HER2-low expression in patients with advanced or metastatic solid tumors.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2)-low is a newly defined category with HER2 1+ or 2+ expression by immunohistochemistry (IHC) and lack of HER2 gene amplification measured by in situ hybridization (ISH). Much remains unknown about the HER2-low status across tumor types and changes in HER2 status between primary and metastatic samples. PATIENTS AND METHODS: HER2 expression by IHC was evaluated in 4701 patients with solid tumors. We have evaluated the HER2 expression by IHC and amplification by ISH in paired breast and gastric/gastroesophageal (GEJ) primary and metastatic samples. HER2 expression was correlated with ERBB2 genomic alterations evaluated by next-generation sequencing (NGS) in non-breast, non-gastric/GEJ samples. RESULTS: HER2 expression (HER2 IHC 1-3+) was found in half (49.8%) of the cancers, with HER2-low (1 or 2+) found in many tumor types: 47.1% in breast, 34.6% in gastric/GEJ, 50.0% in salivary gland, 46.9% in lung, 46.5% in endometrial, 46% in urothelial, and 45.5% of gallbladder cancers. The concordance evaluation of HER2 expression between primary and metastatic breast cancer samples showed that HER2 3+ remained unchanged in 87.1% with a strong agreement between primary and metastatic samples, with a weighted kappa (Κ) of 0.85 (95% confidence interval 0.79-0.91). ERBB2 alterations were identified in 117 (7.5%) patients with non-breast, non-gastric/GEJ solid tumors who had NGS testing. Of 1436 patients without ERBB2 alterations, 512 (35.7%) showed any level HER2 expression by IHC. CONCLUSION: Our results show that HER2-low expression is frequently found across tumor types. These findings suggest that many patients with HER2-low solid tumors might benefit from HER2-targeted therapies.

Dosimetric feasibility of hippocampal avoidance whole brain radiotherapy with an MRI-guided linear accelerator.

PURPOSE/OBJECTIVE(S): Whole brain radiotherapy with hippocampal avoidance (HA-WBRT) is a technique utilized to treat metastatic brain disease while preserving memory and neurocognitive function. We hypothesized that the treatment planning and delivery of HA-WBRT plans is feasible with an MRI-guided linear accelerator (linac) and compared plan results with clinical non-MRI-guided C-Arm linac plans. MATERIALS/METHODS: Twelve HA-WBRT patients treated on a non-MRI-guided C-Arm linac were selected for retrospective analysis. Treatment plans were developed using a 0.35T MRI-guided linac system for comparison to clinical plans. Treatment planning goals were defined as provided in the Phase II Trial NRG CC001. MRI-guided radiotherapy (MRgRT) treatment plans were developed by a dosimetrist and compared with clinical plans. quality assurance (QA) plans were generated and delivered on the MRI-guided linac to a cylindrical diode detector array. Planning target volume (PTV) coverage was normalized to ∼95% to provide a control point for comparison of dose to the organs at risk. RESULTS: MRgRT plans were deliverable and met all clinical goals. Mean values demonstrated that the clinical plans were less heterogeneous than MRgRT plans with mean PTV V37.5 Gy of 0.00% and 0.03% (p = 0.013), respectively. Average hippocampi maximum doses were 14.19 ± 1.29 Gy and 15.00 ± 1.51 Gy, respectively. The gamma analysis comparing planned and measured doses resulted in a mean of 99.9% ± 0.12% of passing points (3%/2mm criteria). MRgRT plans had an average of 38.33 beams with average total delivery time and beam-on time of 13.7 (11.2-17.5) min and 4.1 (3.2-5.4) min, respectively. Clinical plan delivery times ranged from 3 to 7 min depending on the number of noncoplanar arcs. Planning time between the clinical and MRgRT plans was comparable. CONCLUSION: This study demonstrates that HA-WBRT can be treated using an MRI-guided linear accelerator with comparable treatment plan quality and delivery accuracy.

Dimethyl fumarate modulates the Treg-Th17 cell axis in patients with psoriasis.

