ActiPso: definition of activity types for psoriatic disease: A novel marker for an advanced disease classification.

BACKGROUND: Assessment of psoriasis is exclusively done measuring severity using somatic scores such as the psoriasis area and severity index or patient-reported outcomes such as the dermatology life quality index. There is no established tool to measure a patient's individual psoriasis activity over time. OBJECTIVES: Development of a new tool to classify psoriasis activity types. METHODS: Open patient interviews were performed and adapted in several steps and by using different groups of patients. Wording of the tool's axis and description how to use it was optimized with the input of patients. The final ActiPso tool was used in a prospective study in psoriasis patients. RESULTS: Four activity types could be identified describing psoriasis intensity (e.g. severity, itch, pain) over one typical year and an event/trigger type describing flares. In the study in 586 psoriasis patients of the 536 patients eligible for analysis 40.9% self-classified as type 1 ('stable'), 22.6% as type 2 ('unstable'), 30.6% as type 3 ('winter type') and 6.0% as type 4 ('summer type'), respectively. Flares of psoriasis as identified by the event/trigger type were reported in 36.1% of patients with activity type 1, 67.8% with type 2, 73.8% of type 3 and 59.4% of type 4, respectively. CONCLUSIONS: Interviewed patients were able to describe their course of psoriatic disease and to name potential triggering factors. By doing so, activity types of psoriasis were defined for the first time and the importance of events/triggers for flares described and integrated into ActiPso types as a basis for advanced patient-centric management. A limitation of ActiPso is that in regions with no seasonal variations types 3 and 4 may not apply.

Secukinumab 2-weekly vs. 4-weekly dosing in patients with plaque-type psoriasis: results from the randomized GAIN study.

BACKGROUND: Secukinumab is a fully human monoclonal antibody that selectively neutralizes interleukin-17A and shows long-lasting efficacy and safety in plaque psoriasis. More evidence is required to optimize secukinumab dosing according to clinical response. OBJECTIVES: GAIN compared the efficacy and safety of secukinumab 300 mg every 2 weeks (q2w) with 300 mg every 4 weeks (q4w) in patients achieving ≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75) but not PASI 90 after 16 weeks. METHODS: In total, 772 patients with moderate-to-severe plaque psoriasis received secukinumab 300 mg subcutaneously at baseline and weeks 1, 2, 3 and 4, then q4w until week 16. At week 16, patients with PASI ≥ 75 to PASI < 90 were randomized 1: 1 to continue q4w dosing (n = 162) or switch to q2w (n = 163) to week 32. The primary endpoint was superiority of q2w to q4w dosing for PASI 90 response at week 32. RESULTS: PASI 90 response at week 32 was numerically greater with secukinumab 300 mg q2w than with secukinumab 300 mg q4w in suboptimal responders, but this did not reach statistical significance (64·4% vs. 57·4%; odds ratio 0·64, 95% confidence interval 0·39-1·07; P = 0·087). Although the primary endpoint was not met, absolute PASI was significantly lower at week 32 in q2w vs. q4w patients (2·11 vs. 2·84, P = 0·024). Significantly more patients with q2w vs. q4w dosing showed minimal disease activity (Investigator's Global Assessment score 0 or 1: 73·0% vs. 64·1%, P < 0·05) and improved quality of life (Dermatology Life Quality Index score 0 or 1: 58·9% vs. 50·6%, P < 0·05) at week 32. No new or unexpected safety signals arose. CONCLUSIONS: Most patients achieved PASI 90 response with secukinumab q4w. There was potential benefit of q2w dosing in some suboptimal responders. Continued q4w treatment can improve response even after 16 weeks.

Psoriasis, cardiovascular risk factors and metabolic disorders: sex-specific findings of a population-based study.

