Currently no treat-to-target framework to guide systemic treatment in adults with moderate-to-severe atopic dermatitis exists. We sought to reach international consensus through an eDelphi process on ...a core set of recommendations for such an approach. Recommendations were developed by an international Steering Committee, spanning 3 areas (Guiding Principles, Decision Making, and Outcome Thresholds) and 2 specific time-points; an initial acceptable target at 3 months and an optimal target at 6 months, each based on improvements in patient global assessment plus at least one specific outcome domain. These treat-to-target- orientated recommendations were evaluated by an extended international panel of physicians, nurses and patients. Proposed recommendations were rated using a 9-point Likert scale; for each recommendation, consensus agreement was reached if ≥ 75% of all respondents rated agreement as ≥ 7. Consensus on 16 core recommendations was reached over 2 eDelphi rounds. These provide a framework for shared decision-making on systemic treatment continuation, modification, or discontinuation.
Summary
Background
Daylight photodynamic therapy (DL‐PDT) of actinic keratosis (AK) has shown preliminary efficacy and safety results comparable to conventional photodynamic therapy (c‐PDT), using ...methyl aminolevulinate (MAL) cream.
Objectives
To demonstrate the efficacy and safety of DL‐PDT vs. c‐PDT in treating mild facial/scalp AK.
Materials and methods
This 24‐week randomized, controlled, investigator‐blinded, multicentre, intra‐individual efficacy (non‐inferiority) and safety (superiority regarding pain) study enrolled 100 subjects. AKs on the face/scalp were treated once, with DL‐PDT on one side and c‐PDT on the contralateral side. Primary end points for DL‐PDT at week 12 were efficacy non‐inferiority regarding complete lesion response (mild AK) and safety (superiority regarding subject's assessment of pain). Lesions with complete response 12 weeks after one treatment session were followed until week 24. The safety evaluation included incidence of adverse events. Subject satisfaction was classified using a questionnaire.
Results
At week 12, the complete lesion response rate with DL‐PDT was non‐inferior to c‐PDT (89·2% vs. 92·8%, respectively; 95% confidence interval −6·8 to −0·3), confirmed by intention‐to‐treat analysis. Additionally, regardless of the treatment used, 96% of mild lesions were maintained in complete response 24 weeks after the PDT session. For DL‐PDT, subject‐reported pain was significantly lower (0·8 vs. 5·7, respectively; P < 0·001), with better tolerability and significantly higher subject satisfaction regarding convenience and outcome.
Conclusions
Daylight‐mediated PDT was not inferior in efficacy to Metvix c‐PDT (mild AK response rate), better tolerated, nearly painless and more convenient for patients.
What's already known about this topic?
Methyl aminolevulinate conventional photodynamic therapy (MAL c‐PDT) is effective for treating actinic keratosis (AK), but may be a painful, inconvenient procedure. Daylight PDT (DL‐PDT) has shown good efficacy and safety results compared with c‐PDT in a previous randomized, controlled, exploratory trial.
What does this study add?
This study confirms previous findings that DL‐PDT can be considered as an effective, safe and convenient alternative for the treatment of facial/scalp AK.
This is the first study showing a high maintenance of complete lesion response 6 months after one treatment.
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
Background Efalizumab (anti‐CD11a), a humanized monoclonal antibody, blocks multiple T‐cell‐dependent functions implicated in the pathogenesis of psoriasis, including T‐cell activation, ...migration to the skin, reactivation in psoriatic skin and interactions with keratinocytes.
Objectives This multinational, randomized, double‐blind, placebo‐controlled, parallel‐group trial was designed to evaluate the safety and efficacy of subcutaneous efalizumab 1·0 mg kg−1 once weekly for 12 weeks compared with placebo in a population that included high‐need patients, defined as those for whom at least two systemic therapies were unsuitable because of lack of efficacy, intolerance or contraindication.
Patients/methods Patients with moderate‐to‐severe plaque psoriasis involvement of ≥ 10% of total body surface area and Psoriasis Area and Severity Index (PASI) ≥ 12·0 at screening were randomized in a 2 : 1 ratio to receive efalizumab or placebo. The primary efficacy endpoint was the proportion of patients achieving ≥ 75% PASI improvement (PASI‐75 response) at week 12 in the intention‐to‐treat population; secondary endpoints included changes in PASI, static Physician's Global Assessment, Physician's Global Assessment of change from baseline and percentage of body surface area affected.
Results We enrolled 793 patients (529 received efalizumab and 264 placebo), including 526 high‐need patients (342 received efalizumab and 184 placebo). Week 12 PASI‐75 rates were 29·5% for efalizumab compared with 2·7% for placebo among high‐need patients (P < 0·0001) and 31·4% for efalizumab compared with 4·2% for placebo in the full study population (P < 0·0001). Results for all secondary efficacy endpoints showed superiority of efalizumab over placebo in both the high‐need and the full populations. Efalizumab demonstrated a favourable safety profile, without evidence of systemic toxicity, in both the high‐need group and the overall study population.
