Efficacy of spesolimab for the treatment of generalized pustular psoriasis flares across pre-specified patient subgroups in the Effisayil 1 study.

Effisayil 1 was a multicentre, randomized, double-blind, placebo-controlled study of the anti-interleukin (IL)-36 receptor monoclonal antibody, spesolimab, in patients presenting with a generalized pustular psoriasis (GPP) flare. Previously published data from this study revealed that within 1 week, rapid pustular and skin clearance were observed in patients receiving spesolimab versus placebo. In this pre-specified subgroup analysis, the efficacy of spesolimab was evaluated according to patient demographic and clinical characteristics at baseline in patients receiving spesolimab (n = 35) or placebo (n = 18) on Day 1. Efficacy was by assessed by achievement of primary endpoint (Generalized Pustular Psoriasis Physician Global Assessment [GPPGA] pustulation subscore of 0 at Week 1) and key secondary endpoint (GPPGA total score of 0 or 1 at Week 1). Safety was assessed at Week 1. Spesolimab was found to be efficacious and had a consistent and favourable safety profile in patients presenting with a GPP flare, regardless of patient demographics and clinical characteristics at baseline.

Long-term safety of certolizumab pegol in plaque psoriasis: pooled analysis over 3 years from three phase III, randomized, placebo-controlled studies.

BACKGROUND: Certolizumab pegol (CZP) is an Fc-free, PEGylated anti-tumour necrosis factor biologic. OBJECTIVES: To report 3-year safety data from three phase III trials of CZP in adults with plaque psoriasis. METHODS: Data were pooled from CIMPASI-1 (NCT02326298), CIMPASI-2 (NCT02326272) and CIMPACT (NCT02346240). Included patients had moderate-to-severe plaque psoriasis of ≥ 6 months' duration; had been randomized to CZP 200 mg every 2 weeks (Q2W) (400 mg at weeks 0, 2 and 4) or CZP 400 mg Q2W; and had received at least one dose of CZP with up to 144 weeks of exposure. Treatment-emergent adverse events (TEAEs) were classified using MedDRA v18·1. Reported incidence rates (IRs) are incidence of new cases per 100 patient-years (PY). RESULTS: Over 144 weeks, 995 patients received at least one dose of CZP (exposure: 2231·3 PY); 731 and 728 received at least one dose of CZP 200 mg Q2W (1211·4 PY) and/or 400 mg Q2W (1019·9 PY), respectively. The IR [95% confidence interval (CI)] of TEAEs was 144·9 (135·3-155·0) for all patients, 134·1 (123·2-145·7) for CZP 200 mg Q2W and 158·3 (145·5-171·9) for CZP 400 mg Q2W. The IR (95% CI) of serious TEAEs for all patients was 7·5 (6·4-8·8); the IRs were 6·7 (5·2-8·3) and 8·7 (6·9-10·8) for CZP 200 mg and 400 mg Q2W, respectively. Overall, 3·2% of patients reported serious infections (2·2% within each of the CZP 200 and 400 mg Q2W groups). Overall, there was one case of active tuberculosis, 16 malignancies in 14 patients and seven deaths (two considered treatment-related). The cumulative IR of TEAEs did not increase over time. CONCLUSIONS: No new safety signals were identified compared with previously reported data. Risk did not increase with longer or higher CZP exposure.

Psoriasis severity: commonly used clinical thresholds may not adequately convey patient impact.