BACKGROUND: Scientific evidence suggests an association between psoriasis and cardiovascular and metabolic diseases. However, there are hardly any sex-specific results from population-based studies reporting the prevalence of cardiovascular risk factors in patients with psoriasis and point estimates of the association between psoriasis and cardiovascular and metabolic disorders. OBJECTIVE: Aims are to evaluate the sex-specific prevalence of psoriasis and cardiovascular risk factors, and to estimate sex-specific associations between psoriasis and diabetes type 2 (DM) and metabolic syndrome (MetS). METHODS: We used data of 3723 participants (45-75 years, 54.1% women) without coronary heart disease and missing data (psoriasis, DM, MetS) from the Heinz Nixdorf Recall study. Standardized information on health outcomes and risk factors was assessed. We performed descriptive statistics and multiple regression analyses to calculate prevalence rate ratios (PR) and 95% confidence intervals (95% CI). RESULTS: The prevalence of psoriasis was 3.8% (n = 143), with no differences between sex. We observed more often metabolic and cardiovascular risk factors in women with psoriasis compared to women without psoriasis. Interestingly, in men, this pattern was partly reversed. Multiple regression analyses revealed distinctly elevated PRs for DM for both women and men with psoriasis (fully adjusted PR: 2.43; 95% CI: 1.17-5.07, resp. 2.09; 1.16-3.76). Regarding the MetS, the results were inconsistent, showing a positive association between psoriasis and MetS in women (1.84; 1.14-2.98), but a negative association in men, even though with a wide 95% CI (0.69; 0.42-1.12). CONCLUSION: The results of our cross-sectional, population-based analysis show a distinct association between psoriasis and DM, whereas for the MetS the results contrasted between men and women, translating in women with MetS showing a higher and in men a lower chance to be psoriatic. Our results emphasize the urgent need for sex-specific research, studying the effects of psoriasis on metabolic disorders as well as effective sex tailored prevention measures.

Secukinumab is effective in treatment of moderate-to-severe plaque psoriasis: real-life effectiveness and safety from the PROSPECT study.

BACKGROUND: Secukinumab, a fully human anti-interleukin-17A monoclonal antibody, has demonstrated efficacy and safety in patients with moderate-to-severe psoriasis. Trial protocols specify transition periods and prohibit concomitant psoriasis medication. Data are therefore needed on secukinumab effectiveness and safety in routine clinical practice. OBJECTIVES: The PROSPECT study assesses prior and concomitant psoriasis treatments and transition periods in subjects receiving secukinumab. Here, we report interim effectiveness and safety data for secukinumab in the context of prior and concomitant treatments. METHODS: PROSPECT is an ongoing 24-week, single-cohort, non-interventional study. Subjects with moderate-to-severe psoriasis with a decision to receive secukinumab 300 mg were included. RESULTS: Of 1988 subjects, 1238/1988 (62.4%) were male, and mean age was 48.1 ± 13.7 years. Mean baseline Psoriasis Area and Severity Index (PASI) score was 17.7 ± 12.5. 90.9% of subjects had prior systemic treatment. Concomitant treatment was recorded in 44.3% of subjects. Median duration of transition period was 14.0, 30.0 and 44.5 days from prior topical, conventional systemic and biologic treatments. At Week 24, PASI75/90/100 was reached by 86.1%, 68.5% and 39.7% of subjects who started secukinumab treatment at baseline. No unexpected safety signals were observed. CONCLUSION: PROSPECT provides a large prospective real-world analysis of secukinumab treatment and includes prior and concomitant use of psoriasis treatments in subjects receiving secukinumab in a real-world setting. Secukinumab effectiveness and safety were comparable to that seen in the phase 2/3 secukinumab clinical trial programme.

Prevalence, predictors and comorbidity of dry skin in the general population.

