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Psoriasis: HELP
Articles by Joerg Christoph Prinz
Based on 45 articles published since 2008
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Between 2008 and 2019, J. Prinz wrote the following 45 articles about Psoriasis.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Review Melanocytes: Target Cells of an HLA-C*06:02-Restricted Autoimmune Response in Psoriasis. 2017

Prinz, Jörg Christoph. ·Department of Dermatology, University Clinics, Ludwig Maximilian University of Munich, Munich, Germany. Electronic address: joerg.prinz@med.uni-muenchen.de. ·J Invest Dermatol · Pubmed #28941475.

ABSTRACT: HLA-C*06:02 is the main psoriasis risk allele. By the unbiased analysis of a Vα3S1/Vβ13S1 T-cell receptor from pathogenic psoriatic CD8

2 Review Autoimmune aspects of psoriasis: Heritability and autoantigens. 2017

Prinz, Jörg Christoph. ·Department of Dermatology, University Clinics, Ludwig-Maximilian-University of Munich, Munich, Germany. Electronic address: joerg.prinz@med.uni-muenchen.de. ·Autoimmun Rev · Pubmed #28705779.

ABSTRACT: Chronic immune-mediated disorders (IMDs) constitute a major health burden. Understanding IMD pathogenesis is facing two major constraints: Missing heritability explaining familial clustering, and missing autoantigens. Pinpointing IMD risk genes and autoimmune targets, however, is of fundamental importance for developing novel causal therapies. The strongest association of all IMDs is seen with human leukocyte antigen (HLA) alleles. Using psoriasis as an IMD model this article reviews the pathogenic role HLA molecules may have within the polygenic predisposition of IMDs. It concludes that disease-associated HLA alleles account for both missing heritability and autoimmune mechanisms by facilitating tissue-specific autoimmune responses through autoantigen presentation.

3 Review The role of IL-23 and the IL-23/T 2017

Girolomoni, G / Strohal, R / Puig, L / Bachelez, H / Barker, J / Boehncke, W H / Prinz, J C. ·Section of Dermatology, Department of Medicine, University of Verona, Verona, Italy. · Department of Dermatology and Venerology, Federal Academic Teaching Hospital of Feldkirch, Feldkirch, Austria. · Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain. · Sorbonne Paris Cité, Université Paris Diderot, Paris, France. · Department of Dermatology, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France. · UMR INSERM U1163, Institut Imagine, Paris, France. · St John's Institute of Dermatology, King's College London, London, UK. · Division of Dermatology, Geneva University Hospitals, Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland. · Department of Dermatology, University of Munich, Munich, Germany. ·J Eur Acad Dermatol Venereol · Pubmed #28653490.

ABSTRACT: Psoriasis is a chronic, immune-mediated disease affecting more than 100 million people worldwide and up to 2.2% of the UK population. The aetiology of psoriasis is thought to originate from an interplay of genetic, environmental, infectious and lifestyle factors. The manner in which genetic and environmental factors interact to contribute to the molecular disease mechanisms has remained elusive. However, the interleukin 23 (IL-23)/T-helper 17 (T

4 Review [Autoimmune reactions in psoriasis : Spotlight]. 2016

Prinz, J C. ·Klinik und Poliklinik für Dermatologie und Allergologie, Klinikum der Universität München, Ludwig-Maximilians-Universität, Frauenlobstr. 9-11, 80337, München, Deutschland. joerg.prinz@med.uni-muenchen.de. ·Hautarzt · Pubmed #27178039.

ABSTRACT: BACKGROUND: Psoriasis is a human leukocyte antigen (HLA)-associated T‑cell-mediated disorder. OBJECTIVES: The role of the main psoriasis risk allele HLA-C*06:02 in disease manifestation and the mechanisms which activate the pathogenic T‑cell response in the skin of psoriasis patients remained elusive. MATERIALS AND METHODS: Key to the immune pathogenesis of psoriasis was the analysis of the specificity of the infiltrating lesional psoriatic CD8(+) T cells RESULTS AND CONCLUSION: Analyses of the lesional psoriatic T‑cell reactivity demonstrate that psoriasis is an autoimmune disease. It is based on an autoimmune response against melanocytes which is preferentially mediated by HLA-C*06:02 through autoantigen presentation. Here we discuss the mechanisms of this autoimmune response in the context of the polygenic psoriatic predisposition.

5 Review Treatment of psoriasis with etanercept: the typical patient profile. 2016

Prinz, J C / Puig, L / Girolomoni, G. ·Department of Dermatology, University of Munich, Munich, Germany. · Department of Dermatology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Catalonia, Spain. · Section of Dermatology, Department of Medicine, University of Verona, Piazzale A. Stefani, Verona, Italy. ·J Eur Acad Dermatol Venereol · Pubmed #27073046.