BACKGROUND: Dimethyl fumarate (DMF) is the active ingredient of Skilarence™ and Tecfidera™, which are used for the treatment of psoriasis and multiple sclerosis, respectively. Various immunomodulatory mechanisms of action have been identified for DMF; however, it is still unclear what effects DMF exerts in vivo in patients with psoriasis. OBJECTIVES: In this study we examined the effects of DMF, both in vivo and in vitro, on T cells, which play a key role in the pathogenesis of psoriasis. METHODS: The frequency of T-cell subsets was examined by flow cytometry in untreated patients with psoriasis or those treated with DMF. The effects of DMF in vitro on T-cell survival, activation and proliferation, and cell-surface thiols were assessed by flow cytometry. RESULTS: In patients with psoriasis treated with DMF we observed an increase in the frequency of T regulatory (Treg) cells and a decrease in T helper (Th)17 lineage cells and the associated cytokines interleukin-17, interleukin-22 and granulocyte-macrophage colony-stimulating factor. T cells cultured in vitro with DMF exhibited reduced viability, and inhibition of activation and proliferation in response to stimulation due to the oxidative effects of DMF. However, the frequency of Treg cells increased in the presence of DMF due to their heightened ability to resist DMF-induced oxidative stress. CONCLUSIONS: DMF enhanced the ratio of Treg cells to Th17 cells in patients with psoriasis, in patients with multiple sclerosis and in vitro. Furthermore, our data suggest that this is at least in part as a result of the differential effects of DMF on Treg cells compared with conventional T cells.

Improvement in Hidradenitis Suppurativa and quality of life in patients treated with adalimumab: Real-world results from the HARMONY Study.

BACKGROUND: Hidradenitis suppurativa (HS), a chronic, recurrent, debilitating skin disease, is characterized by painful, inflammatory, subcutaneous lesions of the axilla, inguinal and anogenital regions. Overall prevalence of HS is ˜1%, and the impact of disease on patient quality of life (QoL) and healthcare resource utilization (HRU) is high. OBJECTIVES: To estimate the real-world effectiveness of adalimumab (Humira®) treatment in patients with moderate-to-severe HS on disease severity, pain, QoL, work productivity and HRU. METHODS: HARMONY (Effectiveness of Adalimumab in Moderate to Severe HidrAdenitis SuppuRativa Patients - a Multi-cOuNtry studY in Real Life Setting) is a multicentre, postmarketing observational study in adult patients with moderate-to-severe HS. Disease severity and QoL parameters were evaluated using validated measures at 12-week intervals over 52 weeks of treatment. The primary endpoint was the proportion of patients achieving a Hidradenitis Suppurativa Clinical Response (HiSCR: ≥50% reduction in abscess and inflammatory nodule count, with no increase in abscess and draining fistula counts relative to baseline) at 12 weeks. Secondary endpoints were HiSCR at 24, 36 and 52 weeks and changes in QoL parameters and work productivity assessments. Analyses were conducted using as-observed data. RESULTS: The proportion of patients reaching the primary HiSCR endpoint was 70.2% (n = 132/188 enrolled) and remained ≥70% until study completion. There were statistically significant (P < 0.0001) reductions in worst and average skin pain. All of the QoL measures evaluated improved significantly (P < 0.0001) by 12 weeks of adalimumab treatment, as did work productivity assessments (P < 0.05), and there was a ˜50% decrease in HRU between baseline and week 52. Adalimumab was well tolerated. CONCLUSIONS: In this real-world setting, adalimumab treatment of moderate-to-severe HS resulted in decreased disease severity and improvements in QoL and productivity. Response to adalimumab was rapid (within 12 weeks) and sustained (52 weeks). No unexpected safety signals were reported.

Secukinumab for patients failing previous tumour necrosis factor-α inhibitor therapy: results of a randomized open-label study (SIGNATURE).