BACKGROUND: Psoriasis severity is usually evaluated using quantitative and qualitative measures, including per cent body surface area (BSA) involvement, the Psoriasis Area and Severity Index (PASI) and the Dermatology Life Quality Index (DLQI), a patient-reported questionnaire. However, standardized definitions for psoriasis severity categories have not been well established. A PASI of 10 or 12 has remained the minimal severity threshold defining eligibility for psoriasis treatments. In the present study, the validity of this cut-off was re-evaluated in the context of quality of life. OBJECTIVE: To determine whether the thresholds commonly used to define moderate psoriasis (PASI of 10-12 and BSA of 10) are supported by patient-reported DLQI data. METHODS: A systematic review of randomized controlled trials that enrolled mild or moderate patients published between January 2000 and June 2017 was used to assess correlations between provider and patient-generated severity at baseline. RESULTS: For subject groups with high impact on quality of life (DLQI > 10), the mean weighted BSA was 7.6 (Range: 7.1-8.4) and the mean weighted DLQI was 11 (Range: 10.2-12.2). Similarly, the mean weighted PASI for patients with DLQI > 10 was 8.7 (Range: 7.1-10.1) and the mean weighted DLQI was 10.9 (Range: 10.1-12.2). CONCLUSION: Patients with PASI or BSA scores less than 10 can have major quality of life impairment. In general, the objective measures of BSA and PASI alone, when excluding DLQI, may not fully capture the impact of disease severity.

Frailty screening in dermato-oncology practice: a modified Delphi study and a systematic review of the literature.

BACKGROUND: Appropriate management and prevention of both under- and overtreatment in older skin cancer patients can be challenging. It could be helpful to incorporate frailty screening in dermato-oncology care, since frailty is associated with adverse health outcomes. OBJECTIVES: This study aimed to identify and prioritize the requirements a frailty screening tool (FST) should fulfil in dermato-oncology practice and to select the best existing FST(s) for this purpose. METHODS: A modified two-round Delphi procedure was performed among 50 Italian and Dutch specialists and patients to review and prioritize a list of potential FST requirements, using a 5-point Likert scale. Consensus was defined as a mean score of ≥4.0. A systematic literature search was performed to identify existing multidomain FSTs, which were then assessed on the requirements resulting from the modified Delphi procedure. RESULTS: Consensus was achieved on evaluation of comorbidities (4.3 ± 0.7), polypharmacy (4.0 ± 0.9) and cognition (4.1 ± 0.8). The FST should have appropriate measurement properties (4.0 ± 1.0), be quickly executed (4.2 ± 0.7), clinically relevant (4.3 ± 0.7), and both easily understandable (4.1 ± 1.2) and interpretable (4.3 ± 0.7). Of the 26 identified FSTs, four evaluated the content-related domains: the Geriatric-8 (G8), the modified Geriatric-8 (mG8), the Groningen Frailty Indicator (GFI) and the Senior Adult Oncology Program 2 (SAOP2) screening tool. Of these, the G8 was the most extensively studied FST, with the best psychometric properties and execution within 5 min. CONCLUSIONS: The G8 appears the most suitable FST for assessing frailty in older adults with skin cancer, although clinical studies assessing its use in a dermato-oncology population are needed to further assess whether or not frailty in this particular patient group is associated with relevant outcomes (e.g. complications and mortality), as seen in previous studies in other medical fields.

Phototherapy in the perspective of the chronicity of psoriasis.

According to the guidelines for the treatment of psoriasis, phototherapy is given in courses of UVB exposure starting at 50-70% of the minimal erythema dose, MED, with subsequently incremental dosages, but keeping erythemal skin reactions to a minimum by restraining the dosages when necessary. In this review, this classical principle of short-term near erythematogenic UVB therapy without further UVB maintenance therapy is challenged as it is evidently not optimal for psoriasis as a chronic condition. There is old experimental evidence supplemented with growing knowledge on the mode of action of phototherapy and more recent data on low-level UVB regimens as maintenance therapy that should urge us to revisit our guidelines on phototherapy to address psoriasis for what it is: a chronic condition.

Quality of life outcomes in adults with moderate-to-severe plaque psoriasis treated with dimethylfumarate (DMF): a post hoc analysis of the BRIDGE study.