ABSTRACT: The chronic nature of psoriasis means that patients often require lifetime treatment. Over this time, treatment frequently has to be adapted to meet variable demands resulting from changes in life course and life events. Biological drugs used to treat psoriasis vary in their dosing regimens, convenience and flexibility. Dermatologists need to understand which biologic agent is best suited for each individual patient. A wealth of evidence supports the safe and effective use of etanercept, which offers a rapid and sustained response, flexibility of dosing, maintenance of response after dose reduction or interruption, and efficacy against non-skin manifestations such as psoriatic arthritis. An expert panel met to agree the typical patient profile of a psoriasis patient treated with etanercept, the main benefits of etanercept in psoriasis, and the patient group most likely to benefit from its use. They agreed that flexibility of dosing, the potential to individualize therapy by stopping and starting treatment while maintaining efficacy, and the possibility of cost saving through the use of flexible treatment regimens were important benefits supporting the use of etanercept in many patients with psoriasis.

6 Review A patient-centred approach to biological treatment decision making for psoriasis: an expert consensus. 2015

Strohal, R / Prinz, J C / Girolomoni, G / Nast, A. ·Department of Dermatology and Venerology, Federal Academic Teaching Hospital of Feldkirch, Feldkirch, Austria. · Department of Dermatology, University of Munich, Munich, Germany. · Section of Dermatology, Department of Medicine, University of Verona, Verona, Italy. · Division of Evidence Based Medicine (dEBM), Department of Dermatology, Charité - Universitätsmedizin Berlin, Berlin, Germany. ·J Eur Acad Dermatol Venereol · Pubmed #26370908.

ABSTRACT: BACKGROUND: Each individual psoriasis patient has different expectations and goals for biological treatment, which may differ from those of the clinician. As such, a patient-centred approach to treatment goals remains an unmet need in psoriasis. OBJECTIVE: The aim of this study was to review available data on patients' and physicians' decision criteria and expectations of biological treatment for moderate-to-severe psoriasis with the aim of developing a core set of questions for clinicians to ask patients routinely to understand what is important to them and thus better align physicians' and patients' expectations of treatment with biologics and its outcomes. METHODS: A literature search was conducted to identify key themes and data gaps. Aspects of treatment relevant when choosing a biological agent for an individual patient were identified and compared to an existing validated instrument. A series of questions aimed at helping the physician to identify the particular aspects of treatment that are recognised as important to individual psoriasis patients was developed. RESULTS: Key findings of the literature search were grouped under themes of adherence, decision-making, quality of life, patient/physician goals, communication, patient-reported outcomes, satisfaction and patient benefit index. Several aspects of treatment were identified as being relevant when choosing a biological agent for an individual patient. The questionnaire is devised in two parts. The first part asks questions about patients' experience of psoriasis and satisfaction with previous treatments. The second part aims to identify the treatment attributes patients consider to be important and may as such affect their preference for a particular biological treatment. The questionnaire results will allow the physician to understand the key factors that can be influenced by biological drug choice that are of importance to the patient. This information can be used be the physician in clinical decision making. CONCLUSION: The questionnaire has been developed to provide a new tool to better understand and align patients' and physicians' preferences and goals for biological treatment of psoriasis.

7 Review Practical guidance on immunogenicity to biologic agents used in the treatment of psoriasis: What can be learnt from other diseases? 2015

Lambert, Jo / Nast, Alexander / Nestle, Frank O / Prinz, Jörg C. ·a Department of Dermatology , Ghent University Hospital , Ghent , Belgium . · b Division of Evidence Based Medicine (dEBM), Department of Dermatology, Venerology and Allergy , Charité - Universitätsmedizin Berlin , Berlin , Germany . · c St. John's Institute of Dermatology, King's College London School of Medicine , London , UK , and. · d Clinic and Policlinic for Dermatology and Allergology, Ludwig-Maximilian-University , Munich , Germany. ·J Dermatolog Treat · Pubmed #26108443.

ABSTRACT: The clinical efficacy of biologic agents for the treatment of moderate to severe psoriasis is well proven in clinical studies, but patients may lose response over time. Loss of response may be due to immunogenicity and the formation of anti-drug antibodies (ADA). Although data on the immunogenicity of drugs used to treat psoriasis are now emerging, more information on the impact of factors, such as dosing regimens and concomitant immunosuppressive therapy is needed. Exploring research from other disease areas where immunogenicity has long been recognised as a significant clinical issue may help in developing future strategies for using drug level and ADA measurements to help tailor biologic therapy to meet individual needs. To this end, we analyse what is known about biologics and immunogenicity in psoriasis. In order to learn from other indications, we then address the issue of immunogenicity for three different types of biologic treatments. First, factor VIII-substitution in haemophilia, where the immune system is newly exposed to a physiologic but formerly absent protein. Second, the use of biologics in inflammatory bowel disease, where similar treatment challenges apply as observed in psoriasis. Third, immunogenicity in multiple sclerosis caused by therapeutic antibodies or interferons. Immunogenicity strategies used in other disease areas will need to be tested in psoriasis before they can be widely adopted in routine clinical practice.

8 Review Immunogenicity of biotherapy used in psoriasis: the science behind the scenes. 2015

Jullien, Denis / Prinz, Jörg C / Nestle, Frank O. ·Department of Dermatology, Faculty of Medicine, Hôpital Edouard Herriot, University of Lyon, Lyon, France. Electronic address: denis.jullien@chu-lyon.fr. · Clinic for Dermatology and Allergology, Ludwig-Maximilians-University, Munich, Germany. · St. John's Institute of Dermatology, King's College London School of Medicine, London, UK. ·J Invest Dermatol · Pubmed #25120005.