BACKGROUND: Efficacy data on therapies for patients with psoriasis who have failed tumour necrosis factor (TNF)-α inhibitor therapy is limited. OBJECTIVES: To determine the effectiveness and tolerability of secukinumab, an interleukin (IL)-17A inhibitor, in patients with moderate/severe chronic plaque psoriasis with documented efficacy failure of TNF-α inhibitor therapy (SIGNATURE study). METHODS: This was a randomized, open-label, noncomparator study in 53 dermatology centres in the U.K. and Republic of Ireland. Patients were randomized 1 : 1 to receive secukinumab 300 mg or 150 mg subcutaneously every week for 4 weeks, then 4-weekly thereafter. Patients were stratified by their prior efficacy failure with TNF-α inhibitors. Only patients who started and stayed on the same dose at each time point were included for efficacy assessments. RESULTS: In total, 233 patients were analysed. The primary end point was met, with a statistically significant improvement in response rates [75% reduction in Psoriasis Area and Severity Index (PASI 75)] from baseline to week 16 in both secukinumab 300 mg and 150 mg dose groups [77 of 118 patients (65·3%) and 51 of 115 patients (44·3%), respectively; P < 0·0001]. After 72 weeks, in patients starting and remaining on 300 mg, 77% (54 of 70) achieved PASI 75. Improvements in Dermatology Life Quality Index from baseline to week 16 occurred and were maintained up to 72 weeks. The safety profile was generally consistent with previous secukinumab studies, although a higher incidence of some adverse events (e.g. candida infections) was observed. CONCLUSIONS: This study provides evidence of efficacy and safety of secukinumab for treatment of patients with psoriasis who failed prior TNF-α inhibitor therapy. This study represents a 'real-world' population, providing reassurance that secukinumab is a treatment option in this difficult-to-treat population. What's already known about this topic? Conventional systemic nonbiological and tumour necrosis factor (TNF)-α inhibitor therapies for plaque psoriasis have not fully met patients' needs. There is a lack of data to support the treatment pathways for patients with psoriasis who have inadequate responses to TNF-α inhibitor therapy. Secukinumab, a recombinant high-affinity fully human monoclonal anti-human interleukin-17A antibody of the IgG1/κ-class, has shown excellent safety and efficacy in the treatment of moderate-to-severe psoriasis. What does this study add? This is the first study evaluating treatment with biologics after prior efficacy failure of TNF-α inhibitor therapy as defined by the U.K. National Institute for Health and Care Excellence criteria. Secukinumab is an effective treatment in this difficult-to-treat patient population. This study provides important practical information for clinicians managing psoriasis. Adverse events were consistent with the phase III programme for secukinumab, although some adverse events, e.g. candida, were increased.

Investigation of the skin microbiome: swabs vs. biopsies.

BACKGROUND: Human skin is populated by diverse bacteria and there is increasing evidence that resident bacteria play a key role initiating immune responses in cutaneous diseases such as atopic dermatitis, psoriasis and hidradenitis suppurativa. Bacteria are present at all layers of the skin but many studies have relied on swabs to profile the skin microbiota. OBJECTIVES: As the pathogenesis of many skin conditions is dermal, we wanted to compare the microbiota obtained in swabs (surface) and biopsies (dermis). METHODS: Using 16S rRNA gene sequencing we established the microbial profiles of skin swabs and skin biopsies in 16 patients. RESULTS: We found differences in both diversity and taxonomic composition of the microbiome obtained from swabs and biopsies of the same individual. Several taxa were found to be more abundant in the swabs, which displayed significantly higher community richness, but Clostridiales and Bacteroidetes were significantly enriched in the biopsies. Most published research on cutaneous microbiota has been based on skin swabs, which represent the surface of the skin. CONCLUSIONS: Our study demonstrated a clear difference between the microbiome observed from skin swabs and skin biopsies. These findings may be highly relevant in disorders such as psoriasis where pathogenesis arises in the dermis. What's already known about this topic? 16S RNA gene sequencing has facilitated study of the skin microbiome. Several studies have sequenced the microbiome sampled by skin swabs. What does this study add? The microbiome data obtained using swabs and biopsies were different. Diseases that are predominantly dermal should be studied using both swabs and biopsies.

