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Background: Certolizumab pegol (CZP) is an Fc‐free, PEGylated anti‐tumor necrosis factor biologic. Objectives: To report 3‐year outcomes from the CIMPACT (NCT02346240) phase 3, CZP in moderate to severe plaque psoriasis, randomized controlled trial. Methods: Adults were randomized 3:3:3:1 to CZP 200 mg every other week (Q2W), CZP 400 mg Q2W, etanercept biweekly or placebo. At Week 16, CZP‐ and etanercept‐treated PASI 75 responders were re‐randomized to CZP 200 mg Q2W, CZP 400 mg Q4W, CZP 400 mg Q2W or placebo for maintenance treatment; PASI 75 non‐responders entered an open‐label escape CZP 400 mg Q2W arm. Patients entering the open‐label extension (OLE; Weeks 48–144) from blinded treatment received CZP 200 mg Q2W. Results: Double‐blinded results have been reported previously. 261 patients received 200 mg Q2W upon OLE entry. PASI 75 response was maintained in patients continuing 200 mg Q2W treatment through Weeks 16–144 (Week 144: 96.2%). In patients dosed down at Week 48 (double‐blinded 400 mg to 200 mg Q2W), PASI 75 decreased (Week 48: 98.7%; Week 144: 85.9%). In patients who received placebo through Weeks 16–48, PASI 75 response decreased (Week 48: 60.4%), then increased following Week 48 switch to 200 mg Q2W (Week 144: 95.1%). 48 and 36 patients initially randomized to 200 and 400 mg Q2W, respectively, were Week 16 PASI 75 non‐responders and entered the escape arm; at Week 144, 71.8% and 78.2% achieved PASI 75. No new safety signals were identified. Conclusions: Response to CZP was durable over three years; no new safety signals were identified. [ABSTRACT FROM AUTHOR]

Background: Bimekizumab is a monoclonal IgG1 antibody that selectively inhibits interleukin-17A and interleukin-17F. The efficacy and safety of bimekizumab as compared with the tumor necrosis factor inhibitor adalimumab in patients with moderate-to-severe plaque psoriasis have not been extensively examined.Methods: We randomly assigned patients with moderate-to-severe plaque psoriasis in a 1:1:1 ratio to receive subcutaneous bimekizumab at a dose of 320 mg every 4 weeks for 56 weeks; bimekizumab at a dose of 320 mg every 4 weeks for 16 weeks, then every 8 weeks for weeks 16 to 56; or subcutaneous adalimumab at a dose of 40 mg every 2 weeks for 24 weeks, followed by bimekizumab at a dose of 320 mg every 4 weeks to week 56. The primary end points were a 90% or greater reduction from baseline in the Psoriasis Area and Severity Index (PASI) score (PASI 90 response; PASI scores range from 0 to 72, with higher scores indicating worse disease) and an Investigator's Global Assessment (IGA) score of 0 or 1, signifying clear or almost clear skin (scores range from 0 [clear skin] to 4 [severe disease]), at week 16. The analysis of the primary end points tested noninferiority at a margin of -10 percentage points and then tested for superiority.Results: A total of 614 patients were screened, and 478 were enrolled; 158 patients were assigned to receive bimekizumab every 4 weeks, 161 to receive bimekizumab every 4 weeks and then every 8 weeks, and 159 to receive adalimumab. The mean age of the patients was 44.9 years; the mean PASI score at baseline was 19.8. At week 16, a total of 275 of 319 patients (86.2%) who received bimekizumab (both dose groups combined) and 75 of 159 (47.2%) who received adalimumab had a PASI 90 response (adjusted risk difference, 39.3 percentage points; 95% confidence interval [CI], 30.9 to 47.7; P<0.001 for noninferiority and superiority). A total of 272 of 319 patients (85.3%) who received bimekizumab and 91 of 159 (57.2%) who received adalimumab had an IGA score of 0 or 1 (adjusted risk difference, 28.2 percentage points; 95% CI, 19.7 to 36.7; P<0.001 for noninferiority and superiority). The most common adverse events with bimekizumab were upper respiratory tract infections, oral candidiasis (predominantly mild or moderate as recorded by the investigator), hypertension, and diarrhea.Conclusions: In this 56-week trial, bimekizumab was noninferior and superior to adalimumab through 16 weeks in reducing symptoms and signs of plaque psoriasis but was associated with a higher frequency of oral candidiasis and diarrhea. Longer and larger trials are required to determine the efficacy and safety of bimekizumab as compared with other agents in the treatment of plaque psoriasis. (Funded by UCB Pharma; BE SURE ClinicalTrials.gov number, NCT03412747.). [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]

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]

