Ricardo Niklas Werner

European S3-Guidelines on the systemic treatment of psoriasis vulgaris - Update 2015 - Short version - EDF in cooperation with EADV and IPC

European S3-Guidelines on the systemic treatment of psoriasis vulgaris – Update 2015 – Short version – EDF in cooperation with EADV and IPC A. Nast,* P. Gisondi, A.D. Ormerod, P. Saiag, C. Smith, P.I. Spuls, P. Arenberger, H. Bachelez, J. Barker, E. Dauden, E.M. de Jong, E. Feist, A. Jacobs, R. Jobling, L. Kem eny, M. Maccarone, U. Mrowietz, K.A. Papp, C. Paul, K. Reich, S. Rosumeck, T. Talme, H.B. Thio, P. van de Kerkhof, R.N. Werner, N. Yawalkar Division of Evidence Based Medicine, Department of Dermatology, Charit e – Universit€ atsmedizin Berlin, Berlin, Germany Section of Dermatology and Venereology, Department of Medicine, University of Verona, Verona, Italy Department of Dermatology, Aberdeen Royal Infirmary, Aberdeen, UK Service de Dermatologie, Hôpital Ambroise Par e Universit e Paris V, Boulogne, France Clinical Lead for Dermatology, St Johns Institute of Dermatology, St Thomas’ Hospital, London, UK Department of Dermatology, Academic Medical Center, Amsterdam, The Netherlands Third Faculty of Medicine, Department of Dermatology, Charles University, Prague, Czech Republic Department of Dermatology, Hôpital Saint-Louis, Paris, France St. Johns Institute of Dermatology, St. Thomas’ Hospital, London, UK Hospital Universitario de la Princesa, Madrid, Spain University Medical Center Nijmegen St Radboud, Nijmegen, The Netherlands Medizinische Klinik mit Schwerpunkt Rheumatologie u. klinische Immonologie, Charit e – Universit€atsmedizin Berlin, Berlin, Germany Cambridge, UK SZTE Borgyogyaszati Klinika, Szeged, Hungary Roma, Italy Department of Dermatology, Psoriasis-Center University Medical Center Schleswig Holstein, Kiel, Germany Waterloo, Canada Department of Dermatology, Paul Sabatier University, Toulouse, France Dermatologikum Hamburg, Hamburg, Germany Section of Dermatology and Venereology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden Department of Dermatology, Erasmus University, Rotterdam, The Netherlands Department of Dermatology, University Hospital Nijmegen, Nijmegen, The Netherlands Department of Dermatology, Inselspital, Universit€ atsklinik f€ ur Dermatologie, Bern, Switzerland *Correspondence: A. Nast. E-mail: alexander.nast@charite.de Received: 22 June 2015; Accepted: 7 July 2015

The natural history of actinic keratosis: a systematic review

Knowledge about the development of untreated actinic keratosis (AK) and risk of progression into squamous cell carcinoma (SCC) is important. Therefore, we set out to synthesize primary data on the natural history of AK. We carried out a systematic literature search (Medline, Medline in Process, Embase, Cochrane) of studies on the natural course of AK, regarding (i) progression and regression rates per lesion‐year, (ii) changes in total lesion counts over time, and (iii) spontaneous field regression and recurrence rates, taking into account studies on participants without immunosuppression and history of skin cancer, immunosuppressed patients and participants with a history of skin cancer and sunscreen use. Twenty‐four eligible studies were identified providing data on at least one of the outcomes. Progression rates of AK to SCC ranged from 0% to 0·075% per lesion‐year, with a risk of up to 0·53% per lesion in patients with prior history of nonmelanoma skin cancer. Rates of regression of single lesions ranged between 15% and 63% after 1 year. The data available on recurrence rates of single lesions 1 year after regression indicate a recurrence rate of 15–53%. Data on the relative change of total AK count over time are heterogeneous, and range from −53% to +99·1%. Spontaneous complete field regression rates range from 0% to 21%, with recurrences in 57%. In general, the available data are limited. Important methodological limitations apply. Currently, no reliable estimates concerning the frequency of AK developing into invasive carcinoma can be given, and further studies are needed.

Evidence- and consensus-based (S3) Guidelines for the Treatment of Actinic Keratosis - International League of Dermatological Societies in cooperation with the European Dermatology Forum - Short version

Actinic keratosis (AK) is a frequent health condition attributable to chronic exposure to ultraviolet radiation. Several treatment options are available and evidence based guidelines are missing.