BACKGROUND: Dry skin is a frequent and multifaceted condition which can be associated with skin irritation, itch, patient discomfort and manifest skin disease. In spite of being frequent, little is known about the epidemiology of dry skin in the population. OBJECTIVE: To determine the prevalence of dry skin in the German adult population. METHODS: Data of 48 630 employed persons were assessed on a cross-sectional level in whole-body examinations by experienced dermatologists during company-based skin screenings conducted in 343 German companies. Next to the current dermatologic findings, age, gender, allergies, atopic diseases and the skin type were assessed. RESULTS: In total, n = 14 300 persons (29.4%) were rated as having xerotic skin. Older age but not gender was associated with xerosis. In the regression analyses controlling for age and gender, dry skin was a significant predictor for: axillary dermatitis (OR: 4.51; CI 2.70-7.54), atopic eczema (OR: 3.99; CI 3.42-4.65), exsiccation eczema (OR: 2.96; CI 2.40-3.65), psoriasis (OR: 1.57; CI 1.38-1.78), plantar warts (OR: 1.42; CI 1.26-1.60), seborrhoeic dermatitis (OR: 1.28; CI 1.16-1.42) and atopic disposition (OR: 1.17; CI 1.12-1.22). CONCLUSION: Dry skin is a frequent condition in the adult general population and needs special attention. Known risk factors may facilitate identifying patients at risk for deterioration.

Gender and age significantly determine patient needs and treatment goals in psoriasis - a lesson for practice.

BACKGROUND: Though patient needs are key drivers of treatment decisions, they are rarely systematically investigated in routine care. OBJECTIVE: This study aimed at analysing needs and expectations from the patient perspective in the German and Swiss psoriasis registries PsoBest and Swiss Dermatology Network of Targeted Therapies (SDNTT) with respect to treatment choice, age and gender. METHODS: The German and Swiss psoriasis registries observe patients recruited at first-time use of systemic drugs. Within 10 years, clinical [Psoriasis Area Severity Index (PASI), Body Surface Area (BSA)] and patient-reported outcomes are documented, including the Dermatology Quality of Life Index (DLQI) and the Patient Benefit Index (PBI), characterizing patient needs for treatment. The analysis data set includes n = 4894 patients from PsoBest and n = 449 from SDNTT with mean follow-up time of 7.5 months. RESULTS: A total of 5343 patients registered between 2008 and 2016 were included in the analyses (at baseline: 59.6% male, mean age 47.6 years ± 14.5, PASI 14.2 ± 9.7, BSA 22.7 ± 19.7, DLQI 11.3 ± 7.2). The most important patient needs were to 'get better skin quickly' and to 'be healed of all skin defects'. Subgroup analyses by age revealed significant differences in needs, especially higher needs regarding social impairments in patients younger than 65 years. Patients 65 years or older attributed more importance to sleep quality, less dependency on medical visits, fewer side-effects and confidence in the therapy. Out of 25 items reflecting patient needs, 20 items were rated significantly more important by women than men, with the greatest differences regarding feeling of depression, sleep quality and everyday productivity. Divided by treatment, needs were rated differently, recommending individualized and targeted choice of therapy. CONCLUSION: Age and gender stratify patient needs. Women showed higher expectations and rated specific needs in psoriasis treatment higher than men. Analysing the patient needs on an individual level will facilitate shared decisions by patient and physician in finding the optimal personalized treatment.

Definition of psoriasis severity in routine clinical care: current guidelines fail to capture the complexity of long-term psoriasis management.

BACKGROUND: Assessment of disease severity is an essential component of psoriasis management. Moderate-to-severe disease qualifies for systemic treatment but different definitions are used. OBJECTIVES: To analyse the impact of different severity definitions for psoriasis in real-world healthcare. METHODS: Cross-sectional data on 3274 patients with psoriasis from more than 200 dermatology offices and clinics across Germany were analysed for disease severity based on Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI). The proportions of patients having moderate-to-severe disease were determined accordingly. RESULTS: The proportion of patients meeting the European consensus criteria for moderate-to-severe psoriasis (PASI AND DLQI > 10) was 14·0%, although 45·3% attained at least PASI OR DLQI > 10. Consideration of all patients on systemic drugs as being 'moderate-to-severe' increased these proportions to 56·9% and 75·2%, respectively. When only PASI > 10 was used, moderate-to-severe disease affected 35·3% and 69·3%, respectively. CONCLUSIONS: The proportion of patients with psoriasis under dermatological care considered to have moderate-to-severe disease varies considerably according to how the latter is defined, resulting in uncertainty and inequity of access to systemic therapy. We propose an international standardisation in this for the sake of more reliable treatment and healthcare planning.