Reversibility of alexithymia with effective treatment of moderate-to-severe psoriasis: longitudinal data from EPIDEPSO.

BACKGROUND: Alexithymia refers to difficulty in identifying and expressing emotions. Alexithymia is associated with high burden of disease in patients with psoriasis. OBJECTIVES: To investigate whether alexithymia was reversible in patients with psoriasis following real-life therapeutic intervention. METHODS: The Epidemiological Study in Patients with Recently Diagnosed Psoriasis (EPIDEPSO; NCT01964443) was a 1-year multicentre observational study investigating the prevalence of alexithymia and other psychosocial comorbidities in patients with psoriasis with ≤ 10 years' disease duration and eligible for systemic treatment. Alexithymia was assessed using the Toronto Alexithymia Scale (TAS-20) at baseline, 6 months and 1 year. RESULTS: There was a statistically significant decrease in the prevalence of alexithymia in the follow-up cohort, from 26·7% at baseline to 21·2% at 6 months and 18·8% at 1 year. More than half of the patients (n = 77, 53·8%) who were alexithymic at baseline experienced reversion of their alexithymia. Reversion of alexithymia was higher in patients who reached a high level of disease control, defined as ≥ 75% or ≥ 90% improvement in Psoriasis Area and Severity Index. Reversion of alexithymia was associated with dramatic improvement in quality of life, anxiety and depression. Moreover, hazardous alcohol use, highly prevalent in patients with alexithymia, was reduced almost threefold at 1 year. CONCLUSIONS: Alexithymia and associated high disease burden may be reversible in patients with effective treatment of psoriasis. Proactive recognition of patients who are unable to identify and express their feelings is important.

Validation and psychometric evaluation of a brief screening questionnaire for psychological distress in patients with psoriasis.

BACKGROUND: Patients with psoriasis are at risk of a co-morbid diagnosis of depression and/or anxiety. It is therefore essential for dermatologists to have valid and effective instruments that can screen and monitor depression and anxiety symptoms in psoriasis patients. OBJECTIVE: The aim of this study was to validate the Mental Health Inventory (MHI-5) as a brief measure that can be used to evaluate psychological distress related to anxiety and depression in psoriasis patients. METHODS: The sample included 76 adult dermatological outpatients diagnosed with psoriasis. Participants completed the MHI-5, the Hospital Anxiety and Depression Scale (HADS) and six subscales of the Self-Compassion Scale (SCS). Confirmatory factor analysis (CFA) was applied to examine the factor structure of MHI-5. Convergent validity was examined by applying correlations among all measures. Discriminant validity was examined by applying hierarchical regression models. Reliability was examined by calculating Cronbach's alpha coefficient. RESULTS: Confirmatory factor analysis showed that the proposed one-factor model has a good fit to the data. The MHI-5 demonstrated satisfactory convergent validity by yielding significant moderate to strong correlations with the HADS and with the positive and negative subscales of the SCS. Discriminant validity was also evident with being at risk of anxiety predicting MHI-5 scores above and beyond the effect of gender and age. Hierarchical regressions were not performed because a very small number of participants (n = 3) were classified at risk of depression. The MHI-5 showed high internal consistency (α = 0.84). CONCLUSION: This investigation provided evidence that MHI-5 is a reliable and valid instrument that can be used to effectively capture psychological distress in psoriasis patients.

Hidradenitis suppurativa/acne inversa: a practical framework for treatment optimization - systematic review and recommendations from the HS ALLIANCE working group.