ABSTRACT: A potential limitation in the use of biologic drugs used to treat psoriasis is the development of anti-drug antibodies (ADAs). Many factors contribute to this unwanted immune response, from the product itself, to its mode of administration, the underlying disease, and patient characteristics. ADAs may decrease the efficacy of biologic drugs by neutralizing them or modifying their clearance and may account for hypersensitivity reactions. This article reviews the scientific basis of immunogenicity and the mechanisms by which it affects clinical outcomes. It also considers testing for immunogenicity and how biologic therapy of psoriasis may be tailored on the basis of immunogenicity.

9 Review Early intervention in psoriasis and immune-mediated inflammatory diseases: A hypothesis paper. 2015

Girolomoni, G / Griffiths, C E M / Krueger, J / Nestle, F O / Nicolas, J-F / Prinz, J C / Puig, L / Ståhle, M / van de Kerkhof, P C M / Allez, M / Emery, P / Paul, C. ·Department of Medicine, Section of Dermatology and Venereology, University of Verona , Verona , Italy . ·J Dermatolog Treat · Pubmed #24547907.

ABSTRACT: Psoriasis is an immune-mediated inflammatory disease (IMID) which may have a major impact on a patient's life, especially when the disease is moderate to severe. There is evidence that treatment of psoriasis during the first years is conservative and frequently based on topical agents which rarely clear lesions. Treatment with systemic agents including biologics is often undertaken only when topical agents have proved unsuitable, even in patients with moderate to severe disease. However, there is evidence that in other IMIDs (rheumatoid arthritis and Crohn's disease), targeted systemic treatment given early in the treatment pathway may improve long-term patient outcomes. We hypothesize that a patient-centered therapeutic approach, undertaken early in the psoriasis treatment pathway ("early intervention") with the goal of complete clearance, may improve control of cutaneous symptoms and may also modify disease course and burden. Critical points to address when designing an early intervention study would include: the definition of psoriasis disease activity; patient selection; intervention selection; and dosing strategies.

10 Review Clinical relevance of immunogenicity of biologics in psoriasis: implications for treatment strategies. 2014

Carrascosa, J-M / van Doorn, M B A / Lahfa, M / Nestle, F O / Jullien, D / Prinz, J C. ·Department of Dermatology, Hospital Universitari Germans Trias i Pujol, Barcelona, Spain. ·J Eur Acad Dermatol Venereol · Pubmed #24841895.

ABSTRACT: Biological drugs such as the tumour necrosis factor inhibitors have revolutionized the treatment of psoriasis, but some have the potential to induce an unwanted immune response. This immunogenicity may be associated with low trough drug levels, reduced clinical efficacy, reduced drug survival and an increased risk for adverse events. This article presents a literature review of the evidence on immunogenicity of biologics used in the treatment of psoriasis and considers the implications for therapeutic decision-making in the management of patients with moderate-to-severe psoriasis.

11 Review Etanercept-induced injection site reactions: potential pathomechanisms and clinical assessment. 2012

Batycka-Baran, Aleksandra / Flaig, Michael / Molin, Sonja / Ruzicka, Thomas / Prinz, Joerg C. ·Ludwig-Maximilian University, Department of Dermatology and Allergology, Munich, Germany. joerg.prinz@med.uni-muenchen.de ·Expert Opin Drug Saf · Pubmed #22998733.

ABSTRACT: INTRODUCTION: Etanercept (ETN) is a tumor necrosis factor alpha (TNF-α) antagonist used for the treatment of chronic inflammatory disorders. Injection site reactions (ISRs) are reported to be the most common adverse event of ETN therapy. While their mechanisms are not completely understood, the occurrence of ETN-ISRs could indicate a risk of systemic immune-mediated severe adverse drug reactions. AREAS COVERED: Based on two cases and a review of the literature, the characteristics and frequency of ETN-ISRs were assessed. This article discusses their potential mechanisms and clinical relevance, and provides recommendations for the management of patients presenting with ETN-ISRs. EXPERT OPINION: Basically, irritative and immune-mediated ISRs may be distinguished. The formation of anti-drug antibodies (ADAs) may promote immune-mediated ISRs that likely represent either anaphylactic type I reactions, or cutaneous Arthus-like type III reactions according to the Coombs and Gell classification. A differentiation between these reactions by clinical course and etanercept-skin testing may help to decide if ETN treatment should be stopped to avoid the development of more severe adverse drug reactions if ISRs occur.

12 Review [Comorbidities in psoriasis]. 2010

Weisenseel, P / Prinz, J C. ·Klinik und Poliklinik für Dermatologie und Allergologie der Ludwig-Maximilians-Universität München. pweisens@its.jnj.com ·Dtsch Med Wochenschr · Pubmed #20614408.

ABSTRACT: -- No abstract --

13 Review [Biologics. New drugs, new adverse reactions]. 2010

Prinz, J C. ·Klinik und Poliklinik für Dermatologie und Allergologie, Ludwig-Maximilians-Universität, Frauenlobstr. 9-11, 80337, München, Deutschland. joerg.prinz@med.uni-muenchen.de ·Hautarzt · Pubmed #20585746.