Efficacy and Safety of Systemic Long-Term Treatments for Moderate-to-Severe Psoriasis: A Systematic Review and Meta-Analysis

Psoriasis as a chronic inflammatory disease often requires effective long-term treatment; a comprehensive systematic evaluation of efficacy and safety of systemic long-term treatments in patients with moderate-to-severe psoriasis is lacking. Twenty-five randomized clinical trials were included. Results were pooled and quality of evidence was assessed using GRADE (Grading of Recommendations Assessment, Development and Evaluation). With respect to PASI 75 (psoriasis area and severity index), pooled risk ratios for infliximab (13.07, 95% confidence interval (CI): 8.60-19.87), secukinumab (11.97, 95% CI: 8.83-16.23), ustekinumab (11.39, 95% CI: 8.94-14.51), adalimumab (8.92, 95% CI: 6.33-12.57), etanercept (8.39, 95% CI: 6.74-10.45), and apremilast (5.83, 95% CI: 2.58-13.17) show superiority of biologics and apremilast in long-term therapy compared with placebo. With respect to the addressed safety parameters, no differences were seen between adalimumab, etanercept, or infliximab versus placebo. No placebo-controlled data on conventional treatments was identified. Head-to-head studies showed superior efficacy of secukinumab and infliximab versus etanercept and of infliximab versus methotrexate. A clear ranking is limited by the lack of long-term head-to-head trials. From the available evidence, infliximab, secukinumab, and ustekinumab are the most efficacious long-term treatments. Data on conventionals are insufficient. Further head-to-head comparisons and studies on safety and patient-related outcomes are needed to draw more reliable conclusions.

Which Antipsoriatic Drug Has the Fastest Onset of Action?—Systematic Review on the Rapidity of the Onset of Action

The time necessary for a treatment to become effective is crucial for patients and physicians but has been largely neglected in the reporting and comparison of clinical trials in dermatology. The aim of this systematic review is to determine the time until the onset of action (TOA) of systemic agents approved for moderate-to-severe psoriasis. Primary outcome is the TOA defined as the weighted mean time until 25% of the patients achieved a psoriasis area and severity index (PASI) 75 response. Among the biologics, infliximab has the shortest TOA (3.5 weeks), followed by ustekinumab (high dose 4.6/low dose 5.1 weeks/not weight adapted), adalimumab (4.6 weeks), etanercept (high dose 6.6/low dose 9.5 weeks), and alefacept (high dose 15.4 weeks/low dose: no data). Among the conventional treatments, good data are available for cyclosporine A (CsA; TOA: 6.0 weeks) and limited data are found for methotrexate (MTX; TOA: high dose 3.2/low dose 9.9 weeks). No data are available for fumaric acid esters and retinoids. This systematic review provides clinically relevant information on the onset of action of antipsoriatic agents, although the data currently available allow only a limited assessment. Psoriasis trials should consider including TOA as an additional outcome measure.

European evidence-based (S3) guideline for the treatment of acne - update 2016 - short version.

European evidence-based (S3) guideline for the treatment of acne – update 2016 – short version A. Nast,* B. Dr eno, V. Bettoli, Z. Bukvic Mokos, K. Degitz, C. Dressler, A.Y. Finlay, M. Haedersdal, J. Lambert, A. Layton, H.B. Lomholt, J.L. L opez-Estebaranz, F. Ochsendorf, C. Oprica, S. Rosumeck, T. Simonart, R.N. Werner, H. Gollnick Division of Evidence-Based Medicine, Klinik f€ ur Dermatologie, Charit e Universit€atsmedizin Berlin, Berlin, Germany Department of Dermatocancerolgy, Nantes University Hospital, Hôtel-Dieu, Nantes, France 3 Department of Clinical and Experimental Medicine, Section of Dermatology, University of Ferrara, Ferrara, Italy Department of Dermatology, School of Medicine University of Zagreb, Zagreb, Croatia 5 Private practice, Munich, Germany Department of Dermatology and Wound Healing, Cardiff University School of Medicine, Cardiff, UK Department of Dermatology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark University Hospital of Antwerp, University of Antwerp, Antwerp, Belgium Department of Dermatology, Harrogate and District Foundation Trust, Harrogate, North Yorkshire, UK Aarhus Universitet, Aarhus, Denmark Dermatology Department, Alcorcon University Hospital Foundation, Alcorc on, Madrid, Spain Department of Dermatology and Venereology, University of Frankfurt, Frankfurt, Germany Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge and Diagnostiskt Centrum Hud, Stockholm, Sweden Private practice, Anderlecht, Belgium Department of Dermatology and Venereology, University of Magdeburg, Magdeburg, Germany *Correspondence: A. Nast. E-mail: alexander.nast@charite.de