[Insufficient tetanus vaccination protection in psoriasis and systemic immunosuppression : Results of a retrospective investigation of 101 patients]. / Unzureichender Tetanusimpfschutz bei Psoriasis und systemischer Immunsuppression : Ergebnisse einer retrospektiven Untersuchung an 101 Patienten.

BACKGROUND: With a prevalence of approximately 3 % worldwide, psoriasis is one of the most frequent chronic inflammatory skin diseases. Patients with moderate to severe psoriasis are treated guideline-conform with immunomodulatory or immunosuppressive agents. According to current guidelines physicians should be vigilant about the vaccination status of immunosuppressed patients. OBJECTIVE: The aim of the study was to serologically objectify the tetanus vaccination status in systemically treated patients with moderate to severe psoriasis in Germany. MATERIAL AND METHODS: Within the context of this retrospective study the concentration of immunoglobulin G antibodies against Clostridium tetani was determined in 101 patients with systemic immunosuppression suffering from psoriasis. RESULTS: In a total of 27.7% (n = 28; 11 male, 17 female) of the patients, insufficient immunoglobulin G antibody concentrations were detected, corresponding to a higher risk of an infection with C. tetani. Group subanalyses indicated an insufficient tetanus protection especially in patients ≥65 years old (50%). CONCLUSION: The tetanus immune status of psoriasis patients was shown to be comparable with the general population. The results of our investigation underline that people suffering from psoriasis have to be tested for tetanus protection and if necessary, vaccinations have to be renewed.

The genetic basis for most patients with pustular skin disease remains elusive.

BACKGROUND: Rare variants in the genes IL36RN, CARD14 and AP1S3 have been identified to cause or contribute to pustular skin diseases, primarily generalized pustular psoriasis (GPP). OBJECTIVES: To better understand the disease relevance of these genes, we screened our cohorts of patients with pustular skin diseases [primarily GPP and palmoplantar pustular psoriasis (PPP)] for coding changes in these three genes. Carriers of single heterozygous IL36RN mutations were screened for a second mutation in IL36RN. METHODS: Coding exons of IL36RN, CARD14 and AP1S3 were sequenced in 67 patients - 61 with GPP, two with acute generalized exanthematous pustulosis and four with acrodermatitis continua of Hallopeau. We screened IL36RN and AP1S3 for intragenic copy-number variants and 258 patients with PPP for coding changes in AP1S3. Eleven heterozygous IL36RN mutations carriers were analysed for a second noncoding IL36RN mutation. Genotype-phenotype correlations in carriers/noncarriers of IL36RN mutations were assessed within the GPP cohort. RESULTS: The majority of patients (GPP, 64%) did not carry rare variants in any of the three genes. Biallelic and monoallelic IL36RN mutations were identified in 15 and five patients with GPP, respectively. Noncoding rare IL36RN variants were not identified in heterozygous carriers. The only significant genotype-phenotype correlation observed for IL36RN mutation carriers was early age at disease onset. Additional rare CARD14 or AP1S3 variants were identified in 15% of IL36RN mutation carriers. CONCLUSIONS: The identification of IL36RN mutation carriers harbouring additional rare variants in CARD14 or AP1S3 indicates a more complex mode of inheritance of pustular psoriasis. Our results suggest that, in heterozygous IL36RN mutation carriers, there are additional disease-causing genetic factors outside IL36RN.

[Secukinumab-induced subacute-cutaneous lupus erythematosus]. / Secukinumab-induzierter subakut-kutaner Lupus erythematodes.

We report about a 52-year-old woman with onset of drug-induced lupus erythematosus (DILE) in sun-exposed areas, under therapy with secukinumab. Topical therapy with a steroid class 3 for 4 weeks showed substantial improvement. The systemic therapy was switched to ustekinumab. DILE is a rare but notable side effect of biologicals in 0.5-1% of the patients and also possible under therapy with IL-17 inhibition. Switch of the biological agent is necessary in most cases.

