Ruth Murphy

British Association of Dermatologists guidelines for biologic therapy for psoriasis 2017

The overall aim of the guideline is to provide evidence-based recommendations on the use of biologic therapies (adalimumab, etanercept, infliximab, ixekizumab, secukinumab and ustekinumab) in adults, children and young people for the treatment of psoriasis; consideration is given to the specific needs of people with psoriasis and psoriatic arthritis. Biologic therapies have now been in use for over 10 years, and with accrued patient-years exposure and clinical experience, many areas that were covered in previous versions of the guideline are now part of the Summary of Product Characteristics (SPC) and/or routine care so that specific recommendations are redundant (see Toolkit A: Summary of licensed indications and posology for biologic therapy, in Supporting information 2). Therefore, in this update we focus on areas where there has been a major change in the evidence base or clinical practice, where practice is very varied and/or where clear consensus or guidelines are lacking (see section 3.1 in Supporting information 1).

Quantitative Evaluation of Biologic Therapy Options for Psoriasis: A Systematic Review and Network Meta-Analysis

Multiple biologic treatments are licensed for psoriasis. The lack of head-to-head randomized controlled trials makes choosing between them difficult for patients, clinicians, and guideline developers. To establish their relative efficacy and tolerability, we searched MEDLINE, PubMed, Embase, and Cochrane for randomized controlled trials of licensed biologic treatments for skin psoriasis. We performed a network meta-analysis to identify direct and indirect evidence comparing biologics with one another, methotrexate, or placebo. We combined this with hierarchical cluster analysis to consider multiple outcomes related to efficacy and tolerability in combination for each treatment. Study quality, heterogeneity, and inconsistency were evaluated. Direct comparisons from 41 randomized controlled trials (20,561 participants) were included. All included biologics were efficacious compared with placebo or methotrexate at 3–4 months. Overall, cluster analysis showed adalimumab, secukinumab, and ustekinumab were comparable in terms of high efficacy and tolerability. Ixekizumab and infliximab were differentiated by very high efficacy but poorer tolerability. The lack of longer term controlled data limited our analysis to short-term outcomes. Trial performance may not equate to real-world performance, and so results need to be considered alongside real-world, long-term safety and effectiveness data. These data suggest that it is possible to discriminate between biologics to inform clinical practice and decision making (PROSPERO 2015:CRD42015017538).

Practical experience of ustekinumab in the treatment of psoriasis: Experience from a multicentre, retrospective case cohort study across the U.K. and Ireland

Background  There are limited data on the use of ustekinumab outside of clinical trials.

Risk of Serious Infections in Patients with Psoriasis on Biologic Therapies: A Systematic Review and Meta-Analysis

A comprehensive evaluation of the risk of serious infections in biologic therapies for psoriasis is lacking. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) and prospective cohort studies reporting serious infections in people taking any licensed biologic therapy for psoriasis compared with those taking placebo, nonbiologic therapy, or other biologic therapies. The quality of the studies was assessed using Grading of Recommendations Assessment, Development and Evaluation criteria. No significant heterogeneity was detected in data from 32 RCTs (n = 13,359 participants) and one cohort study (n = 4,993 participants). In adults, low- to very-low-quality RCT data showed no significant difference between any biologic therapy and placebo at weeks 12–16 (overall pooled Peto odds ratio = 0.71, 95% confidence interval = 0.36–1.41) and weeks 20–30 (odds ratio = 2.27, 95% confidence interval = 0.45–11.49). No significant differences were found in any of the other comparisons in underpowered RCT data. Prospective cohort study data of low quality suggests that only adalimumab (adjusted hazard ratio [adjHR] = 2.52, 95% confidence interval = 1.47–4.32) was associated with a significantly higher risk of serious infection compared with retinoid and/or phototherapy in adults. No association between biologic therapies and serious infections in patients with psoriasis who were eligible for RCTs was detected. Further observational studies are needed to inform the uncertainty around this risk in the real world.