BACKGROUND: Psoriasis is a chronic inflammatory skin disease associated with quality of life (QoL) impairment. BRIDGE was a randomized, double-blind, phase III study comparing the efficacy and safety of dimethylfumarate (DMF) with a fixed combination of fumaric acid esters (FAE) or placebo for the treatment of moderate-to-severe psoriasis. OBJECTIVES: This post hoc analysis investigated treatment effect on QoL overall and by patient subgroups categorized by disease severity. Week 8 efficacy responses were also investigated as possible predictors of Week 16 Dermatology Life Quality Index (DLQI) outcomes. METHODS: Patients were randomized to receive a maximum daily dose of 720 mg of DMF, FAE (gradual up-titration) or placebo for 16 weeks. Psoriasis Area Severity Index, Body Surface Area, Physician's Global Assessment and DLQI were assessed at baseline, Weeks 8 and 16. DLQI 0-1 indicated 'no effect on patient life'. Associations between baseline severity, Week 16 DLQI and Week 8 efficacy (as observed cases) were also examined. RESULTS: At baseline, 671 patients were included in the full analysis set (267 randomized to DMF, 273 to FAE and 131 to placebo). DMF was superior to placebo (P < 0.001) and not significantly different to FAE regarding Week 16 DLQI outcomes (P > 0.05). Baseline disease severity did not impact DLQI outcomes at Week 16. In DMF- and FAE-treated patients, Week 8 PASI 50/75 responders reported better DLQI responses at Week 16 vs non-responders (P < 0.05). Week 8 PASI ≤ 3 and/or PGA 0-1 responders were also more likely to report DLQI 0-1 at Week 16 vs non-responders (P < 0.05). CONCLUSION: Dimethylfumarate significantly improved DLQI outcomes vs. placebo and was not affected by baseline disease severity. Efficacy responses (PASI 50/75, PASI ≤3 and PGA 0-1) as early as Week 8 were predictive of QoL outcomes at Week 16 in DMF- and FAE-treated patients.

Benefit-risk profile of tofacitinib in patients with moderate-to-severe chronic plaque psoriasis: pooled analysis across six clinical trials.

BACKGROUND: Although existing psoriasis treatments are effective and well tolerated in many patients, there is still a need for new effective targeted treatment options. Tofacitinib is an oral Janus kinase inhibitor that has been investigated in patients with moderate-to-severe chronic plaque psoriasis. OBJECTIVES: To consider the benefits and risks of tofacitinib in patients with moderate-to-severe psoriasis. METHODS: Data were pooled from one phase II, four phase III and one long-term extension study comprising 5204 patient-years of tofacitinib treatment. Efficacy end points included patients achieving Physician's Global Assessments of 'clear' or 'almost clear', ≥ 75% and ≥ 90% reduction in Psoriasis Area and Severity Index (coprimary end points) and improvements in Dermatology Life Quality Index score, Hospital Anxiety and Depression Scale depression score and Itch Severity Item score, at weeks 16 and 52. Safety data were summarized for 3 years of tofacitinib exposure. RESULTS: Tofacitinib 5 and 10 mg twice daily (BID) showed superiority over placebo for all efficacy end points at week 16, with response maintained for 52 weeks of continued treatment. Tofacitinib improved patients' quality of life and was well tolerated. Rates of safety events of interest (except herpes zoster) were similar to those in the published literature and healthcare databases for other systemic psoriasis therapies. Tofacitinib 10 mg BID demonstrated greater efficacy than 5 mg BID. CONCLUSIONS: Tofacitinib has a benefit-risk profile in moderate-to-severe psoriasis consistent with that of other systemic treatments.

Severity, heterogeneity and systemic inflammation in psoriasis.

Psoriasis may express as active severe disease or as mild stable disease. In particular, patients with active severe disease present systemic involvement, including comorbidities and increased values of parameters reflecting an active state of innate immunity. In contrast, patients with mild stable disease show a dominancy of acquired immunity. In this review article, we report the clinical aspects of disease manifestations of both active and quiescent psoriasis as well as the immunological aspects, as well as the impact on antimicrobial resistance. The activity of psoriasis is not captured in the present outcome measures for severity assessment. The present review suggests that incorporating disease activity may be important in the assessment of the efficacy of treatments.

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.

The efficacy and safety of non-pharmacological therapies for the treatment of acne vulgaris: A systematic review and best-evidence synthesis.