Hidradenitis suppurativa (HS)/acne inversa is a debilitating chronic disease that remains poorly understood and difficult to manage. Clinical practice is variable, and there is a need for international, evidence-based and easily applicable consensus on HS management. We report here the findings of a systematic literature review, which were subsequently used as a basis for the development of international consensus recommendations for the management of patients with HS. A systematic literature review was performed for each of nine clinical questions in HS (defined by an expert steering committee), covering comorbidity assessment, therapy (medical, surgical and combinations) and response to treatment. Included articles underwent data extraction and were graded according to the Oxford Centre for Evidence-based Medicine criteria. Evidence-based recommendations were then drafted, refined and voted upon, using a modified Delphi process. Overall, 5310 articles were screened, 171 articles were analysed, and 65 were used to derive recommendations. These articles included six randomized controlled trials plus cohort studies and case series. The highest level of evidence concerned dosing recommendations for topical clindamycin in mild disease (with systemic tetracyclines for more frequent/widespread lesions) and biologic therapy (especially adalimumab) as second-line agents (following conventional therapy failure). Good-quality evidence was available for the hidradenitis suppurativa clinical response (HiSCR) as a dichotomous outcome measure in inflammatory areas under treatment. Lower-level evidence supported recommendations for topical triclosan and oral zinc in mild-to-moderate HS, systemic clindamycin and rifampicin in moderate HS and intravenous ertapenem in selected patients with more severe disease. Intralesional or systemic steroids may also be considered. Local surgical excision is suggested for mild-to-moderate HS, with wide excision for more extensive disease. Despite a paucity of good-quality data on management decisions in HS, this systematic review has enabled the development of robust and easily applicable clinical recommendations for international physicians based on graded evidence.

Effective modulation of intramolecular ferromagnetic interaction of diradicals by functionalization of cross-conjugated coupler.

Cross-conjugated molecules are an interesting class of conjugated systems possessing a spatially separated HOMO and LUMO. Most previous studies have taken advantage of this property by using it in organic semiconductor applications. Herein, we undertake a new investigation on the use of this type of molecule, in particular benzo[1,2-d;4,5-d']bisoxazole (BBO), as a coupler for organic diradicals. BBO has two sites available for adding a substituent and a spin center (SC) which are along its 4,8- and 2,6-axes. Functionalizations using electron donating (ED) and electron withdrawing (EW) groups were imposed to tune its FMOs and it was found that the longer 2,6-axis is an ideal site with a broader LUMO range via substituent effects. Diradicalization of these BBOs using nitronyl nitroxide (NN) and nitroxide (NO) as SCs was done using the remaining available axis. The calculated J values are linearly dependent on the LUMO energy of the coupler, but with 4,8-NH2-2,6-SC as an outlier. This exceptional case is related to 4,8-NH2-2,6-SC having the lowest BBO-NN dihedral angle. Moreover, the diradicals 4,8-X-2,6-SC (with X = H, NH2, CH3) have higher J values than 2,6-X-4,8-SC (with X = H, NH2, CH3), which is counterintuitive because the latter have a shorter coupling path. These diradicals are positioned to the right of the intersection of their trend lines, which implies that diradicals with LUMO values to the right of this intersection have the tendency to attain J values that are higher than those diradicals with a shorter coupling path. 4,8-NH2-2,6-SC even surpasses the projected JMax values which we associate with the highest attainable J values due to LUMO tuning via substituent effects. These results provide useful insights, especially into the interplay between the LUMO and the dihedral angle and how these affect magnetism in diradicals. In conclusion, we found that BBO can be a good candidate as an effective coupler for diradicals with tunable J values via incorporation of ED and EW groups. This first approach to studying the application of cross-conjugated molecules as couplers also paves the way for new candidates for the development of more effective diradical systems.

A cross-sectional epidemiological study of hidradenitis suppurativa in an Irish population (SHIP).

