Summary
Aim
There are numerous systemic medications in use for psoriasis, with additional investigational agents being studied. However, head‐to‐head, randomized clinical trials are rare and cannot ...feasibly compare all treatments. A network meta‐analysis (NMA) synthesizes the available evidence to provide estimates for all pairwise comparisons. Here, we summarize and appraise two recent NMAs that assessed systemic therapies for moderate‐to‐severe psoriasis.
Setting and design
Two systematic reviews searched databases and the grey literature to identify relevant randomized clinical trials.
Study participants
The reviews mostly included trials that involved adults with moderate‐to‐severe psoriasis. One of the reviews also included two trials involving children.
Study exposure
Interventions common to both reviews include adalimumab, etanercept, infliximab, ustekinumab, ixekizumab, secukinumab and methotrexate. One of the reviews included additional interventions, primarily other biological agents along with new small‐molecule treatments and systemic conventional treatments.
Primary outcomes
One review focused on ‘clear/nearly clear’ and withdrawals from adverse events as study outcomes, while the second review focused on improvement of ≥ 90% measured on the Psoriasis Area and Severity Index (PASI 90) and serious adverse events.
Outcomes
Additional outcomes included quality of life, PASI 75, Physician's Global Assessment of 0/1 and any adverse event.
Results
Overall, both NMAs are of high quality and provide a comprehensive summary of the evidence base and treatment effects. Results, in terms of both estimates and rankings, suggest that newer biologics targeting the interleukin (IL)‐12/23 and IL‐17 axes appear to be more effective than older biologics and oral agents.
Conclusions
Patients, clinicians and policy makers can use the relative efficacy assessments of NMAs to inform decision making regarding the clearance of psoriasis skin lesions at relevant time points and improvement in quality of life.
Summary
Background
Quality of life (QoL) is one of the core outcome domains identified by the Harmonising Outcome Measures for Eczema (HOME) initiative to be assessed in every eczema trial. There is ...uncertainty about the most appropriate QoL instrument to measure this domain in infants, children and adolescents.
Objectives
To systematically evaluate the measurement properties of existing measurement instruments developed and/or validated for the measurement of QoL in infants, children and adolescents with eczema.
Methods
A systematic literature search in PubMed and Embase, complemented by a thorough hand search of reference lists, retrieved studies on measurement properties of eczema QoL instruments for infants, children and adolescents. For all eligible studies, we judged the adequacy of the measurement properties and the methodological study quality with the COnsensus‐based Standards for the selection of health Measurement INstruments (COSMIN) checklist. Results from different studies were summarized in a best‐evidence synthesis and formed the basis to assign four degrees of recommendation.
Results
Seventeen articles, three of which were found by hand search, were included. These 17 articles reported on 24 instruments. No instrument can be recommended for use in all eczema trials because none fulfilled all required adequacy criteria. With adequate internal consistency, reliability and hypothesis testing, the U.S. version of the Childhood Atopic Dermatitis Impact Scale (CADIS), a proxy‐reported instrument, has the potential to be recommended depending on the results of further validation studies. All other instruments, including all self‐reported ones, lacked significant validation data.
Conclusions
Currently, no QoL instrument for infants, children and adolescents with eczema can be highly recommended. Future validation research should primarily focus on the CADIS, but also attempt to broaden the evidence base for the validity of self‐reported instruments.
What's already known about this topic?
Most eczema trials include the Infants’ Dermatitis Quality of Life Index (IDQoL) or the Children's Dermatology Life Quality Index (CDLQI) as quality of life (QoL) measurement instruments.
It is unclear which instruments are most appropriate to measure QoL in infants, children and adolescents with eczema.
What does this study add?
Most QoL instruments for infants, children and adolescents with eczema are poorly validated, indicating a clear need for further validation work.
Linked Comment: Chu. Br J Dermatol 2017; 176:848–849
Summary
Background Filaggrin loss‐of‐function (FLG) mutations are associated with eczema and skin barrier impairment, but it is unclear whether skin barrier impairment precedes phenotypic eczema in ...FLG mutation carriers.
Objectives To study the association between FLG mutations, skin barrier impairment and clinical eczema at 3 months of age.