ABSTRACT: Biologics have been available in Germany for the treatment of moderate to severe chronic plaque psoriasis and/or psoriatic arthritis since 2004. They include chimeric (human/mouse) or fully human monoclonal antibodies or recombinant fusion proteins. The currently available biologics are cytokine antagonists, which neutralize either TNF-alpha or the interleukins IL-12 and IL-23. Unexpected adverse events result either from their potential immunogenicity or from their mode of action, which consists in neutralizing the biologic activity of the respective cytokines. In particular the increased risk for severe infections that may take an atypical course during biologic therapy deserves attention in daily clinical practice.

14 Review Psoriasis and systemic inflammatory diseases: potential mechanistic links between skin disease and co-morbid conditions. 2010

Davidovici, Batya B / Sattar, Naveed / Prinz, Jörg C / Puig, Luis / Emery, Paul / Barker, Jonathan N / van de Kerkhof, Peter / Ståhle, Mona / Nestle, Frank O / Girolomoni, Giampiero / Krueger, James G. ·Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, USA. ·J Invest Dermatol · Pubmed #20445552.

ABSTRACT: Psoriasis is now classified as an immune-mediated inflammatory disease (IMID) of the skin. It is being recognized that patients with various IMIDs, including psoriasis, are at higher risk of developing "systemic" co-morbidities, e.g., cardiovascular disease (CVD), metabolic syndrome, and overt diabetes. In non-psoriatic individuals, the pathophysiology of obesity, aberrant adipocyte metabolism, diabetes, and CVDs involves immune-mediated or inflammatory pathways. IMIDs may impact these co-morbid conditions through shared genetic risks, common environmental factors, or common inflammatory pathways that are co-expressed in IMIDs and target organs. Given that pathogenic immune pathways in psoriasis are now well worked out and a large number of inflammatory mediators have been identified in skin lesions, in this review we will consider possible mechanistic links between skin inflammation and increased risks of (1) obesity or metabolic alterations and (2) CVD. In particular, we will discuss how well-established risk factors for CVD can originate from inflammation in other tissues.

15 Review [The role of streptococci in psoriasis]. 2009

Prinz, J C. ·Klinik und Poliklinik für Dermatologie und Allergologie, Ludwig-Maximilians-Universität, Frauenlobstrasse 9-11, Munich, Germany. joerg.prinz@med.uni-muenchen.de ·Hautarzt · Pubmed #19151963.

ABSTRACT: Infections with Streptococcus pyogenes are highly relevant among the environmental factors that contribute to first onset or relapses of psoriasis in predisposed individuals. Streptococcal angina or pharyngitis, but also perianal streptococcal dermatitis, vulvovaginitis or balanoposthitis are potential causes. Several mechanisms such as molecular mimicry or superantigens may be involved. Many patients develop a chronic streptococcal infection or colonization that may result from the ability of streptococci for intracellular uptake and persistence in epithelial cells. Whether and under what conditions a curative treatment of streptococcal infection by tonsillectomy or antibiotic treatment may affect the course of psoriasis, as proposed by several observations, needs to be determined in more detail by clinical trials.

16 Review Targeting the interleukin-12/23 cytokine family in the treatment of psoriatic disease. 2008

Shear, Neil H / Prinz, Jörg / Papp, Kim / Langley, Richard G B / Gulliver, Wayne P. ·University of Toronto, Ontario, Canada. ·J Cutan Med Surg · Pubmed #19886505.

ABSTRACT: Psoriasis is a complex systemic immune inflammatory disease whose burden of disease includes poorer quality of life, a high prevalence of serious comorbidities, and a potentially decreased life span-hence the continued need to search for new treatment options. ABT-874 (Abbott Laboratories, Saint-Laurent, QC,) and ustekinumab (CNTO 1275, Ortho Biotech, Toronto, ON) are two monoclonal antibodies against interleukins 12 and 23 (IL-12/23), key mediators of T-cell differentiation in the pathogenesis of psoriasis. The results of a 12-week, phase II, dose-finding study of ABT-874 have been encouraging. More recently, level 1 evidence has emerged for ustekinumab in two placebo-controlled phase III trials, PHOENIX 1 and PHOENIX 2; therapeutic responses to ustekinumab have been maintained up to 76 weeks of follow-up, and quality of life has significantly improved with ustekinumab. Both agents produced few and mild adverse events, and the rates of serious infections and cancers were very low and similar to those of placebo. These promising results strongly confirm the central role of IL-12/23 in psoriasis and its importance as a therapeutic target.

17 Clinical Trial Secukinumab Self-Administration by Prefilled Syringe Maintains Reduction of Plaque Psoriasis Severity Over 52 Weeks: Results of the FEATURE Trial. 2016

Gottlieb, Alice B / Blauvelt, Andrew / Prinz, Jörg C / Papanastasiou, Philemon / Pathan, Rashidkhan / Nyirady, Judit / Fox, Todd / Papavassilis, Charis. · ·J Drugs Dermatol · Pubmed #27741340.

