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Summary: This review provides a summary of key findings from 27 systematic reviews of 51 articles first published or indexed during 2015, focusing on the treatment of psoriasis and on precision medicine in psoriasis. The evidence supports weight‐loss interventions by dieting and exercise for improvement in disease severity in overweight and obese patients with psoriasis. No significant increased risk of serious infections was reported for the biologic therapies adalimumab, etanercept and ustekinumab compared with appropriate comparators. Evidence could not provide reliable estimates of rare adverse events, emphasizing the need for large prospective registries. Polymorphisms in the tumour necrosis factor (TNF)‐α gene may confer improved responses to TNF inhibitor (TNFI) therapy, but the studies to date lack power to detect a true association. From the limited available evidence, multidisciplinary management is both more effective and more satisfactory for patients with psoriasis and psoriatic arthritis than conventional consultations. This summary of reviews provides a succinct guide for clinicians and patients wishing to remain up to date with high‐quality evidence for the treatment of psoriasis. [ABSTRACT FROM AUTHOR]

Summary: Background: Head‐to‐head randomized studies comparing ixekizumab and secukinumab in the treatment of psoriasis are not available. Objectives: To assess efficacy and quality of life using matching‐adjusted indirect comparisons for treatment with ixekizumab vs. secukinumab. Methods: Psoriasis Area and Severity Index (PASI) improvement of at least 75%, 90% and 100% and Dermatology Life Quality Index (DLQI) 0/1 response rates for approved dosages of ixekizumab (160 mg at Week 0, then 80 mg every two weeks for the first 12 weeks) and secukinumab (300 mg at Weeks 0, 1, 2, 3 and 4, then 300 mg every 4 weeks) treatment were compared using data from active (etanercept and ustekinumab) and placebo‐controlled studies. Comparisons were made using the Bucher (BU) method and two modified versions of the Signorovitch (SG) method (SG total and SG separate). Subsequently, results based on active treatment common comparators were combined using generic inverse‐variance meta‐analysis. Results: In the meta‐analysis of studies with active comparators, PASI 90 response rates were 12·7% [95% confidence interval (CI) 5·5–19·8, P = 0·0005], 10·0% (95% CI 2·1–18·0, P = 0·01) and 11·2% (95% CI 3·2–19·1, P = 0·006) higher and PASI 100 response rates were 11·7% (95% CI 5·9–17·5, P < 0·001), 12·7% (95% CI 6·0–19·4, P < 0·001) and 13·1% (95% CI 6·3–19·9, P < 0·001) higher for ixekizumab compared with secukinumab using BU, SG total and SG separate methods. PASI 75 results were comparable when SG methods were used and favoured ixekizumab when the BU method was used. Week 12 DLQI 0/1 response rates did not differ significantly. Conclusions: Ixekizumab had higher PASI 90 and PASI 100 responses at week 12 compared with secukinumab using adjusted indirect comparisons. [ABSTRACT FROM AUTHOR]

An evaluation of dermatology patients shielding during the COVID-19 outbreak Retrospective analysis of patient records/pharmacy lists revealed 1071 patients that met the British Association of Dermatologists' criteria for shielding.4 Printed letters were posted to these patients, advising them accordingly. In conclusion, the majority of our highly vulnerable dermatology patients shielded, continued to take their immunosuppressive medication and denied any symptoms of COVID-19. [Extracted from the article]

Summary [ABSTRACT FROM AUTHOR]

Psoriasis is associated with significant physical, psychological, social and economic burden, the cumulative effect of which may result in failure to achieve 'full life potential' in some patients, termed 'cumulative life course impairment' (CLCI). In this concept, the burden of stigmatization, and physical and psychological comorbidities (risk factors for cumulative impairment) and coping strategies and external factors (having potential moderating effects), interact to cause lifetime impairment. Components of CLCI are supported by cross-sectional data; however, the cumulative nature of impairment in patients with psoriasis is not yet established. Nonetheless, CLCI makes intuitive sense to many dermatologists who recognize the cumulative impact of psoriasis on the lives of some patients. This supplement explores the causes and mechanisms of CLCI qualitatively by presenting cases which are representative of typical patients with moderate-to-severe psoriasis. These cases demonstrate the effect of psoriasis in influencing major life-changing decisions and altering the course of patients' lives, preventing patients from attaining their life goals, pursuing their chosen career, gaining a desired educational level, developing social relationships, gaining full pleasure from family life or having children. All these patients believe that their lives would have taken a different course had they not had psoriasis. Additional research to determine how CLCI occurs and to identify the risk factors for cumulative impairment is required. Understanding the key risk factors for CLCI may help physicians identify patients who are more vulnerable to the cumulative impact of psoriasis, resulting in more appropriate treatment decisions earlier in the disease course. [ABSTRACT FROM AUTHOR]