BACKGROUND: Hidradenitis suppurativa (HS), a chronic inflammatory disease that affects apocrine gland-bearing skin, has a significant impact on patients' quality of life. Estimates of the epidemiologic prevalence of HS are highly variable, and clinical data on disease characteristics and patient burden of disease remain limited. OBJECTIVE: The primary objective of this study was to determine the number of patients with HS attending dermatology clinics in a hospital setting in Ireland (within a 6-month time period). Secondary objectives included the assessment of disease characteristics and the collection of patient responses on disease burden and work productivity. METHODS: This was an epidemiologic, non-interventional, cross-sectional study across four dermatology clinics in Ireland over a 6-month time period. The disease prevalence was estimated by calculating the percentage of total patients with a diagnosis of HS (the primary population) across the selected sites. Secondary analyses were performed using the full analysis set, which consisted of eligible adults (≥18 years of age) from the primary population who provided informed consent. Data from these analyses are presented as descriptive summary statistics, with the use of an analysis of covariance for continuous endpoints. RESULTS: The prevalence of HS across the four selected sites was estimated at 1.4% (95% CI, 1.24-1.62). One hundred and fifty eligible patients comprised the full analysis set. The majority of participants were white (95.3%), female (70.0%), cigarette smokers (56.0%) and overweight or obese (body mass index ≥25 kg/m2 , 81.8%). Most patients for whom data were available presented with Hurley stage II (50.4%), and more than a third of the full analysis set had a relative with HS (34.7%). Questionnaire responses revealed a profound impact on quality of life, including diminished work productivity and various psychological comorbidities. CONCLUSION: This study offers insight into the clinical features and disease burden of hidradenitis suppurativa in an Irish population.

Clinical use of dimethyl fumarate in moderate-to-severe plaque-type psoriasis: a European expert consensus.

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.

Natural killer cells from psoriasis vulgaris patients have reduced levels of cytotoxicity associated degranulation and cytokine production.

Psoriasis vulgaris is a chronic inflammatory disease of the skin with a strong genetic component and immune system involvement. Although some evidence suggests that Natural Killer (NK) cells may play a part in psoriasis, their role is relatively unstudied and results are controversial. In this current study, NK cells from psoriasis patients exhibited reduced degranulation and produced lower levels of the pro-inflammatory cytokines IFN-γ and TNF-α. Further investigation found that NK cells from psoriasis patients and healthy controls expressed similar levels of activation markers, NK cell receptors and apoptosis-inducing molecules. In addition, comparable levels of several cytokines important in NK cell biology were found in the serum of psoriasis patients and healthy controls. Genotyping analysis revealed that HLA-C2, which provides a ligand for killer-cell immunoglobulin-like receptors (KIR) expressed by NK cells, was strongly associated with psoriasis susceptibility. However, no link between the KIR genes themselves and disease was found.

Structural "δ Doping" to Control Local Magnetization in Isovalent Oxide Heterostructures.

Modulation and δ-doping strategies, in which atomically thin layers of charged dopants are precisely deposited within a heterostructure, have played enabling roles in the discovery of new physical behavior in electronic materials. Here, we demonstrate a purely structural "δ-doping" strategy in complex oxide heterostructures, in which atomically thin manganite layers are inserted into an isovalent manganite host, thereby modifying the local rotations of corner-connected MnO_{6} octahedra. Combining scanning transmission electron microscopy, polarized neutron reflectometry, and density functional theory, we reveal how local magnetic exchange interactions are enhanced within the spatially confined regions of suppressed octahedral rotations. The combined experimental and theoretical results illustrate the potential to utilize noncharge-based approaches to "doping" in order to enhance or suppress functional properties within spatially confined regions of oxide heterostructures.

The treatment of hidradenitis suppurativa with the glucagon-like peptide-1 agonist liraglutide.

Hidradenitis suppurativa (HS) is a cutaneous disease associated with systemic inflammation, obesity and metabolic syndrome. Effective treatment options are limited. The antidiabetic agents, incretins, have been used successfully to treat psoriasis - a disease also associated with metabolic syndrome. We report the use of liraglutide, a glucagon-like peptide-1 agonist, in a patient with HS, leading to subsequent weight loss and improvement in disease control. To our knowledge, this is the first report of liraglutide used in the treatment of HS.

Identification of factors that may influence the selection of first-line biological therapy for people with psoriasis: a prospective, multicentre cohort study.