Conclusions The efficacy and safety of efalizumab therapy were comparable between high‐need patients and the more general moderate‐to‐severe psoriasis patient population. In view of its demonstrated efficacy and safety profile, efalizumab represents a valuable option for the treatment of adult patients with moderate‐to‐severe plaque psoriasis, including high‐need patients.
Summary
Background Clinical studies in cutaneous conditions other than actinic keratosis (AK) have revealed that the safety and efficacy profile of imiquimod is influenced by dosing frequency.
...Objectives To evaluate dosing frequency response of imiquimod 5% for treatment of AK.
Methods This was a phase II, multicentre, randomized, double‐blind, placebo‐controlled study. Adults with ≥ 10 but ≤ 50 clinical AKs, one of which was histologically confirmed, were randomized (4 : 1) to 2–6 packets of imiquimod or placebo cream applied to the dorsum of the forearms and hands once daily 2, 3, 5 or 7 times per week for 8 weeks. The primary endpoint was complete clearance of AKs in the treatment area at 8 weeks post‐treatment.
Results One hundred and forty‐nine (94 men and 54 women) white subjects, with a mean ± SD age of 71 ± 10·2 years, were enrolled. Twenty‐eight subjects (18·8%) discontinued from study: 0%, 3·1%, 6·9%, 30·0% and 33·3% withdrew for local skin reactions or adverse events in the combined placebo, and in the imiquimod 2, 3, 5 or 7 times per week groups, respectively. Seven serious adverse events occurred; none was related to the study drug. Median baseline lesions ranged from 38 to 40 for the treatment groups. Complete clearance was achieved in 0%, 3·2%, 6·9%, 3·3% and 6·7% of subjects, and partial clearance (≥ 75% lesion reduction) in 0%, 22·6%, 24·1%, 20·0% and 36·7% of subjects for the placebo and imiquimod 2, 3, 5 or 7 times per week regimens, respectively.
Conclusions Imiquimod 5% applied more frequently than 3 times per week to AKs was not well tolerated. Complete clearance rates were low; however, partial clearance rates increased with increased dosing frequency (P = 0·002).
Summary
Background The increased incidence of skin cancers after solid organ transplantation is well recognized. Skin cancers developing in transplant recipients are more aggressive in behaviour. ...Therapeutic options to reduce and/or delay the development of cutaneous neoplasms are therefore of interest.
Objectives The objective of this review was to summarize the available medical literature from randomized controlled trials on the use of oral retinoids as a preventive agent for skin cancers in the solid organ transplant population.
Methods Three electronic databases were searched for relevant trials: MEDLINE (1966–October 2003), EMBASE (1980–week 44, 2003) and the Cochrane Controlled Trials Register (third quarter 2003). Randomized or quasi‐randomized controlled clinical trials on subjects of any age or ethnic background who had received a solid organ transplant (cardiac, renal, liver, etc.) were evaluated. All titles and s found by the search strategy were independently reviewed by two researchers for inclusion into the review.
Results Eighty‐one s were identified through the electronic databases for consideration. Review of the s identified three eligible trials. One cross‐over trial involving 23 subjects treated with acitretin 25 mg daily for 12 months reported 46 squamous cell carcinomas (SCCs) developing in six subjects during acitretin treatment vs. 65 SCCs developing in 15 subjects during the drug‐free period. Another trial involving 44 subjects treated with acitretin 30 mg daily or placebo for 6 months reported two of 19 subjects developing two SCCs in the treatment group vs. nine of 19 subjects developing 18 new skin cancers (15 SCCs, one Bowen's disease, two basal cell carcinomas) in the placebo group. One dose comparison trial involving 26 renal transplant recipients treated with acitretin did not find a significant difference in numbers of skin cancers developing at the doses examined. The major limitation to the use of acitretin was poor tolerance due to adverse events. Headaches, rash, musculoskeletal symptoms and hyperlipidaemia were the most common causes of withdrawal from treatment. No alterations in renal or liver function were detected during the periods of treatment or follow‐up.
Conclusions The available data from a small number of randomized controlled trials suggest that acitretin may have a role in the management of solid organ transplant recipients with skin cancers. Tolerability of the drug is a major factor limiting its use. Appropriate selection of patients may help improve the risk–benefit ratio.
Summary
Basal cell carcinoma is the most common malignancy among caucasians worldwide. Accurate epidemiological data can be difficult to obtain, but does suggest that the overall incidence is ...increasing. Risk factors include skin type, prior skin cancers and immunosuppression. Research in free radical‐mediated cellular injury and innate defence mechanisms, and ultraviolet radiation‐induced genetic mutations have improved our understanding of the development of this disorder.
Summary
Imiquimod is being investigated as a therapeutic option for the management of actinic keratosis. Three recent clinical trials have demonstrated a reasonable efficacy rate and high safety ...profile. ‘Cycle’ therapy may improve the safety profile while maintaining efficacy. ‘Field’ treatment with imiquimod may uncover and treat ‘subclinical’ actinic keratoses, which in turn may potentially result in fewer recurrences. Longer follow‐up studies are required to investigate this possibility.
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