Summary
Dermatologists may choose from various conventional and biological systemic agents to treat patients with moderate‐to‐severe psoriasis. We set out to analyse systematically the efficacy and ...tolerability of approved treatments for moderate‐to‐severe psoriasis. We undertook a systematic review and meta‐analysis of randomized controlled trials (RCTs) investigating the efficacy of systemic treatment approved for moderate‐to‐severe psoriasis. Efficacy was assessed as the proportion of participants with 75% improvement in Psoriasis Area and Severity Index at primary efficacy measurement (week 8–16). Safety was summarized as rates of adverse events and withdrawals. Direct and indirect comparative efficacy was assessed by random effects meta‐analysis of risk differences (RDs). In total, 48 eligible RCTs totalling 16 696 patients (11 178 randomized to biologics, 1888 to conventional treatments) were identified. In placebo‐controlled trials, infliximab was the most efficacious RD 76%, 95% confidence interval (CI) 73–79%. Adalimumab (RD 61%, 95% CI 56–67%), and ustekinumab 45 mg (RD 63%, 95% CI 59–66%) and 90 mg (RD 67%, 95% CI 60–74%) each had similar efficacy. These biologics are more effective than etanercept and all conventional treatments. Head‐to‐head trials indicate the superiority of adalimumab and infliximab over methotrexate (MTX), the superiority of ustekinumab over etanercept, the nonsignificant superiority of ciclosporin over MTX, and the dose‐dependent efficacy of etanercept and ustekinumab. Fumaric acid is as efficacious as MTX. Safety of treatments could not be pooled due to a lack of standardization in reporting across trials. In conclusion, the qualitative and quantitative evidence is much stronger for biological interventions than for conventional treatments.
What's already known about this topic?
Direct comparisons of the different treatment options available for psoriasis are scarce, and most studies were done on a verum vs. placebo basis.
Safety data have been reported in most trials, but systematic summaries of the safety data for patients with psoriasis are scarce.
In previous reviews, biological treatments did not appear to be generally superior to conventional systemic treatments.
What does this study add?
This review identifies infliximab, adalimumab and ustekinumab as the most efficacious treatments during induction therapy.
Some additional evidence has been generated for the conventional systemic antipsoriatics, but evidence remains better for biologics.
Due to the heterogeneity in study reporting, a direct or indirect comparison of safety data is very difficult to achieve, and there is a strong need to standardize safety reporting in psoriasis trials.
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.
Background
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.
Objectives
The goal of these evidence‐ and consensus‐based guidelines was the development of treatment recommendations appropriate for different subgroups of patients presenting with AK. A secondary aim of these guidelines was the implementation of knowledge relating to the clinical background of AK, including consensus‐based recommendations for the histopathological definition, diagnosis and the assessment of patients.
Methods
The guidelines development followed a pre‐defined and structured process. For the underlying systematic literature review of interventions for AK, the methodology suggested by the Cochrane Handbook for Systematic Reviews of Interventions, the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) statement and Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was adapted. All recommendations were consented during a consensus conference using a formal consensus methodology. Strength of recommendations was expressed based on the GRADE approach. If expert opinion without external evidence was incorporated into the reasoning for making a certain recommendation, the rationale was provided. The Guidelines underwent open public review and approval by the commissioning societies.
Results
Various interventions for the treatment of AK have been assessed for their efficacy. The consenting procedure led to a treatment algorithm as shown in the guidelines document. Based on expert consensus, the present guidelines present recommendations on the classification of patients, diagnosis and histopathological definition of AK. Details on the methods and results of the systematic literature review and guideline development process have been published separately.
Conclusions
International guidelines are intended to be adapted to national or regional circumstances (regulatory approval, availability and reimbursement of treatments).
Summary
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.
What's already known about this topic?
Psoriasis is a chronic disease, and for many patients a maintenance treatment is highly relevant.
Good data and reviews are available on efficacy during the induction period.
There is a lack of systematic reviews on the efficacy of maintenance treatments once the patients have become a responder during the induction period.
What does this study add?
Compared with placebo, ciclosporin 5 mg kg−1 twice weekly or 3 mg kg−1 daily is effective in the maintenance phase.
No differences in PASI 75 response were found when adalimumab 40 mg was given every other week or every 4 weeks.
Continuous infliximab treatment is superior to as‐needed treatment.
Data from uncontrolled analyses indicate a maintained PASI 75 response in approximately three‐quarters of patients during long‐term etanercept 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 of the incidence of postherpetic neuralgia and other complications. The guideline development followed a structured and predefined 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 first part of the guideline, diagnostic means have been evaluated. The expert panel formally consented recommendations for the management of patients with (suspected) HZ, referring to the assessment of HZ patients, considering various specific 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.
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