BACKGROUND: Acne vulgaris is a multifaceted skin disorder, affecting more than 85% of young individuals worldwide. Pharmacological therapy is not always desirable because of the development of antibiotic resistance or the potential risk of adverse effects. Non-pharmacological therapies can be viable alternatives for conventional therapies. However, sufficient evidence-based support in the efficacy and safety of non-pharmacological therapies is lacking. OBJECTIVE: To assess the efficacy and safety of several non-pharmacological therapies in the treatment of acne vulgaris. METHODS: A systematic literature review, including a best-evidence synthesis, was performed to identify literature. Three electronic databases were accessed and searched for studies published between January 2000 and May 2017. RESULTS: Thirty-three eligible studies were included in our systematic review. Three main types of non-pharmacological therapies were identified laser- and light-based therapies, chemical peels and fractional microneedling radiofrequency. The majority of the included studies demonstrated a significant reduction in acne lesions. However, only seven studies had a high methodologic quality. Based on these seven trials, a best-evidence synthesis was conducted. Strong evidence was found for glycolic acid (10-40%). Moderate evidence was found for amino fruit acid (20-60%), intense pulsed light (400-700 and 870-1200 nm) and the diode laser (1450 nm). Initially, conflicting evidence was found for pulsed dye laser (585-595 nm). The most frequently reported side-effects for non-pharmacological therapies included erythema, tolerable pain, purpura, oedema and a few cases of hyperpigmentation, which were in most cases mild and transient. CONCLUSION: Circumstantial evidence was found for non-pharmacological therapies in the treatment of acne vulgaris. However, the lack of high methodological quality among included studies prevented us to draw clear conclusions, regarding a stepwise approach. Nevertheless, our systematic review including a best-evidence synthesis did create order and structure in resulting outcomes in which a first step towards future research is generated.

The journey of adult psoriasis patients towards biologics: past and present - Results from the BioCAPTURE registry.

BACKGROUND: A considerable disease period often precedes initiation of a biologic in patients with psoriasis. Little is known about this important period in patients' lives. Evaluation of this 'journey' can reveal important insights and opportunities for physicians and healthcare decision makers. OBJECTIVES: (i) To describe patient and treatment characteristics until the start of biologic treatment in patients with severe psoriasis, (ii) to assess shifts in early (2005-2009) versus established (2010-2015) biologics prescription periods, (iii) to assess changes in hospital/day care admissions before vs. after starting biologics. METHODS: Explorative, retrospective study on the treatment characteristics of the disease period until first biologic, presented with descriptive statistics of patients included in the BioCAPTURE registry. Journeys of 2005-2009 and 2010-2015 were compared with statistical tests to identify important shifts. RESULTS: Median TUS (time until conventional systemic) was 11.0 years and median TUB (time until biologic) was 18.9 years for all patients treated from 2005 to 2015. Most patients received three different conventional antipsoriatic systemic therapies. We noticed a small trend towards a shorter journey (TUB) with only two conventional systemic agents instead of three before initiating a biologic in later years (2010-2015, vs. 2005-2009). We also noticed a significant decrease in (day care) admissions comparing the two years before, versus the first two years after the start of a biologic treatment (17.7 vs. 8.6 admissions/100 follow-up years, P < 0.001). Cyclosporine, intensive topical treatment (dithranol), retinoids and PUVA therapy lost popularity in recent years. CONCLUSION: The 'journey' of patients with psoriasis towards a biologic is still long and characterized by many different treatments. Shifts towards fewer conventional drugs before biologic initiation and a clear decrease in hospital and day care admissions before vs. after a biologic are seen. Improvement of this journey, especially in young or recently diagnosed patients, can decrease negative influences on patients' lives and reduce societal impact.

Secukinumab treatment in new-onset psoriasis: aiming to understand the potential for disease modification - rationale and design of the randomized, multicenter STEPIn study.