ABSTRACT: BACKGROUND: Secukinumab, a human monoclonal antibody that selectively targets interleukin-17A, is highly efficacious in the treatment of moderate-to-severe psoriasis, starting at early time points, with a sustained effect and a favorable safety profile. METHODS: Patients with moderate-to-severe plaque psoriasis were randomized to secukinumab 300 mg, secukinumab 150 mg, or placebo self-administered by prefilled syringe at baseline, weeks 1, 2, and 3, and then every four weeks from week 4 to 48. Efficacy responses (≥ 75/90/100% improvement in Psoriasis Area and Severity Index [PASI 75/90/100] and clear/almost clear skin by Investigator's Global Assessment 2011 modified version [IGA mod 2011 0/1]) were measured to week 52. Patient-reported usability of the prefilled syringe was evaluated by the Self-Injection Assessment Questionnaire to week 48. RESULTS: The efficacy of secukinumab increased to week 16 and was maintained to week 52. With secukinumab 300 mg at week 52, PASI 75/90/100 and IGA mod 2011 0/1 responses were achieved by 83.5%/68.0%/47.5% and 71.5% of patients when analyzed by multiple imputation, respectively, and by 75.9%/62.1%/43.1% and 63.8% of patients when analyzed by nonresponder imputation, respectively. With secukinumab 150 mg at week 52, PASI 75/90/100 and IGA mod 2011 0/1 responses were achieved by 63.5%/50.3%/31.1% and 43.6% of patients when analyzed by multiple imputation, respectively, and by 61.0%/49.2%/30.5% and 42.4% of patients when analyzed by nonresponder imputation, respectively. Self-reported acceptability of the prefilled syringe was high throughout the study. The incidence of adverse events (AE) was well balanced between groups, with AEs reported in 74.4% of patients receiving secukinumab 300 mg and 77.3% of patients receiving secukinumab 150 mg. Nasopharyngitis was the most common AE across both secukinumab groups. CONCLUSION: Self-administration of secukinumab by prefilled syringe was associated with robust and sustained efficacy and a favorable safety profile up to week 52.

J Drugs Dermatol. 2016;15(10):1226-1234.

18 Clinical Trial A Phase 2 Trial of Guselkumab versus Adalimumab for Plaque Psoriasis. 2015

Gordon, Kenneth B / Duffin, Kristina Callis / Bissonnette, Robert / Prinz, Jörg C / Wasfi, Yasmine / Li, Shu / Shen, Yaung-Kaung / Szapary, Philippe / Randazzo, Bruce / Reich, Kristian. ·From the Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago (K.B.G.) · the Department of Dermatology, University of Utah School of Medicine, Salt Lake City (K.C.D.) · Innovaderm Research, Montreal (R.B.) · the Department of Dermatology, Ludwig-Maximilians-Universität München, Munich (J.C.P.), and the Dermatologikum Hamburg, Hamburg (K.R.) - both in Germany · and Janssen Research and Development, Spring House (Y.W., S.L., Y.-K.S., P.S., B.R.), and the Department of Dermatology, University of Pennsylvania, Philadelphia (B.R.) - both in Pennsylvania. ·N Engl J Med · Pubmed #26154787.

ABSTRACT: BACKGROUND: Little is known about the effect of specific anti-interleukin-23 therapy, as compared with established anti-tumor necrosis factor therapies, for the treatment of moderate-to-severe plaque psoriasis. METHODS: In a 52-week, phase 2, dose-ranging, randomized, double-blind, placebo-controlled, active-comparator trial, we compared guselkumab (CNTO 1959), an anti-interleukin-23 monoclonal antibody, with adalimumab in patients with moderate-to-severe plaque psoriasis. A total of 293 patients were randomly assigned to receive guselkumab (5 mg at weeks 0 and 4 and every 12 weeks thereafter, 15 mg every 8 weeks, 50 mg at weeks 0 and 4 and every 12 weeks thereafter, 100 mg every 8 weeks, or 200 mg at weeks 0 and 4 and every 12 weeks thereafter) through week 40, placebo, or adalimumab (standard dosage for psoriasis). At week 16, patients in the placebo group crossed over to receive guselkumab at a dose of 100 mg every 8 weeks. The primary end point was the proportion of patients with a Physician's Global Assessment (PGA) score of 0 (indicating cleared psoriasis) or 1 (indicating minimal psoriasis) at week 16. RESULTS: At week 16, the proportion of patients with a PGA score of 0 or 1 was significantly higher in each guselkumab group than in the placebo group: 34% in the 5-mg group, 61% in the 15-mg group, 79% in the 50-mg group, 86% in the 100-mg group, and 83% in the 200-mg group, as compared with 7% in the placebo group (P≤0.002 for all comparisons). Moreover, the proportion was significantly higher in the 50-mg, 100-mg, and 200-mg guselkumab groups than in the adalimumab group (58%) (P<0.05 for all comparisons). At week 16, the proportion of patients with at least a 75% improvement in Psoriasis Area and Severity Index scores was significantly higher in each guselkumab group than in the placebo group (P<0.001 for all comparisons). At week 40, the proportion of patients with a PGA score of 0 or 1 remained significantly higher in the 50-mg, 100-mg, and 200-mg guselkumab groups than in the adalimumab group (71%, 77%, and 81%, respectively, vs. 49%) (P<0.05 for all comparisons). Between week 0 and week 16, infections were observed in 20% of the patients in the guselkumab groups, 12% in the adalimumab group, and 14% in the placebo group. CONCLUSIONS: The results of this phase 2 trial suggest that guselkumab may be an effective therapy for plaque psoriasis and that control of psoriasis can be achieved with specific anti-interleukin-23 therapy. (Funded by Janssen Research and Development; X-PLORE ClinicalTrials.gov number, NCT01483599.).