BACKGROUND: The Psoriasis Stratification to Optimise Relevant Therapy (PSORT) consortium has a collective aim to develop a prescribing algorithm to help stratify eligible patients with psoriasis to the most appropriate biological treatment. To facilitate the adoption of a stratified approach, it is necessary to first understand the factors driving the choice of first-line biological therapy. OBJECTIVES: To identify and quantify factors that influence the selection of the first-line biological therapy for people with psoriasis. METHODS: Multinomial logistic regression was used to determine the factors that influenced the probability of treatment selection, using data from the British Association of Dermatologists Biologic Interventions Register from January 2012 to December 2015. Sensitivity analyses were performed to assess the robustness of the findings to key assumptions. RESULTS: The main analysis was based on a dataset comprising 3040 people with psoriasis. The identified factors affecting first-line biological selection within the available therapies were: presence of psoriatic arthritis; patient weight; employment status; country of registration; and baseline disease severity. Importantly, the analysis showed a general shift in prescribing behaviour over time. These results were robust to sensitivity analysis. CONCLUSIONS: This study offers important insights into the factors influencing current prescribing practice for first-line biological therapies for people with psoriasis. It provides baseline data to inform the evaluation of future potential changes that may affect prescribing behaviour, such as stratified medicine.

Prevalence of alexithymia in patients with psoriasis and its association with disease burden: a multicentre observational study.

BACKGROUND: Single-centre studies show that alexithymia, defined as difficulty in recognizing and describing emotions, is more prevalent among patients with psoriasis than in the general population. However, its prevalence and the consequences of the association between alexithymia and psoriasis are unclear. OBJECTIVES: The primary objective of this study was to determine the prevalence of alexithymia, as defined by a score ≥ 61 in the 20-item Toronto Alexithymia Scale, in a large sample of patients who had plaque psoriasis for ≤ 10 years and were eligible for phototherapy or systemic treatment. The secondary objectives were to investigate the relationship between alexithymia and the clinical and psychological aspects of psoriasis. METHODS: Data were collected in the framework of an observational, multicentre, international study, the EPidemiological Study In Patients With Recently DiagnosEd PSOriasis (EPIDEPSO), aiming at investigating the prevalence of alexithymia and other psychosocial comorbidities in patients with psoriasis of ≤ 10 years' disease duration. RESULTS: The prevalence of alexithymia within a cohort of 670 patients was 24·8% (95% confidence interval 21·7-28·2). Patients with alexithymia had a higher burden of psoriasis, including significant impairment of quality of life, higher levels of anxiety and depression, a higher risk of alcohol dependency and impairment of work productivity, compared with patients without alexithymia. CONCLUSIONS: It is important to identify alexithymic patients with psoriasis in clinical practice as they experience a higher disease burden and have a lower ability to express their feelings.

Renal dysfunction in patients taking fumaric acid esters - a retrospective cross-sectional study.

BACKGROUND: Fumaric acid esters (FAE) have been used for over 30 years in the management of psoriasis. There have been a number of case reports linking the use of FAE with nephrotoxicity, including acute renal injury and Fanconi syndrome. However, one large multicentre retrospective trial showed no evidence of renal dysfunction with FAE. OBJECTIVES/AIMS: The aim of this study was to determine the number of patients in our institution being treated with FAE who developed significant proteinuria or renal dysfunction. METHODS: This was a single-centre retrospective study assessing all patients on FAE who attended for follow-up during an 18-week period between February and June 2015. Demographics, comorbidities, duration and dose of treatment with FAE, proteinuria, renal function and other biochemical serum abnormalities were recorded. RESULTS: One hundred and twenty-seven patients were included in the study. Eighty-two patients had proteinuria detected at some stage during treatment with FAE, and 18 of these had persistent proteinuria (positive in at least three consecutive specimens, 12 weeks apart). Six patients (five female) developed proximal tubular dysfunction (PTD). The risk factors for the development of PTD appear to be lower bodyweight (P = 0.03), higher dose per weight (P = 0.03) and longer duration of treatment (P = 0.03). Renal dysfunction improved on discontinuation or dose reduction in FAE. CONCLUSION: Fumaric acid esters are frequently associated with transient or persistent proteinuria. Significant renal dysfunction is rare and usually reversible on dose reduction or discontinuation of FAE. This study highlights the importance of screening for proteinuria. Higher doses per weight of treatment and longer duration of FAE therapy are likely risk factors for PTD.