Secukinumab treatment of moderate to severe plaque psoriasis in routine clinical care: real-life data of prior and concomitant use of psoriasis treatments from the PROSPECT study.

BACKGROUND: Secukinumab, a fully human anti-interleukin-17A monoclonal antibody, has demonstrated efficacy and safety in patients with moderate to severe psoriasis. However, as per study protocols, transition periods from prior psoriasis treatments of a defined minimal length were required and use of concomitant psoriasis medication was prohibited. There is therefore a lack of data on the effect of shorter transition periods and concomitant psoriasis treatment with other pharmacologically active substances on the effectiveness and safety of secukinumab in routine clinical practice. OBJECTIVES: The PROSPECT study was designed to assess prior and concomitant use of psoriasis treatments in subjects receiving secukinumab and the duration of transition periods from prior treatments to secukinumab. Here, we report the baseline characteristics and the duration of transition period in an interim analysis of the first 805 subjects. METHODS: PROSPECT is an ongoing 24-week, single-cohort, non-interventional study. Subjects with moderate to severe psoriasis with a decision to receive secukinumab were included. RESULTS: The majority of subjects were male (491/796, 61.7%), with a mean age of 47.7 years (SD 13.7). The baseline Psoriasis Area and Severity Index (PASI) was available for 92.4% (744/805) of subjects, and mean baseline PASI was 17.5 (SD 13.1); 93.4% (752/805) of subjects had signs of high disease severity. Use of concomitant treatment increased with the number of signs. Within the last 12 months prior to inclusion, 10%, 40%, and 28% of subjects had received topical, conventional systemic, or biologic treatments as their last prior psoriasis therapy, respectively, and 22% of subjects had not received any psoriasis therapy. Discontinuation of prior treatment due to adverse events was high in subjects with conventional systemic treatment (93/413, 22.5%) compared to biologic treatment (5/210, 2.4%). The median duration of the transition period was 14.0, 30.5, and 38.0 days for prior topical, conventional systemic, and biologic treatments, respectively. CONCLUSION: PROSPECT is the first study to investigate prior and concomitant use of psoriasis treatments in subjects receiving secukinumab in a real-world setting. The majority of the subjects had a high disease burden and use of concomitant treatment increased with disease severity. The duration of the transition period depended on prior treatment.

[First manifestation of leg ulcers : Analysis of data from 1000 patients]. / Erstmanifestation eines Ulcus cruris : Analyse der Daten von 1000 Patienten.

BACKGROUND: More than 1 million people in Germany suffer from leg ulcers. The diagnosis leg ulcer summarizes many different etiologies. The therapy of leg ulcers is an interdisciplinary and interprofessional challenge. Early identification of the cause of the leg ulcer and initiation of a causal therapy are essential for healing. OBJECTIVES: The aim of this study was to investigate the initial manifestation age of patients with causally associated leg ulcers. Afterwards we calculated the most common etiologies according to decade. PATIENTS AND METHODS: A prospective database at the University Hospital Essen, dermatological wound care center, was used to identify patients with chronic leg ulcers between 2002 and 2014. Clinical data of 1000 patients with chronic leg ulcers were analyzed in this monocentric study. RESULTS: A total of 29 different etiologies were differentiated. Approximately 70% of etiologies were of vascular origin, while 30% were rare causes. The count of different etiologies showed significant differences related to the onset and the occurrence in individual decades of life. In particular, nonvascular etiologies such as pyoderma gangrenosum or necrobiosis lipoidica are relatively more common in younger patients than in the aged. CONCLUSION: Based on the findings of our study, it is possible to limit the underlying etiology on the basis of the age of first manifestation of the leg ulcer in order to make targeted diagnostics more effective. Thus, this information can help to optimize scarce time resources in daily practice and improve the prediction probability of leg ulcers.