19 Clinical Trial Long-term efficacy and safety of ustekinumab, with and without dosing adjustment, in patients with moderate-to-severe psoriasis: results from the PHOENIX 2 study through 5 years of follow-up. 2015

Langley, R G / Lebwohl, M / Krueger, G G / Szapary, P O / Wasfi, Y / Chan, D / Hsu, M C / You, Y / Poulin, Y / Korman, N / Prinz, J C / Reich, K / Anonymous1220809. ·Dalhousie University, 4195 Dickson Building, 5820 University Avenue, Halifax, NS, Canada. · Icahn School of Medicine at Mount Sinai, New York, NY, U.S.A. · University of Utah Health Sciences Center, Salt Lake City, UT, U.S.A. · Janssen Research & Development, LLC, Spring House, PA, U.S.A. · Centre de Recherche Dermatologique du Quebec Metropolitain, Universite Laval, Quebec City, QC, Canada. · University Hospitals Case Medical Center, Cleveland, OH, U.S.A. · University of Munich, Munich, Germany. · Dermatologikum Hamburg, Hamburg, Germany. ·Br J Dermatol · Pubmed #25307931.

ABSTRACT: BACKGROUND: Evaluation of the dosing flexibility and long-term efficacy of biological agents is limited. OBJECTIVES: To evaluate the long-term efficacy and safety of ustekinumab with and without dosing adjustment in the 5-year PHOENIX 2 study. METHODS: Patients were randomized to placebo or ustekinumab (45 or 90 mg) at weeks 0, 4, then every 12 weeks; patients receiving placebo crossed-over at week 12. Dosing adjustments were permitted at/beyond week 28 for early adjusters (weeks 28 or 40 per response); late adjusters (during long-term extension per investigator judgement); and nonadjusters (maintained randomized treatment throughout the study). Efficacy and safety were evaluated through weeks 244 and 264, respectively. RESULTS: In the overall population, 70% (849 of 1212) of ustekinumab-treated patients completed treatment through week 244, with high proportions of patients responding to the 45-mg and 90-mg doses, respectively: 75% improvement in Psoriasis Area and Severity Index (PASI 75) (76·5% and 78·6%) and PASI 90 (50·0% and 55·5%). Approximately 20% of patients were early adjusters, 30% were late adjusters and 50% were nonadjusters. Approximately half of the late adjusters initiated adjustments after already achieving PASI 75. Improved response was generally observed following dosing adjustments. Through week 264, safety event rates did not increase and event rates were generally comparable between dose groups and between patients with and without dosing adjustment. CONCLUSIONS: Treatment with ustekinumab for up to 5 years was safe and effective. Improved response was generally demonstrated following dosing adjustments; further investigations are required to quantify actual incremental benefits. The results also suggest that some patients may desire treatment goals beyond PASI 75.

20 Clinical Trial Secukinumab administration by pre-filled syringe: efficacy, safety and usability results from a randomized controlled trial in psoriasis (FEATURE). 2015

Blauvelt, A / Prinz, J C / Gottlieb, A B / Kingo, K / Sofen, H / Ruer-Mulard, M / Singh, V / Pathan, R / Papavassilis, C / Cooper, S / Anonymous4400803. ·Oregon Medical Research Center, 9495 SW Locust Street, Suite G, Portland, OR, 97223, U.S.A. ·Br J Dermatol · Pubmed #25132411.

ABSTRACT: BACKGROUND: Secukinumab, a fully human anti-interleukin-17A monoclonal antibody, demonstrated efficacy and safety in moderate-to-severe plaque psoriasis when administered via subcutaneous injection. Self-administration by pre-filled syringe (PFS) can offer patients clinical benefits of a drug, with increased convenience. OBJECTIVES: To assess efficacy, safety and usability of secukinumab administration via PFS in subjects with moderate-to-severe plaque psoriasis. MATERIALS AND METHODS: Subjects in this phase 3 trial were randomized 1 : 1 : 1 to secukinumab 300 or 150 mg or matching placebo. Results to week 12 are presented here. Each treatment was delivered using a PFS once weekly to week 4, and again at week 8. Co-primary endpoints were secukinumab superiority over placebo for week 12 PASI 75 (≥ 75% reduction in Psoriasis Area and Severity Index) and IGA mod 2011 (2011 modified Investigator's Global Assessment) 0/1 response rates. Secondary endpoints included PFS usability, determined by observer rating of successful, hazard-free self-injection and subject rating of acceptability by the Self-Injection Assessment Questionnaire (SIAQ). RESULTS: Co-primary endpoints were met, with demonstration of superiority for each secukinumab dose vs. placebo at week 12 (PASI 75: 75·9%, 69·5% and 0% for secukinumab 300 mg, 150 mg and placebo; IGA mod 2011 0/1: 69·0%, 52·5% and 0%, respectively; P < 0·0001 for all comparisons vs. placebo). PFS usability was high: 100% of subjects successfully self-administered treatment at week 1, and subjects reported high SIAQ-assessed acceptability of the PFS throughout the trial. No new/unexpected safety signals were observed. CONCLUSIONS: Secukinumab administration by PFS was effective, with an acceptable safety profile and high usability. The PFS provides a reliable, convenient form of secukinumab administration in subjects with moderate-to-severe plaque psoriasis.

