Anja Jacobs

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.

Risk of complications due to anticoagulation during dermatosurgical procedures: a systematic review and meta‐analysis

Background Management of anticoagulation and anti‐platelet drugs during cutaneous surgery is still a challenge for many dermatologists and standards of care with respect to stopping, continuing or bridging vary widely. Methods We performed a systematic review (Medline, Cochrane Library, until August 27th, 2013) of studies assessing the risk of complications due to anticoagulation during cutaneous surgery. Primary outcomes were mild‐moderate and severe postsurgical bleeding. The secondary outcomes were excessive and uncontrollable intraoperative bleeding and other postsurgical complications as wound dehiscence, erythema, wound infection. Results 1.287 publications were identified and 10 studies were included into the review. The frequencies of bleeding in the control groups in general were low (about 1%). In patients on aspirin, increased risks were seen neither with respect to mild‐moderate postoperative bleeding (RR 1.1, CI 0.5–2.3), nor with respect to severe bleeding (RR 0.9, CI 0.2–4.6). The studies with patients on warfarin showed a risk for mild‐moderate bleeding that was three times as high as in controls (RR 3.2, CI 1.4–7.1) and for severe bleeding that was 15 times higher (RR 14.8, CI 2.7–80.4). In general the study sizes were small and the methodological quality low. Conclusion The risk of bleeding due to a medication with aspirin seems to be negligible. With warfarin, the risk is increased; an exact estimate of the risk increase is difficult to give, because of the lack of sufficient high quality studies. A two‐fold increase appears likely, the 15‐fold increase is most likely due to statistical reasons arising from the rareness of the event in the small number of included patients. Stopping, bridging or continuing a medication should always be an individual decision. In accordance with guidelines from internal medicine for most patients it will be recommendable to continue with the medication.

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

Topical treatments for scalp psoriasis - summary of a Cochrane Systematic Review.

People with chronic plaque psoriasis often have lesions on the scalp that are difficult to treat. This report is a summary of a Cochrane review on the efficacy and safety of topical treatments for scalp psoriasis. For quality‐of‐evidence assessment, we used the Grading of Recommendations Assessment, Development and Evaluation Working Group approach. Only randomized controlled trials (RCTs) were eligible for inclusion. We searched the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase and LILACS; ongoing trials; indexes of included studies and screened abstracts of six psoriasis‐specific conferences up to August 2015. We included 59 RCTs, with 11 561 participants overall. Most findings were limited to short‐term treatments (< 6 months). According to the clinician and patients’ self‐assessment, a corticosteroid–vitamin D combination (e.g. betamethasone dipropionate plus calcipotriol) and corticosteroids of high and very high potency were better than vitamin D. The two‐compound combination was superior to the corticosteroid alone, but the additional benefit was small. Reporting of quality‐of‐life data was insufficient. The two‐compound combination and corticosteroids caused fewer withdrawals due to adverse events than vitamin D. There was no difference between the two‐compound combination and corticosteroid monotherapy concerning this outcome. Overall the evidence was of moderate quality. Evaluation of other topical treatments was limited. Given the comparable safety profile and only slim benefit of the two‐compound combination over the corticosteroid alone, monotherapy with generic topical corticosteroids of high and very high potency may be fully acceptable for short‐term therapy. More quality‐of‐life data and long‐term assessments are needed.

Online consensus conferences for clinical guidelines development - a survey among participants from the International Guidelines for the Treatment of Actinic Keratosis.