Risk of Serious Infection in Patients with Psoriasis on Biologic Therapies: a Prospective Cohort Study from the British Association of Dermatologists Biologic Interventions Register (BADBIR)

Serious infection is a concern for patients with psoriasis receiving biologic therapies. We assessed the risk of serious infections for biologics used to treat psoriasis by comparison with a cohort receiving non-biologic systemic therapies in a propensity score-weighted Cox proportional hazards model using data from the British Association of Dermatologists Biologic Interventions Register. Overall, 1,352; 3,271; and 994 participants were included in the etanercept, adalimumab, ustekinumab cohorts, respectively, and 3,421 participants were in the non-biologic cohort. A total of 283 patients had a serious infection; the incidence rates with 95% confidence intervals (CI) per 1,000 person-years were as follows: non-biologic, 14.2 (11.5–17.4); etanercept, 15.3 (11.6–20.1); adalimumab, 13.9 (11.4–16.6); and ustekinumab, 15.1 (10.8–21.1). No significant increases in the risk of serious infection were observed for etanercept (hazard ratio [HR] = 1.10, 95% CI = 0.75–1.60), adalimumab (HR = 0.93, 95% CI = 0.69–1.26), or ustekinumab (HR = 0.92, 95% CI = 0.60–1.41) compared with non-biologic systemic therapies or methotrexate-only (etanercept: HR = 1.47, 95% CI = 0.95–2.28; adalimumab: HR = 1.26, 95% CI = 0.86–1.84; ustekinumab: HR = 1.22, 95% CI = 0.75–1.99). The risk of serious infection should not be a key discriminator for patients and clinicians when choosing between non-biologic systemic therapies, etanercept, adalimumab, and ustekinumab for the treatment of psoriasis.

(25) Skin surface markings: an aid to diagnosis in dysplastic naevi and malignant melanoma

A number of distinct clinical entities are characterized by subepidermal blisters in association with linear deposition of immune reactants at the basement membrane zone (BMZ) of skin and mucous membranes. In addition to the clinical differences, further divisions are made on the basis of class of immunoreactants and the ultrastructural site of the immune deposits in relation to the BMZ, i.e. whether in the lamina lucida or below the lamina densa. We present Western blotting studies on patients with bullous pemphigoid (BP) (53), cicatricial pemphigoid (CP) (20), pemphigoid gestationis (PG) (34), linear IgA disease (LAD) of children (18), and adults (five), epidermolysis bullosa acquisita (EBA) (four) and lichen planus pemphigoides (LPP) (six). These 140 patients were classified clinically and by direct immunofiuorescence (IMF) and indirect IMF on intact and i M NaCl split skin prior to blotting. All the lamina lucida bullous diseases showed heterogeneity and overlap of epidermal antigens. Sera from the majority of typical BP patients (39%) reacted with the previously described 220 kDa BP glycoprotein, a significant minority (8%) reacted with antigens of 180 kDa (shared with PG) (6%) and 309 kDa (2%). The majority of PG sera reacted with a 180 kDa antigen (21%) and a minority also with the 220 kDa BP antigen (9%). Lichen planus pemphigoides sera also demonstrated reactivity with the 180 kDa antigen (66%) and a unique 200 kDa antigen (66%). Cicatricial pemphigoid sera also reacted with the 220 kDa antigen. Distinctive dermal antigens were identified for EBA/type VII collagen (250 kDa) and LAD (285 kDa). The molecular overlap as regards the target antigen in the blistering diseases with IgG antibodies in the lamina lucida may explain the clinical similarities. The heterogeneous nature of the antigens may also account for the diverse clinical presentations of BP. Although EBA may present clinically as BP it does not share a common antigen and no overlap with LAD has been observed. However, the antigen alone is not the sole determinant of the clinical presentation, and the host response must also be of major importance.

The management of vulval itching caused by benign vulval dermatoses

This article will cover key points in patient assessment, vulval examination and treatment of vulval disease, specifically dermatological conditions. Often, simple measures can benefit the patient (e.g. use of emollients). However, many women have complex disease with more than one condition, so careful assessment and individualised management is essential. Some gynaecologists have unmet training needs in the assessment and management of vulval skin disease. It is important to assess patients and then refer difficult cases and non‐responders to a vulval service for a multidisciplinary opinion.

Infliximab is associated with an increased risk of serious infection in patients with psoriasis in the United Kingdom and Republic of Ireland: results from the British Association of Dermatologists Biologic Interventions Register (BADBIR).

Patients with psoriasis and clinicians are concerned that infliximab may be associated with a risk of serious infections.