Eleanor Samarasekera

Incidence of Cardiovascular Disease in Individuals with Psoriasis: A Systematic Review and Meta-Analysis

The relationship between psoriasis and increased risk of cardiovascular disease (CVD) is controversial. We critically evaluate 14 cohorts and meta-analyze the magnitude of CVD risk for the primary outcomes of CVD mortality, stroke, and myocardial infarction (MI), and establish subgroup risk for different psoriasis severities and age groups. Increased CVD risk was identified only in individuals with severe psoriasis (defined as requiring systemic therapy or hospital admission): the risk ratio relative to the general population was 1.37 (95% confidence interval (CI) 1.17-1.60) for CVD mortality, 3.04 (95% CI 0.65-14.35) for MI, and 1.59 (95% CI 1.34-1.89) for stroke. The relative risks of CVD were highest in the younger, severe psoriasis population (e.g., 3.10 (95% CI 1.98-4.86) for MI at 30 years), and absolute risks were greatest in older individuals with severe psoriasis (e.g., 23.2 excess MIs per 10,000 person-years at 60 years). Uncertainty remains about whether CVD risk is directly attributable to psoriasis, as the majority of studies failed to adequately adjust for key traditional risk factors.

Topical therapies for the treatment of plaque psoriasis: systematic review and network meta-analyses

The majority of people with psoriasis have localized disease, where topical therapy forms the cornerstone of treatment. We set out to summarize evidence on the relative efficacy, safety and tolerability of different topical treatments used in plaque psoriasis. We undertook a systematic review and meta‐analyses of randomized trial data of U.K.‐licensed topical therapies. The primary outcome was clear or nearly clear status stratified for (i) trunk and limbs; and (ii) scalp. Network meta‐analyses allowed ranking of treatment efficacy. In total, 48 studies were available for trunk and limb psoriasis, and 17 for scalp psoriasis (22 028 patients in total); the majority included people with at least moderate severity psoriasis. Strategies containing potent corticosteroids (alone or in combination with a vitamin D analogue) or very potent corticosteroids dominated the treatment hierarchy at both sites (trunk and limbs, scalp); coal tar and retinoids were no better than placebo. No significant differences in achievement of clear or nearly clear status were observed between twice‐ and once‐daily application of the same intervention or between any of the following: combined vitamin D analogue and potent corticosteroid (applied separately or in a single product), very potent corticosteroids, or potent corticosteroids (applied twice daily). Investigator and patient assessment of response differed significantly for some interventions (response rates to very potent corticosteroids: 78% and 39%, respectively). No significant differences were noted for tolerability or steroid atrophy, but data were limited. In conclusion, corticosteroids are highly effective in psoriasis when used continuously for up to 8 weeks and intermittently for up to 52 weeks. Coal tar and retinoids are of limited benefit. There is a lack of long‐term efficacy and safety data available on topical interventions used for psoriasis.

Assessment and management of psoriasis: summary of NICE guidance

Psoriasis is a common inflammatory skin condition affecting about 1.3–2.2% of the UK population1 and may be associated with psoriatic arthritis.2 People with psoriasis, especially those with severe disease, are also at increased risk of cardiovascular disease,3 diabetes,4 and depression.5 Psoriasis may result in functional, psychological, and social morbidity, even in people with minimal involvement (less than the equivalent of three palm areas). However, doctors, including dermatologists, often fail to appreciate the extent of this disability,6 and many people with psoriasis are dissatisfied with their treatment.6 Yet, highly effective and cost effective treatments are available, and improving outcomes therefore requires better assessment and management of psoriasis, including its impact on a patient’s wellbeing, by healthcare professionals. This article summarises the most recent recommendations from the National Institute for Health and Clinical Excellence (NICE) on the management of psoriasis.7 NICE recommendations are based on systematic reviews of the best available evidence and explicit consideration of cost effectiveness. When minimal evidence is available, recommendations are based on the Guideline Development Group’s experience and opinion of what constitutes good practice. Evidence levels for the recommendations are given in italic in square brackets. ### Principles of care [Based on the experience and opinion of the Guideline Development Group (GDG)] ### Assessment of disease severity and impact, and when to refer for specialist care [Based on the experience and opinion of the GDG]

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).