Methods A total of 88 infants were examined for eczema. Disease severity was determined by the SCORAD eczema severity score. Transepidermal water loss (TEWL) was measured on unaffected forearm skin. Venous blood samples were screened for the four most common FLG mutations found in the U.K. white population (R501X, 2282del4, R2447X and S3247X). Median SCORAD and TEWL measurements in children with and without eczema and FLG mutations were compared.
Results Thirty‐three per cent (29/88) of children had clinical eczema. Median SCORAD was 10·6 (range 3·5–31·0). TEWL (g m−2 h−1) was higher in children with eczema compared with unaffected infants (median TEWL 14·24 vs. 11·24, P < 0·001). Higher TEWL was associated with more severe disease (r = 0·59, P < 0·001, median TEWL, SCORAD < 15, 13·1 vs. 29·6, SCORAD ≥ 15, P = 0·029). Clinically dry skin was associated with higher TEWL, even in the absence of eczema (median TEWL 17·55 vs. 11·08, P = 0·008). Seventeen per cent (15/88) of children carried at least one FLG mutation. FLG mutation carriers were significantly more likely to have clinically dry skin, even in the absence of eczema odds ratio (OR) 8·50, 95% confidence interval (CI) 1·09–66·58, P = 0·042. FLG mutation carriers were also more likely to have eczema by 3 months of age (OR 4·26, 95% CI 1·34–13·57, P = 0·014). FLG mutations were significantly associated with higher median TEWL (all children, FLG‘yes’ 21·59 vs. FLG‘no’ 11·24, P < 0·001), even without clinical eczema (FLG‘yes’ 15·99 vs. FLG‘no’ 10·82, P = 0·01).
Conclusions By the age of 3 months, FLG mutations are associated with an eczema phenotype, dry skin and TEWL. The observation that TEWL is elevated in unaffected FLG mutation carriers suggests that skin barrier impairment precedes clinical eczema.
Summary
Lichen sclerosus is one of the dermatoses that specifically affects the anogenital skin. It has peaks of incidence in prepubertal girls and postmenopausal women. The objective of this ...critical appraisal was to review systematically the evidence for efficacy and safety of different treatments. There are no randomized controlled studies of treatment in prepubertal girls and most studies are small case series or case reports. There is little focus on quality of life.
What's already known about this topic?
Lichen sclerosus occurs in prepubertal girls.
Topical steroids are commonly used in both children and adults with good effect.
Small series report benefit with calcineurin inhibitors.
What does this study add?
The use of topical clobetasol propionate 0.05% is an effective and safe treatment for lichen sclerosus in prepubertal girls.
Summary
Background
For many years dermatologists have had access to few therapies for patients with moderate‐to‐severe atopic eczema (AE). New promising therapies are entering the market but ...conventional phototherapies and systemic therapies have more well‐known safety profiles, lower costs and wider availability.
Objectives
To provide insight into current prescribing practices of conventional phototherapy and systemic immunomodulatory therapies for adults with chronic AE, and the factors influencing these prescribing practices, before biologics and other novel therapeutics become routine clinical practice.
Methods
In this exploratory study dermatologists were invited to participate in an online survey via a mailing list of the European Academy of Dermatology and Venereology and national societies. Data were collected on participant characteristics (including clinical practice data), the use of phototherapies and systemic therapies, and factors influencing their use.
Results
From 30 European countries, 238 out of 361 dermatologists willing to participate (65·9%) completed the survey, with 229 meeting the inclusion criteria. For phototherapy (prescribed by 84·7%), most preferred narrowband ultraviolet B as first line (80·9%) and psoralen plus ultraviolet A as second (21·6%). For systemic therapy (prescribed by 95·2%) ciclosporin (54·1%), oral corticosteroids (32·6%) and methotrexate (30·7%) were used first line. Dermatologists relied mostly on personal experience for prescribing phototherapy and systemic therapy. Azathioprine and mycophenolic acid were prescribed by only 135 (59·0%) and 85 (37·1%) participants in total, mostly due to a lack of personal experience.
Conclusions
This study provides insight into prescribing practices for conventional phototherapy and systemic therapy in Europe and shows that off‐label therapies are also preferred as first‐line choice of systemic therapy.
What is already known about this topic?
Varying prescribing practices were found for adult (in the UK) and paediatric (in Northern America and Europe) patients with moderate‐to-severe atopic eczema (AE).