Tuberculosis (TB), caused by Mycobacterium tuberculosis, is a significant global health problem. In immunocompetent individuals, the microorganism can remain in a latent, non‐contagious form, however, it may become active under conditions of immunosuppression. Tumour necrosis factor (TNF) inhibitors, which are frequently used for the management of immune‐mediated disorders like psoriasis, have been associated with a significantly increased risk of reactivating latent TB. Consequently, international guidelines recommend TB screening and preventive treatment before starting anti‐TNF therapy. These recommendations have extended to IL‐12/23, IL‐17, IL‐23 and TYK2 inhibitors under a caution principle, despite their different mechanisms of action. However, current evidence suggests that some of these agents are arguably not associated with an increased risk of TB reactivation or development of TB disease after infection, which calls for a critical reassessment of these guidelines. We have conducted a literature search evaluating the risk of TB reactivation associated with these innovative therapies, integrating findings from both randomized clinical trials and real‐world evidence. The identified evidence is limited but the low number of identified cases of reactivation with IL‐17 and IL‐23 inhibitors prompts reconsidering the need for preventive treatment for latent TB in all cases, regardless of biologic class or individual patient's risk of TB reactivation or drug toxicity. This review, along with the clinical insight of a panel of experts on behalf of the SPIN‐FRT, led to the development of these consensus recommendations for managing psoriasis treatment in patients with latent TB infection or at risk of TB infection, who are receiving or are intended to receive biologic and non‐biologic targeted therapies. These recommendations highlight the need for updates to the existing guidelines, aiming to provide a more differentiated approach that reflects the evolving landscape of psoriasis treatment and its implications for TB management. [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.

A letter to the editor is presented which discusses the reaction of recalcitrant necrobiosis lipoidica when treated with combined immunosuppression therapy.

Porokeratotic eccrine ostial and dermal duct nevus is a rare disorder characterized by distinctive histopathology. We describe a 6-year-old boy who had the typical palmar involvement and small discrete areas involving the midline of his back. [ABSTRACT FROM AUTHOR]

Psoriasis is commonly associated with a co-existent arthritis known as psoriatic arthritis (PsA). Although there is some treatment overlap for psoriasis and psoriatic arthritis, it is possible that dermatologists may not diagnose or treat appropriately patients who are developing psoriatic arthritis at an early stage of the disease process when joint damage may be preventable. In this article we review the criteria for diagnosis of this sero-negative arthritis, look at the clinical indications for referral to a rheumatologist and discuss evolving treatment options relevant to both conditions. [ABSTRACT FROM AUTHOR]

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]

Abstract: Fumaric acid esters (FAEs) are a group of small molecules that were first investigated for the treatment of psoriasis in 1959. The first fumarate‐based drug – Fumaderm® – was approved in Germany in 1994 for severe psoriasis and then in 2008, the label was expanded to include moderate psoriasis. Fumaderm is a combination of different FAEs: dimethyl fumarate (DMF), which is regarded as the main active component, plus calcium, magnesium and zinc salts of monoethyl fumarate (MEF). FAEs are the most frequently used first‐line systemic psoriasis treatment in Germany, with an overall treatment experience comprising more than 220 000 patient‐years. FAEs have demonstrated good, sustained clinical efficacy with an acceptable safety profile for the long‐term treatment of patients with moderate‐to‐severe psoriasis. Indeed, the European S3‐Guideline on the systemic treatment of Psoriasis vulgaris recommends FAEs for induction and long‐term treatment. Until recently, FAEs were only licensed (for the psoriasis indication) in Germany, but were imported to many other European countries, such as The Netherlands, UK, Ireland, Austria and Italy, for the treatment of psoriasis. In 2017, the European Medicines Agency (EMA) approved Skilarence®, a new oral formulation of DMF, for the treatment of adult patients with moderate‐to‐severe chronic plaque psoriasis in need of systemic therapy. Skilarence only contains DMF and is the first FAE for the treatment of psoriasis that has been approved by the EMA. This approval has given rise to a new oral treatment option for patients with moderate‐to‐severe plaque psoriasis across Europe. Here, we report the results of an expert meeting which was convened to deliver clinician‐agreed consensus and real‐world guidance on the clinical use of DMF in moderate‐to‐severe chronic plaque psoriasis. Guidance on appropriate patient selection, DMF dosage considerations, monitoring and side‐effect management is offered based upon available evidence and collective real‐world clinical experience. [ABSTRACT FROM AUTHOR]

Abstract: Background: Many patients with psoriasis have undiagnosed psoriatic arthritis. Low specificity is found with many PsA screening tools. A new instrument, the CONTEST questionnaire, was developed utilizing the most discriminative items from existing instruments. Objective: The aim of this study was to compare the CONTEST and PEST screening tools. Methods: People attending secondary care clinics with psoriasis, but not PsA, completed the questionnaires, were assessed for function and quality of life, and had a physical examination. Patients thought to have PsA were compared to those without. The performance of CONTEST and PEST was compared using area under the receiver operating curve (AUC), and sensitivity and specificity at the previously published cut‐offs. Results: A total of 451 dermatology patients were approached, 35% were reviewed and 27 (17%, 95% CI 12.3–21.7) had unidentified psoriatic arthritis. The sensitivity and specificity (95% CI) of PEST were 0.60 (0.42–0.78)/0.76 (0.69–0.83) and for CONTEST 0.53 (0.34–0.72)/0.71 (0.63–0.79). The confidence limits for the AUC overlapped (AUC for PEST 0.72 (0.61–0.84), for CONTEST 0.66 (0.54–0.77). Conclusions: PEST and CONTEST questionnaires performed equally well, with no superiority of the new CONTEST tool. [ABSTRACT FROM AUTHOR]