Background There are few reports of the practical use of adalimumab outside a clinical trial setting and, to our knowledge, none from the U.K. Objectives We assessed the efficacy and safety of adalimumab in a cohort of patients with severe psoriasis attending a tertiary dermatology referral centre in the U.K. Methods A retrospective case-note review was used to identify all patients initiated on adalimumab for psoriasis. Results Mean ± SD baseline Psoriasis Area and Severity Index (PASI) score was 24 ± 11 (range 9-54; n = 46). After 4 months' treatment with adalimumab, 64% (29/45) of patients had achieved PASI 75 (75% decrease from baseline) while 80% (36/45) of patients met National Institute for Health and Clinical Excellence (NICE) criteria for continuation of treatment. The therapy was well tolerated. Importantly, 68% (21/31) of patients who had previously received another tumour necrosis factor-α inhibitor met NICE criteria for continuation of treatment at 16 weeks. Conclusions In a cohort of U.K. patients with severe psoriasis, adalimumab has proved to be a significant addition to the expanding armamentarium of biologics for psoriasis. Pharmacovigilance, in the form of registries, is essential to assess the long-term safety of such drugs. [ABSTRACT FROM AUTHOR]

This review summarizes the clinical importance of 18 systematic reviews and guidelines on psoriasis published or indexed between November 2008 and October 2009. The topics covered include guidance on the use of topical, systemic and biological therapies for the treatment of psoriasis; comorbidities associated with psoriasis; and complementary therapies for psoriasis. A similar and more detailed review to this appeared in the 2009 Annual Evidence Update on Psoriasis from NHS Evidence – Skin Disorders in November 2009. [ABSTRACT FROM AUTHOR]

This review summarizes the clinical importance of six systematic reviews on psoriasis published between January 2007 and October 2008. A meta-analysis demonstrated that several traditional nonbiological systemic therapies have equal or superior efficacy to some biological therapies used in the treatment of psoriasis. Two further meta-analyses comparing biological therapies for psoriasis (excluding adalimumab) have established a hierarchy of efficacy for short-term treatment (10–16 weeks): infliximab > etanercept 50 mg twice weekly > etanercept 25 mg twice weekly > efalizumab > alefacept. Excluding adalimumab, rates of adverse events are significantly higher for biological therapies than for placebo, except for etanercept at both 25 and 50 mg twice weekly. Further, head to head trials of biological therapies for psoriasis and longer-term safety data on their use are required. Psoriasis can be induced by and/or exacerbated during antitumour necrosis factor (TNF) therapy. It is recommended to initially switch anti-TNF agent in this situation and only discontinue therapy if psoriasis is extensive and/or intolerable, allowing the primary disease to remain under control. Most screening and monitoring tests carried out during treatment of psoriasis with biological therapies are neither supported nor refuted by current evidence and the clinician must assess each case individually. Studies designed specifically to assess appropriate use of these tests are required. Further research is needed to evaluate the effectiveness of existing psychological interventions in psoriasis. The effectiveness of support groups has not been adequately proven, although there are limited data supporting the use of cognitive behavioural therapy. [ABSTRACT FROM AUTHOR]

Background The use of methotrexate is limited by interindividual variability in response. Previous studies in patients with either rheumatoid arthritis or psoriasis suggest that genetic variation across the methotrexate metabolic pathway might enable prediction of both efficacy and toxicity of the drug. Objectives To assess if single nucleotide polymorphisms (SNPs) across four genes that are relevant to methotrexate metabolism [folypolyglutamate synthase ( FPGS), gamma-glutamyl hydrolase ( GGH), methylenetetrahydrofolate reductase ( MTHFR) and 5-aminoimidazole-4-carboxamide ribonucleotide transformylase ( ATIC)] are related to treatment outcomes in patients with psoriasis. Methods DNA was collected from 374 patients with psoriasis who had been treated with methotrexate. Data were available on individual outcomes to therapy, namely efficacy and toxicity. Haplotype-tagging SNPs ( r2 > 0·8) for the four genes with a minor allele frequency of > 5% were selected from the HAPMAP phase II data. Genotyping was undertaken using the MassARRAY spectrometric method (Sequenom®). Results There were no significant associations detected between clinical outcomes in patients with psoriasis treated with methotrexate and SNPs in the four genes investigated. Conclusions Genetic variation in four key genes relevant to the intracellular metabolism of methotrexate does not appear to predict response to methotrexate therapy in patients with psoriasis. [ABSTRACT FROM AUTHOR]