European consensus-based (S2k) Guideline on the Management of Herpes Zoster – guided by the European Dermatology Forum (EDF) in cooperation with the European Academy of Dermatology and Venereology (EADV), Part 2: Treatment

Herpes zoster (HZ, shingles) is a frequent medical condition which may severely impact the quality of life of affected patients. Different therapeutic approaches to treat acute HZ are available. The aim of this European project was the elaboration of a consensus‐based guideline on the management of patients who present with HZ, considering different patient populations and different localizations. This interdisciplinary guideline aims at an improvement of the outcomes of the acute HZ management concerning disease duration, acute pain and quality of life of the affected patients and at a reduction in the incidence of postherpetic neuralgia (PHN) and other complications. The guideline development followed a structured and pre‐defined process, considering the quality criteria for guidelines development as suggested by the AGREE II instrument. The steering group was responsible for the planning and the organization of the guideline development process (Division of Evidence‐Based Medicine, dEBM). The expert panel was nominated by virtue of clinical expertise and/or scientific experience and included experts from the fields of dermatology, virology/infectiology, ophthalmology, otolaryngology, neurology and anaesthesiology. Recommendations for clinical practice were formally consented during the consensus conference, explicitly considering different relevant aspects. The guideline was approved by the commissioning societies after an extensive internal and external review process. In this second part of the guideline, therapeutic interventions have been evaluated. The expert panel formally consented recommendations for the treatment of patients with HZ (antiviral medication, pain management, local therapy), considering various clinical situations. Users of the guideline must carefully check whether the recommendations are appropriate for the context of intended application. In the setting of an international guideline, it is generally important to consider different national approaches and legal circumstances with regard to the regulatory approval, availability and reimbursement of diagnostic and therapeutic interventions.

Report from the kick-off meeting of the Cochrane Skin Group Core Outcome Set Initiative (CSG-COUSIN).

A major obstacle of evidence‐based clinical decision making is the use of nonstandardized, partly untested outcome measurement instruments. Core Outcome Sets (COSs) are currently developed in different medical fields to standardize and improve the selection of outcomes and outcome measurement instruments in clinical trials, in order to pool results of trials or to allow indirect comparison between interventions. A COS is an agreed minimum set of outcomes that should be measured and reported in all clinical trials of a specific disease or trial population. The international, multidisciplinary Cochrane Skin Group Core Outcome Set Initiative (CSG‐COUSIN) aims to develop and implement COSs in dermatology, thus making trial evidence comparable and, herewith, more useful for clinical decision making. The inaugural meeting of CSG‐COUSIN was held on 17–18 March 2015 in Dresden, Germany, as the exclusive theme of the Annual Cochrane Skin Group Meeting. In total, 29 individuals representing a broad mix of different stakeholder groups, professions, skills and perspectives attended. This report provides a description of existing COS initiatives in dermatology, highlights current methodological challenges in COS development, and presents the concept, aims and structure of CSG‐COUSIN.

Methods and Results Report – Evidence and consensus-based (S3) Guidelines for the Treatment of Actinic Keratosis –International League of Dermatological Societies in cooperation with the European Dermatology Forum

Methods and Results Report – Evidence and consensusbased (S3) Guidelines for the Treatment of Actinic Keratosis – International League of Dermatological Societies in cooperation with the European Dermatology Forum R.N. Werner, A. Jacobs, S. Rosumeck, R. Erdmann, B. Sporbeck, A. Nast Division of Evidence Based Medicine (dEBM), Department of Dermatology, Venerology and Allergology, Charit e – Universit€atsmedizin Berlin, Berlin, Germany Received: 3 March 2015; Accepted: 3 April 2015

Methods Report: European S3‐Guidelines on the systemic treatment of psoriasis vulgaris – update 2015 – EDF in cooperation with EADV and IPC

2.3.3 Literature search: Update search for primary literature 5 2.3.4 Data extraction 5 2.3.5 Data analysis 5 2.3.6 Quality assessment of the evidence 6 2.3.7 Presentation of the results 8 2.4 Special considerations and special patient populations 8 2.5 Development of recommendations/consensus process 8 2.6 Peer review and piloting 8 2.7 Implementation, evaluation, updating 9 3 References 9 4 Appendices 11 4.1 Declarations of Conflicts of interest 11 4.2 Electronic search strategies used for the literature search 21