Despite the availability of a plethora of approved systemic treatments, high proportions of patients with moderate-to-severe psoriasis do not receive systemic treatment. This study aims at identifying barriers that hinder dermatologists from prescribing systemic treatments for psoriasis. A cross-sectional online survey in six countries (Canada, Germany, Spain, France, Italy, UK) was performed among 300 dermatologists, assessing the relevance of 15 potential barriers towards prescribing acitretin, cyclosporine, methotrexate, adalimumab, etanercept, infliximab and ustekinumab. Multivariate regression analyses were used to explore provider characteristics related to these barriers. Treatment barriers are perceived differently in the countries investigated, with Spanish, Italian and Canadian dermatologists being particularly concerned about the safety of methotrexate and Canadian dermatologists about the safety of cyclosporine. In general, safety concerns were the most important barrier to the use of cyclosporine, (18 % of participants’ moderate/9 % strong or very strong barrier). Costs were being perceived as a strong or very strong barrier to the use of the different biologics by 19–24 % of the participants. Overall, country and work place were the most important determinants of treatment barriers. Sex, age, training, position and experience were minor determinants of treatment barriers. Medical reasons such as safety concerns or an inappropriate risk-benefit profile are particularly relevant barriers to the prescription of conventional treatments; whereas for biological treatments, economic reasons such as costs are more prevalent. Country specific analysis showed national differences in the perception of safety. The treatment barriers identified in this exploratory study should be confirmed in further health services research. [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]

Experts in psoriasis, hepatology, pharmacokinetics and pharmacogenetics convened to discuss the safety and monitoring of methotrexate with respect to hepatotoxicity when used in the treatment of psoriasis. Methotrexate is an efficacious and cost-effective treatment for psoriasis, but is associated with significant safety issues, particularly relating to hepatotoxicity. Current British, Dutch, German, EU and US guidelines for baseline evaluations, monitoring and prevention of hepatotoxicity in patients with psoriasis receiving methotrexate were evaluated. Liver safety monitoring is currently reliant upon multiple methods, including biopsy, serological tests for biomarkers such as type III procollagen amino terminal propeptide (PIIINP), and liver function tests based on liver enzymes. Monitoring of patients receiving long-term therapy is expected to be improved by the utilization of serum biomarkers currently in development such as the Enhanced Liver Fibrosis (ELF) panel and other non-invasive tests of hepatic architecture, such as fibroelastography, microbubbles and magnetic resonance imaging. Appropriate studies to determine optimal dosing to maximize efficacy and minimize toxicity, potentially utilizing pharmacogenetic principles, are clearly needed. Key questions for future research are identified including needs for optimal screening and monitoring, identification of appropriate biomarkers, assessment of relationships between dosing and safety, utility of liver biopsy, optimal dosing regimens (including route of administration), methods to measure methotrexate levels in blood, and use of methotrexate as a standardized active comparator in trials of experimental drugs used to treat psoriasis. [ABSTRACT FROM AUTHOR]

Psoriasis is associated with significant physical and psychological burden affecting all facets of a patient’s life – relationships, social activities, work and emotional wellbeing. The cumulative effect of this disability may be self-perpetuating social disconnection and failure to achieve a ‘full life potential’ in some patients. Health-related quality of life studies have quantified the burden of psoriasis providing predominantly cross-sectional data and point-in-time images of patients’ lives rather than assessing the possible cumulative disability over a patient’s lifetime. However, social and economic outcomes indicate there are likely negative impacts that accumulate over time. To capture the cumulative effect of psoriasis and its associated co-morbidities and stigma over a patient’s life course, we propose the concept of ‘Cumulative Life Course Impairment’ (CLCI). CLCI results from an interaction between (A) the burden of stigmatization, and physical and psychological co-morbidities and (B) coping strategies and external factors. Several key aspects of the CLCI concept are supported by data similar to that used in health-related quality of life assessments. Future research should focus on (i) establishing key components of CLCI and determining the mechanisms of impairment through longitudinal or retrospective case–control studies, and (ii) assessing factors that put patients at increased risk of developing CLCI. In the future, this concept may lead to a better understanding of the overall impact of psoriasis, help identify more vulnerable patients, and facilitate more appropriate treatment decisions or earlier referrals. To our knowledge, this is a first attempt to apply and develop concepts from ‘Life Course Epidemiology’ to psoriasis research. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article on the impact of the major life changing decisions (MLCDs) to the cumulative impairment of disease.