Background Large-scale clinical trials provide clear evidence of the efficacy and short-term toxicity of biologic therapies for psoriasis. However, to date, there are few reports of the practical use of these therapies outside of the trial setting and, to our knowledge, none from a U.K. cohort of patients with psoriasis. Objectives (i) To assess efficacy and safety of efalizumab, etanercept and infliximab in a U.K. cohort of patients with psoriasis, with mean Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index 21·8 and 21·7, respectively, outside of the clinical trial setting. (ii) To examine our approach to the processes involved in the initiation of biologic therapies in the era of National Institute for Health and Clinical Excellence guidance. Methods A retrospective case-note review to identify all patients initiated on biologic therapies for psoriasis in a U.K. tertiary referral centre. Results At 3 months of treatment the efficacy of efalizumab ( n = 28), etanercept ( n = 70) and infliximab ( n = 20), as assessed by PASI 75 (75% decrease from baseline score), was 24%, 35% and 85%, respectively. All three biologics used were well tolerated. Combination therapy with traditional systemic agents was required either at transition to, or to counter relapse while established on, a biologic therapy in 30% of cases. Streamlined approaches to screening and funding significantly ( P ≤ 0·05) hastened the initiation of biologic therapies. Conclusions In a cohort of U.K. patients with severe psoriasis, biologic therapies have proved to be a significant step forward in expanding the therapeutic armamentarium for psoriasis. Pharmacovigilance, in the form of registries, is essential to assess the long-term safety of such drugs. [ABSTRACT FROM AUTHOR]

Methotrexate’s traditional role as a first line agent for moderate to severe psoriasis is being challenged by the rapid and growing use of biological therapies. A recent study comparing adalimumab with methotrexate showed significantly superior efficacy of adalimumab over methotrexate over 16 weeks. Although it is inexpensive, the future use of methotrexate may be compromised by its unpredictable response and toxicity, and by the introduction of newer, more effective biological therapies. However, recent advances in the screening of liver fibrosis by monitoring serum levels of the aminoterminal peptide fragment of type III procollagen have reduced the need for liver biopsy. Furthermore, the potential for personalized methotrexate use by application of modern pharmacogenetics and pharmacokinetics may ensure its place as a first-line agent for the treatment of psoriasis for the foreseeable future. [ABSTRACT FROM AUTHOR]

Background  Psoriasis, a chronic inflammatory skin disease, affects approximately 2% of the population worldwide. Although the aetiology of psoriasis is poorly understood, patients with disease of early onset (Type I, age of onset ≤ 40 years) usually have a strong genetic component to the disease. Objectives  The purpose of this study was to investigate the role of the protein tyrosine phosphatase nonreceptor type 22 ( PTPN22) gene region in susceptibility to Type I psoriasis. Patients and methods  Thirteen single nucleotide polymorphisms (SNPs) mapping to the PTPN22 region were genotyped in 647 patients with Type I psoriasis and 566 normal controls. Results  The rs2476601 (R620W) SNP, widely associated with other inflammatory autoimmune diseases, showed no evidence of association with susceptibility to Type I psoriasis. Two SNPs (rs1217414 and rs3789604) demonstrated significant association with Type I psoriasis and were subsequently genotyped in a further 253 unrelated patients and 2024 normal controls. rs1217414 and rs3789604 were also significantly associated with Type I psoriasis in the combined datasets ( P = 0·003 and P = 0·0002, respectively); furthermore carriage of both risk alleles was also significantly associated ( P = 0·002). Conclusions  This study demonstrates evidence of association of two SNPs (rs1217414 and rs3789604) in the PTPN22 region with Type I psoriasis, providing evidence for a role of this gene in Type I psoriasis that is not conferred by the R620W variant previously associated with a number of inflammatory diseases. [ABSTRACT FROM AUTHOR]

The study of pharmacogenetics will optimize the use of systemic therapies in dermatology. Directed prescription of azathioprine dependent on phenotypic expression of the thiopurine methyltransferase gene is now accepted practice. To some extent other, older drugs have been neglected. We look at the role that pharmacogenetics could play in the use of methotrexate for psoriasis, focusing on known polymorphisms in the folate metabolic pathway. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which discusses the effectiveness of combining infliximab and methotrexat to obtain a long-term control of recalcitrant psoriasis.