BACKGROUND: To date, biological treatments have been assessed in subjects with a long-term history of psoriasis and previous failures to systemic and topical therapies. In rheumatoid arthritis and other immune-mediated inflammatory diseases, early intensive systemic treatment prolongs treatment-free remission. We hypothesize that, by treating patients with psoriasis early with an effective systemic therapy, we may be able to alter the clinical outcome and the natural course of the disease. The STEPIn study (NCT03020199) investigates early intervention with secukinumab versus narrow-band ultraviolet B (nb-UVB) phototherapy in subjects with new-onset psoriasis. OBJECTIVE: To determine whether early intervention with either nb-UVB treatment or secukinumab in subjects with new-onset plaque psoriasis might modify the natural course of the disease. METHODS: One hundred and sixty subjects aged 18-50 years with new-onset (≤12 months) moderate-to-severe plaque psoriasis and naïve to systemic treatment and phototherapy will be randomized to secukinumab 300 mg or nb-UVB. The Main Study has two treatment arms: Arm A1, subcutaneous secukinumab 300 mg at baseline, Weeks 1, 2, 3 and 4, and every 4 weeks thereafter until and including Week 52; Arm B1, one/two cycles of nb-UVB for 12 weeks each (maximum 28-week break between cycles). After treatment discontinuation, patients will be followed up and monitored for disease activity up to Week 208. A Mechanistic Sub-study will assess immunological changes and pathogenic tissue-resident memory T cells in skin biopsies. CONCLUSIONS: STEPIn is the first study to investigate whether early intensive treatment in new-onset psoriasis can modify the long-term natural course of the disease and thus become a novel treatment strategy for patients with psoriasis.

Determinants for drug survival of methotrexate in patients with psoriasis, split according to different reasons for discontinuation: results of the prospective MTX-CAPTURE.

BACKGROUND: As methotrexate (MTX) is a widely used treatment for psoriasis, it is important to gain insight into the reasons for the discontinuation of MTX and to understand the determinants for drug survival. OBJECTIVES: To describe 5-year drug survival for MTX in patients with psoriasis, split according to different reasons for discontinuation, and to identify the determinants for drug survival. METHODS: Data were extracted from a prospective psoriasis registry of patients treated with MTX (MTX-CAPTURE). Drug survival was analysed using Kaplan-Meier estimates and the determinants for discontinuation were analysed using Cox regression analysis. Analyses were split according to the reason for discontinuation: side-effects or ineffectiveness. RESULTS: We included 85 patients treated with MTX, with a maximum treatment duration of 5·2 years. The overall drug survival rates were 63%, 30% and 15% after 1, 3 and 5 years, respectively. The median survival was 1·8 years. Overall, 55 patients (65%) discontinued MTX for the following reasons: side-effects (35%), ineffectiveness (26%), combination of side-effects and ineffectiveness (13%), other reasons (16%) and 11% were lost to follow-up. The most reported side-effects were gastrointestinal symptoms, despite the use of folic acid in 99% of patients. Based on univariate analysis, a high Psoriasis Area and Severity Index score and a high score on the visual analogue scale for disease severity at baseline were possible determinants for a short drug survival. CONCLUSIONS: Drug survival of MTX was low with 15% of patients 'on drug' after 5 years. Side-effects alone or in combination with inadequate disease control were more important in the context of treatment discontinuation than inadequate disease control alone.

Validation of the Simplified Psoriasis Index in Dutch children and adolescents with plaque psoriasis.