21 Clinical Trial Long-term safety experience of ustekinumab in patients with moderate-to-severe psoriasis (Part I of II): results from analyses of general safety parameters from pooled Phase 2 and 3 clinical trials. 2012

Lebwohl, Mark / Leonardi, Craig / Griffiths, Christopher E M / Prinz, Jörg C / Szapary, Philippe O / Yeilding, Newman / Guzzo, Cynthia / Li, Shu / Hsu, Ming-Chun / Strober, Bruce. ·Mount Sinai School of Medicine, New York City, New York 10029, USA. Lebwohl@aol.com ·J Am Acad Dermatol · Pubmed #21930328.

ABSTRACT: BACKGROUND: Ustekinumab targets interleukin (IL)-12 and IL-23 in the treatment of moderate-to-severe psoriasis. OBJECTIVE: To evaluate overall pooled study data to assess the safety profile of ustekinumab through 3 years of treatment. METHODS: Cumulative safety data were pooled from studies in 3117 ustekinumab-treated patients. RESULTS: During the placebo-controlled periods (Phase 2, PHOENIX 1, PHOENIX 2), rates of adverse events (AEs) were comparable among patients treated with placebo (50.4%), with ustekinumab 45 mg (57.6%), or with ustekinumab 90 mg (51.6%); similar findings were observed during the controlled period of the ACCEPT trial (etanercept: 70.0%; ustekinumab 45 mg: 66.0%; and ustekinumab 90 mg: 69.2%). Rates of serious AEs (SAEs) through the controlled periods were low and comparable among all groups (1.2% to 1.9%). Through 3 years, rates of AEs per 100 patient-years of follow-up (/100 patient-yrs) (45 mg: 305.2/100 patient-yrs; 90 mg: 305.9/100 patient-yrs) and SAEs (45 mg: 6.8/100 patient-yrs; 90 mg: 8.2/100 patient-yrs) were comparable between ustekinumab doses. No cases of demyelination or tuberculosis were reported in these trials. No dose response in rates of AEs, overall infections, or SAEs was apparent through 3 years. Rates of AEs, infections, SAEs, and AEs leading to study agent discontinuation remained generally stable or decreased over time. LIMITATIONS: Controlled periods did not extend beyond 12 to 20 weeks. Only 1247 of the 3117 ustekinumab-treated patients were treated for 2 or more years. CONCLUSIONS: The safety profile of continued ustekinumab exposure through up to 3 years is favorable and consistent with previous short-term reports.

22 Article Unopposed IL-36 Activity Promotes Clonal CD4 2018

Arakawa, Akiko / Vollmer, Sigrid / Besgen, Petra / Galinski, Adrian / Summer, Burkhard / Kawakami, Yoshio / Wollenberg, Andreas / Dornmair, Klaus / Spannagl, Michael / Ruzicka, Thomas / Thomas, Peter / Prinz, Jörg C. ·Department of Dermatology and Allergology, University Hospital, Ludwig-Maximilian-University, Munich, Germany. Electronic address: Akiko.Arakawa@med.uni-muenchen.de. · Department of Dermatology and Allergology, University Hospital, Ludwig-Maximilian-University, Munich, Germany. · Institute of Clinical Neuroimmunology, University Hospital, Ludwig-Maximilian-University, Munich, Germany. · Laboratory of Immunogenetics and Molecular Diagnostics, University Hospital, Ludwig-Maximilian-University, Munich, Germany. · Department of Dermatology and Allergology, University Hospital, Ludwig-Maximilian-University, Munich, Germany. Electronic address: joerg.prinz@med.uni-muenchen.de. ·J Invest Dermatol · Pubmed #29288651.

ABSTRACT: Generalized pustular psoriasis (GPP) is the most severe psoriasis variant. Mutations in the IL-36 antagonist IL36RN, in CARD14 or AP1S3 provide genetic evidence for autoinflammatory etiology but cannot explain its pathogenesis completely. Here we demonstrate that unopposed IL-36 signaling promotes antigen-driven and likely pathogenic T-helper type 17 (Th17) responses in GPP. We observed that CD4

23 Article The effect of phototherapy on systemic inflammatory process in patients with plaque psoriasis. 2016

Batycka-Baran, Aleksandra / Besgen, Petra / Wolf, Ronald / Szepietowski, Jacek C / Prinz, Joerg C. ·Department of Dermatology, Venereology and Allergology, Wroclaw Medical University, Wroclaw, Poland. Electronic address: aleksandra.batycka-baran@umed.wroc.pl. · Department of Dermatology and Allergology, Ludwig-Maximilian University, Munich, Germany. · Department of Dermatology, Venereology and Allergology, Wroclaw Medical University, Wroclaw, Poland. ·J Photochem Photobiol B · Pubmed #27314537.