The impact of age on psoriasis health care in Germany.

INTRODUCTION: Inequality between age groups has been demonstrated in the prescription of biologics, yet systematic real-world data about age-related differences in psoriasis care are missing. OBJECTIVE: To investigate disparities in psoriasis characteristics by age groups and to identify potential impact on psoriasis health care. PATIENTS AND METHODS: Data analysis included 3615 patients from the German psoriasis registry PsoBest, which observes adult patients with moderate-to-severe psoriasis or psoriatic arthritis (PsA) on systemic treatment over a time period of 10 years. RESULTS: With 2376 participants (65.7%), the majority of patients was assigned to the age group 35-64, followed by 776 (21.4%) and 463 (12.8%) for the age groups 18-34 and 65+, respectively. Psoriasis vulgaris was the most frequent form of psoriasis with nearly 90% patients affected. Appearance of psoriasis forms did not differentiate significantly between the age groups except for erythrodermic psoriasis, which was more frequent in the elderly than in patients aged 35-64 (1.9%, P ≤ 0.048). Nail psoriasis appeared significantly more often in patients aged 35-64 (55.5%, P ≤ 0.001) and also showed the highest number of nails involved (6.9 ± 3.3). PsA was less frequent in the age group 18-34 (9.5%, P ≤ 0.001). This group showed the highest rate of scalp psoriasis (85.8%) compared to the elder age groups (P ≤ 0.001). Biologicals were used significantly less in younger patients (16.2%) compared to the age groups 35-64 (23.9%, P ≤ 0.001) and 65+ (21.8%, P ≤ 0.042). CONCLUSION: Middle-aged patients show higher rates of PsA and nail psoriasis, which may explain age-dependent disparities in health care including the use of systemic treatment.

High mobility group box 1 is increased in the sera of psoriatic patients with disease progression.

BACKGROUND: Psoriasis vulgaris (PV) is an autoimmune-related chronic inflammatory disease, which appears mostly in skin, but also affects the vascular and metabolic system. The incidence of PV is 2-3% in the general population and there is still no possibility to cure. Trigger factors have been identified to initiate and maintain inflammation in the skin, which is characterized by Th1-, Th17- and Th22- cells. OBJECTIVE: We hypothesize that the damage-associated molecular pattern (DAMP) molecule high mobility group box 1 (HMGB1) plays a role in the pathogenesis of PV. HMGB1 is a DNA-binding protein located in the nucleus, which acquires cytokine-like properties once released from the cell upon necrotic cell death or actively secreted by immune cells in inflammation and cancer. METHODS: We recruited 90 psoriatic patients under and without therapy with mild, intermediate and severe progression of disease, defined by the Psoriasis Area Severity Index. Serum levels of HMGB1 in patients with PV were detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: Our results show an increased level of HMGB1 in the sera of patients with PV in comparison to healthy donors. Furthermore, our analyses reveal that HMGB1 levels are significantly increased with disease progression and are downregulated after standard therapies for PV have been conducted. CONCLUSION: Our data provide insights into a possible role of HMGB1 for inflammation in PV.

[Successful treatment of a patient with ulcerated necrobiosis lipoidica non diabeticorum with adalimumab]. / Erfolgreiche Behandlung einer Patientin mit therapierefraktärer, exulzerierter Necrobiosis lipoidica non diabeticorum mit Adalimumab.

Necrobiosis lipoidica is a rare inflammatory granulomatous skin disease of unknown etiology which is associated with diabetes mellitus in about 60 % of the patients. In up to 30 % of these patients extremely painful and often hard-to-heal ulcerations occur in the course of the disease. We present a new therapeutic option using adalimumab to treat refractory ulcerated necrobiosis lipoidica non diabeticorum. The clinical efficacy of adalimumab probably reflects an immunomodulatory effect through the specific TNF-α inhibition which is one central aspect of the underlying inflammation. Thus, adalimumab could represent promising new treatment option, especially for patients with otherwise therapy-refractory ulcerated necrobiosis lipoidica.