BACKGROUND: The Simplified Psoriasis Index (SPI) is a three-domain assessment measure for psoriasis, including separate indicators of current severity (SPI-s), psychosocial impact (SPI-p), and past history and interventions (SPI-i). There are two complementary versions available designed for completion by a health professional (proSPI) or by patient self-assessment (saSPI). The validity and reliability of the proSPI vs. saSPI have already been demonstrated in adults. To date, validated severity measures for paediatric psoriasis do not exist. OBJECTIVES: To validate the current severity (SPI-s) and psychosocial impact (SPI-p) domains of the proSPI and saSPI in children and adolescents with psoriasis. METHODS: All patients aged < 18 years with plaque psoriasis visiting the dermatology outpatient department of Radboud University Medical Center, the Netherlands, between September 2013 and April 2014 were asked to complete Dutch versions of the saSPI and the Children's Dermatology Life Quality Index (CDLQI). The original English versions of the proSPI and Psoriasis Area and Severity Index (PASI) were completed by the physician at the same visit. RESULTS: In total, 113 patients (median age 12·0 years, range 4-17) were included. There was a close correlation between the proSPI-s and PASI (r = 0·87), which was higher than between the saSPI-s and PASI (r = 0·69). The correlation between the SPI-p and CDLQI was 0·78. The full range of scores was utilized in both proSPI-s and SPI-p, although the highest saSPI-s score was 30 (maximum 50). CONCLUSIONS: In paediatric psoriasis, the proSPI and saSPI are shown to be valid and usable. The SPI-s and SPI-p can be readily introduced into routine clinical practice.

Efficacy and safety of LAS41008 (dimethyl fumarate) in adults with moderate-to-severe chronic plaque psoriasis: a randomized, double-blind, Fumaderm® - and placebo-controlled trial (BRIDGE).

BACKGROUND: Fumaric acid esters (FAEs) are recommended in international guidelines for induction and long-term treatment of adults with moderate-to-severe chronic plaque psoriasis. The fixed combination Fumaderm® is approved in Germany, with dimethyl fumarate (DMF) being the main active ingredient. OBJECTIVES: To assess the efficacy and safety of a new formulation of DMF (LAS41008), compared with placebo and Fumaderm® , in adults with moderate-to-severe chronic plaque psoriasis. METHODS: In this phase III, double-blind, placebo-controlled, noninferiority trial (BRIDGE, NCT01726933, EudraCT 2012-000055-13), patients were randomized to receive LAS41008, Fumaderm® or placebo (2 : 2 : 1) for 16 weeks, uptitrating to a maximum daily DMF dose of 720 mg, depending upon individual response. The coprimary end points were the percentage of patients achieving ≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75) and the percentage achieving a score of 'clear' or 'almost clear' in the Physician's Global Assessment (PGA) at week 16. RESULTS: In total, 671 patients were randomized and included in the full analysis set (n = 267, LAS41008; n = 273, Fumaderm® ; n = 131, placebo). At week 16, 37·5% of patients treated with LAS41008 achieved PASI 75, compared with 15·3% receiving placebo (superiority for LAS41008 vs. placebo: P < 0·001) and 40·3% receiving Fumaderm® (noninferiority for LAS41008 vs. Fumaderm® : P < 0·001). Overall, 33% of patients treated with LAS41008 were 'clear' or 'almost clear' in the PGA at week 16, compared with 13·0% receiving placebo (P < 0·0001; LAS41008 superiority vs. placebo) and 37·4% receiving Fumaderm® . Most treatment-related adverse events were classed as 'mild' in severity. CONCLUSIONS: LAS41008 (DMF) is effective in the treatment of adults with moderate-to-severe chronic plaque psoriasis.

Predictors of perceived stigmatization in patients with psoriasis.

BACKGROUND: The physical appearance of psoriasis can be cosmetically disfiguring, resulting in a substantial social burden for patients. An important aspect of this burden is the experience of stigmatization. While stigmatization is known to be disabling and stressful for patients, little is known about its correlates, and effective interventions are lacking. OBJECTIVES: To examine predictor variables for perceived stigmatization in psoriasis. METHODS: Questionnaires were administered to 514 patients with psoriasis in a cross-sectional study. Zero-order correlation and multiple-regression analyses were conducted including sociodemographic, disease-related, personality, illness cognitions and social support predictor variables. RESULTS: Stigmatization was experienced by 73% of patients to some degree, and correlated with all five categories of predictor variables. In multiple-regression analyses, stigmatization was associated with higher impact on daily life; lower education; higher disease visibility, severity and duration; higher levels of social inhibition; having a type D personality; and not having a partner. CONCLUSIONS: The results indicate that perceived stigmatization is common in psoriasis, and can be predicted by sociodemographic, disease-related and personality variables. These predictor variables provide indications of which patients are especially vulnerable regarding perceived stigmatization, which might be used in treatment.