ABSTRACT: Psoriasis is a common, chronic immune-mediated inflammatory disease. The inflammatory process in psoriasis has systemic effects and may influence the development of psoriatic comorbidities. The systemic action of phototherapy in patients with psoriasis has been so far poorly elucidated. We aimed to investigate the expression of genes encoding selected psoriasis-related cytokines in peripheral blood mononuclear cells (PBMCs) isolated from patients with psoriasis before and after treatment with phototherapy. 17 patients with mild to moderate plaque psoriasis were treated with narrow band-UVB (NB-UVB), 8 patients with moderate to severe plaque psoriasis with bath-psoralen-ultraviolet A therapy (PUVA). PBMCs were isolated by Ficoll gradient density centrifugation. Expression of genes encoding TNF-α, IL-17A, IL-6, IL-1 β, INF-γ, and IL-10 in PBMCs of patients with psoriasis before and after phototherapy was analyzed with quantitative RT-PCR. Treatment with NB-UVB therapy led to a significant decrease in IL-17A, TNF-α, and IL-6 mRNA levels in PBMCs (p=0.003; p=0.042; p=0.019, respectively). Following treatment with bath-PUVA therapy, we observed a significant decrease in TNF-α and IL-6 mRNA levels in PBMCs (p=0.031, p=0.035, respectively). Treatment with phototherapy in patients with psoriasis may affect systemic inflammation by downregulation of the expression of genes encoding proinflammatory cytokines in PBMCs, implicated in the development of psoriasis and psoriatic comorbidities.

24 Article [Psoriasis migrans : Erythema migrans as Koebner phenomenon in psoriasis]. 2016

Ständer, S / Ständer, M / Thomas, P / Prinz, J C / Wolf, R. ·Klinik und Poliklinik für Dermatologie und Allergologie der LMU, Frauenlobstraße 9-11, 80337, München, Deutschland. sascha.staender@gmx.de. · Hautarztpraxis Dr. Michael Ständer, Leutkirch im Allgäu, Deutschland. · Klinik und Poliklinik für Dermatologie und Allergologie der LMU, Frauenlobstraße 9-11, 80337, München, Deutschland. ·Hautarzt · Pubmed #27106503.

ABSTRACT: Psoriasis is a chronic inflammatory disorder of the epidermis, which can be induced by systemic factors, such as streptococci infections or drugs. In addition, psoriasis can be caused by a local cutaneus trauma, known as Koebner phenomenon. Here, we describe a woman with psoriasis in remission, who developed a new psoriatic lesion due to a cutaneous infection with Borrelia burgdorferi. After causal therapy with doxycycline, the erythema migrans and psoriasis lesions disappeared.

25 Article Therapeutic Efficacy of Interleukin 12/Interleukin 23 Blockade in Generalized Pustular Psoriasis Regardless of IL36RN Mutation Status. 2016

Arakawa, Akiko / Ruzicka, Thomas / Prinz, Jörg C. ·Department of Dermatology, University Hospital, Ludwig-Maximilian-University, Munich, Germany. ·JAMA Dermatol · Pubmed #27096382.

ABSTRACT: IMPORTANCE: Generalized pustular psoriasis von Zumbusch type (GPP) is the most severe manifestation of psoriasis. The etiology of GPP is only partially understood, and GPP lacks approved treatments. Loss-of-function mutations in the interleukin 36 (IL-36) receptor antagonist (IL36RN), an inhibitor of innate immune activation in the skin, and therapeutic efficacy of IL-1 blockade in a subset of patients with GPP are viewed as evidence for an autoinflammatory pathogenesis. A pathogenic role of T cells has not been considered. OBJECTIVE: To test whether ustekinumab, a monoclonal antibody blocking IL-12 and IL-23, is an effective treatment modality for patients in whom GPP treatment with conventional psoriasis drugs or antagonists of tumor necrosis factor (TNF) has not been sufficiently effective, is contraindicated, or has lost efficacy. DESIGN, SETTING, AND PARTICIPANTS: We treated a series of 4 patients with GPP with ustekinumab, which was applied on an outpatient basis according to the dosing regimen approved for psoriasis vulgaris. In 3 patients it was combined with low doses of the retinoid acitretin. IL36RN mutations were determined in all 4 patients by means of targeted sequencing of genomic DNA. MAIN OUTCOME MEASURES: The response to therapy was assessed by clinical examination. RESULTS: The 4 patients were female. Sequencing of IL36RN identified a homozygous mutation in case 1 (Pro76Leu). The other 3 patients carried no rare IL36RN variants. Overall GPP duration ranged from 50 to 146 months. Ustekinumab treatment is currently ongoing in all 4 patients without loss of efficacy, currently reaching treatment durations of 17 (case 1) to 44 months (case 3). Ustekinumab treatment induced sustained remissions in all 4 GPP patients. This response was independent of IL36RN mutations and consolidated by combination with low doses of the retinoid acitretin. CONCLUSIONS AND RELEVANCE: Ustekinumab-induced remissions suggest that T cells play a crucial role in GPP pathogenesis based on the documented role that IL-12 and IL-23 play in autoimmune diseases through differentiating helper T cell 1 (TH1) and maintaining TH17 responses. Acitretin treatment may support ustekinumab efficacy, possibly by suppressing TH17 responses through the retinoid-related orphan receptors, RORγt and RORα. Combining IL-12/IL-23 blockade and acitretin may constitute an efficient treatment modality interfering with GPP pathomechanisms.

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