Diagnostic accuracy of noninvasive markers of liver fibrosis in patients with psoriasis taking methotrexate: a systematic review and meta-analysis†

People with psoriasis taking methotrexate may be at increased risk of developing liver fibrosis compared with the general population. Noninvasive methods of detecting fibrosis have been widely adopted but their clinical utility is uncertain. To evaluate the diagnostic accuracy of noninvasive methods to detect fibrosis compared with liver biopsy (reference standard) in people with psoriasis taking methotrexate. A systematic search using Ovid/Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, the Cochrane Library and Clinical Trials Register was performed. Diagnostic cohorts or case–control studies of adults taking or being considered for methotrexate therapy were considered. Study quality was evaluated using the Quality Assessment tool for Diagnostic Accuracy Studies (QUADAS‐2). Pooled data analysis was performed using RevMan 5.1. Bayesian meta‐analysis was conducted using Markov chain Monte Carlo simulation. Seventeen studies were included. Sensitivity and specificity were 38% and 83% for standard liver function tests (LFTs), 74% and 77% for procollagen‐3 N‐terminal peptide (P3NP), 60% and 80% for Fibroscan® (Echosens, France, www.echosens.com), and 55% and 49% for ultrasound. Confidence in these results is limited owing to low‐quality data; old, small studies displayed significant selection bias and significant variation in the prevalence of fibrosis. No studies were identified evaluating recently developed markers. The clinical utility of LFTs, P3NP and liver ultrasound is poor. Therefore if these tests are used in isolation, a significant proportion of patients with liver fibrosis may remain unidentified. Larger prospective studies are required in this population to validate newer non‐invasive methods.

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.

Topical therapies for the treatment of localized plaque psoriasis in primary care: a cost‐effectiveness analysis

Topical therapies are a mainstay of psoriasis treatment, but they vary substantially in terms of cost.

Psoriasis: guidance on assessment and referral

This concise guideline summarises the key recommendations from the recent National Institute for Health and Care Excellence (NICE) clinical guideline on the assessment and management of psoriasis (CG153) that are relevant to the non-dermatologist. The aim is to highlight important considerations for assessment and referral of people with psoriasis, including identification of relevant comorbid conditions. Psoriasis is a common inflammatory skin condition and, especially when severe, can be associated with increased risk of cardiovascular disease, diabetes and depression. Functional, psychological and social morbidity can also be encountered, and the extent of the disability is frequently underestimated. Importantly, highly effective treatments are available. Appropriate assessment and referral of people with psoriasis therefore has the potential to improve outcomes by correctly identifying the appropriate treatment pathway. Assessment should involve not only disease severity but also the impact on patient well-being and whether the patient has any comorbid conditions, such as psoriatic arthritis, which requires rapid referral to a rheumatologist.

Pancreatitis: summary of NICE guidance

### What you need to know Pancreatitis can severely reduce quality of life and may reduce life expectancy.12 Acute and chronic pancreatitis are characterised by inflammation of the pancreas, and table 1 outlines their features. Acute pancreatitis can recur if the cause is not identified and addressed. Over time, such patients may develop chronic pancreatitis. In its early stages this is characterised by acute exacerbations but also chronic pain, along with exocrine insufficiency, associated with fat malabsorption and malnutrition. Diabetes is also common. As chronic pancreatitis progresses, patients tend to experience fewer exacerbations but more chronic pain. View this table: Table 1 Features of acute and chronic pancreatitis Specialists almost always manage acute pancreatitis because it is an acute abdominal emergency requiring hospital admission. However, non-specialists, including those in primary care, may be the first clinicians to identify chronic pancreatitis. Non-specialists may also manage and monitor symptoms including pain, endocrine and exocrine insufficiency, and make appropriate referrals. Interventions used for management of acute pancreatitis show wide variation.3 Advice on management is often conflicting, and some patients have had difficulty accessing appropriate care. The new national guideline from the National Institute for Health and Care Excellence (NICE) on pancreatitis aims …