatic skin vessels and dermal papillae a legitimate target for treatment. Further investigations of a large group of patients are needed to evaluate the potential of RCM findings as successor of the PASI in the monitoring of psoriasis.
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http://dx.doi.org/10.1159/000443211DOI Listing
November 2016