Not much is known about the prescription of phototherapy and (off‐label) systemic therapy for adult patients in Europe.
Although therapies like dupilumab are promising new treatment modalities, better‐known safety profiles, lower costs and better availability are reasons to improve the evidence profile of conventional systemic therapies like ciclosporin.
What does this study add?
Prescribing practices of European dermatologists treating adult patients with moderate‐to-severe AE show diversity.
Most dermatologists prefer narrowband ultraviolet B as first‐line phototherapy, followed by psoralen plus ultraviolet A as second line.
Next to ciclosporin, which is most commonly prescribed, (off‐label) methotrexate and oral corticosteroids are also frequently used as first‐line systemic agents in chronic AE.
Lack of personal experience with azathioprine and mycophenolic acid was the most important reason against their prescription.
What are the clinical implications of the work?
The results from this study might help to improve the experience with, and prescribing of, all available conventional phototherapies and (off‐label) systemic therapies.
Guidelines developers might use these results to develop and implement treatment algorithms.
Linked Comment: Bruin‐Weller. Br J Dermatol 2020; 183:987–988.
Plain language summary available online
Summary
Aim
El‐Khalawany et al. (Eur J Pediatr 2012; 172: 351–6) aimed to compare the efficacy and safety of methotrexate vs. ciclosporin in the treatment of children with severe atopic eczema.
...Setting and design
This multicentre, parallel group (ratio 1 : 1), randomized controlled trial was conducted in a secondary care setting in Egypt.
Study exposure
Children with severe atopic eczema were randomly assigned to receive either methotrexate (7·5 mg weekly) or ciclosporin (2·5 mg kg−1 daily) for 12 weeks, followed by a 12‐week follow‐up period.
Outcomes
Eczema severity was measured using the SCORing of Atopic Dermatitis (SCORAD) index. The authors also recorded the number of patients on each therapy experiencing adverse effects.
Primary outcome measures
The primary outcome was the mean change in SCORAD after 12 weeks of treatment.
Results
Forty patients with a mean age of 11·6 ± 1·52 years were included in the trial. At week 12, patients in the methotrexate group had a mean ± SD absolute reduction in SCORAD of 26·25 ± 7·03, compared with 25·02 ± 8·21 in the ciclosporin group (P = 0·93). Both drugs were associated with minor adverse effects, none of which necessitated changing the treatment regimen.
Conclusions
El‐Khalawany et al. conclude that both methotrexate and ciclosporin in low doses are clinically effective, relatively safe, and well tolerated as treatments for severe atopic eczema in children.
Background
Chronic inflammatory skin diseases such as atopic dermatitis (AD) and psoriasis (PSO) present major challenges in health care. Thus, biomarkers to identify disease trajectories and ...response to treatments to improve the lives of affected individuals warrant great research consideration. The requirements that these biomarkers must fulfil for use as practical clinical tools have not yet been adequately investigated.
Aim
To identify the core elements of high‐quality AD and PSO biomarkers to prepare recommendations for current biomarker research.
Method
A cross‐sectional two‐round Delphi survey was conducted from August to October 2019 and October to November 2020. All participants were members of the BIOMAP project, an EU‐funded consortium of clinicians, researchers, patient organizations and pharmaceutical industry partners. The first round consisted of three open‐ended questions. Responses were qualitatively analysed, and 26 closed statements were developed. For the second round, ‘agreement’ was assumed when the responses of ≥70% of the participants were ≥5 points on a 7‐point Likert scale for each statement. Priority classification was based on mean scores (<20th percentile = low, 20th to 60th percentile = medium, >60th percentile = high).
Results
Twenty‐one and twenty‐six individuals participated in rounds one and two, respectively. From 26 statements that were included in round 2, 18 achieved agreement (8 concerning the performance, 8 for the purpose and 2 on current obstacles). Seven statements were classified as high priority, e.g. those concerning reliability, clinical validity, a high positive predictive value, prediction of the therapeutic response and disease progression. Another seven statements were assigned medium priority, e.g. those about analytical validity, prediction of comorbidities and therapeutic algorithm. Low priority included four statements, like those concerning cost effectiveness and prediction of disease flares.
Conclusion
The core requirements that experts agreed on being essential for high‐quality AD and PSO biomarkers require rapid validation. Biomarkers can therefore be assessed based on these prioritized requirements.
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