RATIONALE, AIMS AND OBJECTIVES Guideline development requires considerable time and financial resources. New technical devices such as software for online conferences may help to reduce time and financial efforts of guidelines development. The present survey may serve as an explorative pilot for a future study to determine the technical feasibility, acceptability and possible weaknesses of online consensus conferences for clinical guidelines development. METHODS An anonymous online survey was conducted among participants in the online consensus conference of the International League of Dermatological Societies (ILDS) Guidelines for the Treatment of Actinic Keratosis. RESULTS The majority of participants reported no technical problems with the participation in the online consensus conference; one participant had substantial technical problems accountable to a regional telephone breakdown. The majority of participants would not have preferred a traditional face-to-face conference, and all participants rated online consensus conferences for international guidelines as absolutely acceptable. Rates of acceptance were particularly high among those participants with prior experience with consensus conferences. Certain aspects, particularly the possibilities of debating, were rated as possibly superior in face-to-face conferences by some participants. CONCLUSIONS The data from the online survey indicate that online consensus conferences may be an appropriate alternative to traditional face-to-face consensus conferences, especially within the frame of international guidelines that would require high travel costs and time. Further research is necessary to confirm the data from this explorative pilot study.Rationale, aims and objectives Guideline development requires considerable time and financial resources. New technical devices such as software for online conferences may help to reduce time and financial efforts of guidelines development. The present survey may serve as an explorative pilot for a future study to determine the technical feasibility, acceptability and possible weaknesses of online consensus conferences for clinical guidelines development. Methods An anonymous online survey was conducted among participants in the online consensus conference of the International League of Dermatological Societies (ILDS) Guidelines for the Treatment of Actinic Keratosis. Results The majority of participants reported no technical problems with the participation in the online consensus conference; one participant had substantial technical problems accountable to a regional telephone breakdown. The majority of participants would not have preferred a traditional face-to-face conference, and all participants rated online consensus conferences for international guidelines as absolutely acceptable. Rates of acceptance were particularly high among those participants with prior experience with consensus conferences. Certain aspects, particularly the possibilities of debating, were rated as possibly superior in face-to-face conferences by some participants. Conclusions The data from the online survey indicate that online consensus conferences may be an appropriate alternative to traditional face-to-face consensus conferences, especially within the frame of international guidelines that would require high travel costs and time. Further research is necessary to confirm the data from this explorative pilot study.

Systematic review on the maintenance of response during systemic antipsoriatic therapy

As a chronic disease psoriasis often requires long‐term treatment. Successful continuation of therapy during a maintenance phase is therefore important. A systematic review was performed on the efficacy of psoriasis drugs during maintenance treatment in patients who had achieved sufficient treatment success during the induction period. Maintenance therapy is defined as treatment during the period after successful induction therapy. Inclusion criteria were prospective studies with systemic therapies recommended by the 2009 European psoriasis guidelines (plus ustekinumab), and a study population that had achieved a defined treatment response criterion after induction therapy within a period of ≥ 6 months. Maintenance studies on conventional treatments were identified for ciclosporin (CSA) only (no studies investigating acitretin, methotrexate or ustekinumab were found). Compared with placebo, CSA was shown to be effective in maintenance therapy, yet CSA 1·5 mg kg−1 seems to be insufficient to maintain disease control. Based on the evidence, it is uncertain whether there is any difference between daily or intermittent treatment. For biologics, maintenance data were available for adalimumab, etanercept and infliximab. No differences in 75% improvement in Psoriasis Area and Severity Index (PASI 75) response were identified between adalimumab 40 mg once and twice a month. Continuous infliximab treatment was shown to be superior to as‐needed treatment. For etanercept, only observational postrandomized controlled trial data were available, indicating a maintained PASI 75 response in approximately three‐quarters of patients during long‐term treatment. Only limited evidence is available for a conclusion on how patients with an adequate response should be optimally treated during the maintenance period. A clear ranking of the available treatments is not yet possible.

Methodological standards in medical reporting

Published research findings are the basis for health care decisions or further medical research. However, reporting of research methods and findings is often incomplete and of insufficient quality. Poor reporting hampers the assessment of reliability and validity of study results. Strengths and weaknesses of the investigation cannot be completely evaluated and subsequently it can mislead decision making in health care or in further clinical research.

P092 Does The Addition Of Symbols Make Guidelines Recommendations Clearer? Results From An Online Survey

Background A recent study has shown that the perceived meaning of wordings in recommendations such as “should” or “must” can vary among guideline users. In addition to the wordings, many guidelines use graphic symbols such as arrows or smileys to support their recommendations. Objectives To determine whether such symbols influence the perceived meaning of the recommendations or may help to reduce variation in the perception of the meaning between different guidelines’ users. Methods With the help of an online-survey, using a visual analogue scale (0–100), participating physicians from different specialties were asked to express their perceived levels of obligation when confronted with different guidelines recommendations in combination with different symbols. Results 269 physicians participated, the addition of a “single arrow” or “double arrow” to the recommendation did not lead to relevant changes in the perceived obligation expressed by the recommendation (median: soll/shall: 83 vs. 87; “sollte/should”: 77 vs. 78). In comparison to the prior study, variations in the interpretation of typical guideline wordings were not reduced if symbols were used additionally. Discussion In this study, the impact of symbols on the understanding of a guidelines recommendation was limited. Important methodological limitations apply but this study questions the impact of symbols to clarify a recommendation’s message. However, visual aids are likely to be very important for users to help to identify recommendations within larger text document and therefore make guidelines easier to use and implement.