Polymorphisms in CD84, IL12B and TNFAIP3 are associated with response to biologics in patients with psoriasis.

BACKGROUND: The effectiveness of biologics for psoriasis shows heterogeneity among patients. With pharmacogenetic markers, it might be possible to predict treatment response. OBJECTIVES: We aimed to test the association between genetic markers and the response to biologics in psoriasis (etanercept, adalimumab, ustekinumab) in a prospective cohort. METHODS: We investigated the copy number variation in the LCE3B and LCE3C genes, and eight single-nucleotide polymorphisms (SNPs) in HLA-C*06, CD84, IL12B, IL23R, TRAF3IP2, ERAP1, IFIH1 and TNFAIP3. The decrease in Psoriasis Area and Severity Index (PASI) was calculated as ∆PASI (absolute PASI decrease compared with baseline) and PASI 75 (proportion of patients with ≥ 75% improvement vs. baseline). Associations between genetic variants and treatment outcome were assessed using multivariable linear regression analysis (∆PASI corrected for baseline PASI, primary analysis) and Pearson's χ2 -test or Fisher's exact test (PASI 75, secondary analysis). RESULTS: We included 348 treatment episodes in 234 patients. Patients heterozygous (GA) for the SNP in CD84 (rs6427528) had a better ∆PASI response to etanercept after 3 months (P = 0·025) than the homozygous reference group (GG). In addition, patients heterozygous (CT) for the IL12B variant showed a better response (∆PASI) to ustekinumab (P = 0·017) than the reference group (CC). Patients homozygous (GG) for the SNP in TNFAIP3 showed a worse response (∆PASI) to ustekinumab (P = 0·031) than the reference group (TT). The associations with ustekinumab resulting from the primary analysis were not confirmed in the secondary (PASI 75) analysis. CONCLUSIONS: We demonstrated a strong association between etanercept use in psoriasis and variations in CD84, a gene that was previously found to be a predictor of response to etanercept in rheumatoid arthritis.

Comparison of the 1- and 5-year effectiveness of adalimumab, etanercept and ustekinumab in patients with psoriasis in daily clinical practice: results from the prospective BioCAPTURE registry.

BACKGROUND: The efficacy of etanercept and ustekinumab in psoriasis has been compared in one randomized controlled trial. Comparison of the long-term effectiveness of biologics in daily-practice psoriasis treatment is currently lacking. OBJECTIVES: To compare the effectiveness between the three widely used outpatient biologics adalimumab, etanercept and ustekinumab in daily-practice psoriasis treatment and to correct for confounders. METHODS: Data were extracted from the prospective, multicentre BioCAPTURE registry. Multilevel linear regression analyses (MLRAs) and generalized estimating equation (GEE) analyses were performed on the course of mean Psoriasis Area and Severity Index (PASI) and PASI 75 (≥ 75% reduction vs. baseline). Both models were corrected for confounders. Subgroup analyses for biological dose were performed. RESULTS: We included 356 patients with 513 treatment episodes: 178 adalimumab, 245 etanercept and 90 ustekinumab. MLRA showed a similar effectiveness between adalimumab, etanercept and ustekinumab after 1 year, but the highest effectiveness for ustekinumab during 5 years of treatment (P = 0·047; ustekinumab vs. etanercept, P = 0·019). GEE analysis revealed a higher chance of attaining PASI 75 with adalimumab and ustekinumab than with etanercept at 1 year of treatment. A higher than label dose was more often used in patients treated with etanercept (adalimumab, etanercept and ustekinumab: respectively 31·5%, 55·1% and 17% after 1 year, P < 0·001; 39·3%, 71·4% and 24% after 5 years, P < 0·001). CONCLUSIONS: Compared with etanercept, ustekinumab had the highest effectiveness during 5 years of treatment. Patients receiving adalimumab and ustekinumab more often reached PASI 75 than those on etanercept at 1 year of treatment. Dose escalation was more frequent in etanercept and adalimumab than in ustekinumab.