Real-world outcomes and drug survival of brodalumab: results from the German Psoriasis Registry PsoBest.

Brodalumab, a human monoclonal antibody that targets interleukin-17 receptor A (IL-17RA), is approved in the US and EU for treatment of adults with moderate-to-severe plaque psoriasis. Although brodalumab has demonstrated efficacy and safety vs placebo in clinical trials of patients with psoriasis and psoriatic arthritis (PsA), real-world evidence is needed to evaluate long-term effectiveness and safety of brodalumab in routine care. This interim analysis of the German Psoriasis Registry PsoBest examined patient profiles, treatment outcomes, and drug survival of first-time use of brodalumab for 12 months in adult patients with moderate-to-severe plaque-type psoriasis (with and without PsA) (data cutoff: June 30, 2021). Clinician and patient-reported outcomes of the total cohort (n = 227; PsA, n = 38) indicated a rapid response to brodalumab treatment within the first 3 months, which was maintained up to 12 months. The overall one-year drug survival rate was 76.2%, the mean time to discontinuation was 8.3 months. Reasons for discontinuation were mainly loss/lack of effectiveness, followed by adverse events, contraindication and skin clearance. In sum, brodalumab demonstrated rapid and sustained effectiveness and was well-tolerated over 12 months in German patients with moderate-to-severe psoriasis and PsA in a real-world setting.

Sex differences in adverse events from systemic treatments for psoriasis: A decade of insights from the Swiss Psoriasis Registry (SDNTT).

BACKGROUND: Psoriasis is a disease that often requires prolonged systemic treatment. It is important to determine the safety of available therapies. There is currently little insight into sex-specific differences in the safety of systemic psoriasis therapies. OBJECTIVES: To examine the real-world, long-term safety of systemic psoriasis therapies with sex stratification in drug-related adverse events (ADRs). METHODS: Ten-year data from adults with moderate-to-severe psoriasis requiring systemic treatment (conventional systemic therapies [CST], biologics) were obtained from the Swiss psoriasis registry (SDNTT). ADRs were categorized according to the international terminology Medical Dictionary for Regulatory Activities (MedDRA). Safety was assessed by calculating event rates per 100 patient-years (PY). We used descriptive statistics for patient and disease characteristics, and binomial and t-tests to compare treatment groups and sex. RESULTS: In total, 791 patients (290 females) were included with a mean age of 46 years. 358 (45%) received CSTs and 433 (55%) biologics; both groups had similar baseline characteristics except for more joint involvement in patients using biologics (26.86% vs. 14.8%, p < 0.0001). CSTs were associated with a 2.2-fold higher ADR rate (40.43/100 PY vs. 18.22/100 PY, p < 0.0001) and an 8.0-fold higher drug-related discontinuation rate than biologics (0.16/PY vs. 0.02/PY, p < 0.0001). Trends showed non-significant higher serious adverse event rates per 100 PY for biologics (8.19, CI 6.87-9.68) compared to CSTs (7.08, CI 5.39-9.13) (p = 0.3922). Sex stratification revealed a significantly higher overall ADR rate for all treatments in females (1.8-fold for CSTs [57.30/100 PY vs. 31.69/100 PY] and 2.0-fold for biologics [27.36/100 PY vs. 13.9/100 PY], p < 0.0001), and drug-related discontinuation rates for most CSTs in females. CONCLUSION: Females were associated with a significantly higher rate of ADRs and drug-related discontinuation rates. Sex stratification should be taken into consideration when designing studies in the patient-tailored management of psoriasis.

Response to fumaric acid esters for plaque type psoriasis in real-world practice is largely independent of patient characteristics at baseline - a multivariable regression analysis from the German Psoriasis Registry PsoBest.

OBJECTIVES: Fumaric acid esters (FAEs) are a well-established treatment option for long-term therapy of moderate to severe plaque psoriasis. This study examines effectiveness of FAEs for the treatment of plaque psoriasis in real-world practice at 12 months and if patient characteristics affect the odds of clinical response. METHODS: A descriptive, multivariable logistic regression analysis was conducted in a cohort drawn from the German registry PsoBest. Baseline patient characteristics were assessed as potential treatment effect modifiers. RESULTS: 444 patients (mean age 47.0 years, 39.0% female) were eligible for response analysis using nonresponder imputation at month 12. Of these, 39.6% achieved clinical response, i.e. Psoriasis Area and Severity Index (PASI) ≤ 3 or skin clearance. In logistic regression analysis (R2 = 0.114), only baseline PASI was a significant factor: patients with PASI < 10 had a 4 times higher odds (p ≤ .001, OR 4.088), patients with PASI of 10-20 a twofold higher odds of response (p ≤ .044, OR 1.961) compared to those with PASI > 20. Neither sex, age, body weight, disease duration, comorbidity nor pretreatment had an impact on the odds of response (p > .05). CONCLUSIONS: FAEs showed a favorable response at 12 months, largely independent of patient characteristics.

Which PASI Outcome Is Most Relevant to the Patients in Real-World Care?

In psoriasis treatment, there is a high need to define meaningful endpoints and differences from the patient perspective to analyze patient-relevant differences of frequently used outcome methods for psoriasis under real-world conditions. A sample of 3116 patients from the German Psoriasis-Registry PsoBest was analyzed for clinical as well as patient-reported outcomes (PRO) after 3- and 6-month treatment. The parameters PASI, DLQI, and PBI were intercorrelated and related to two anchoring variables: (1) patient satisfaction with treatment and (2) perceived complete clearance. Baseline data were as follows: PASI 10.5 ± 9.1, DLQI 12.4 ± 3.4, and PBI 2.7 ± 0.3. There was an almost linear relationship between "complete patient satisfaction" and the relative differences in PASI in the range from PASI 25 to PASI 90. However, there was no additional benefit between PASI 90 and PASI 100. The same finding resulted from the anchoring variable "perception of complete healing". When related to DLQI outcomes, relative PASI changes as well as absolute changes and PASI at 3 and 6 months showed relevant differences between the PASI classes 25 to 90 but not between PASI 90 and PASI 100. Under real-world conditions, changes in PASI and DLQI reflect patient-relevant benefits.

[Predictors of Utilization of Cardiovascular and Respiratory Emergency Department Visits - what Impact does the Environment have?] / Prädiktoren der Inanspruchnahme von kardiovaskulären und respiratorischen Notfallaufnahmen ­ welchen Einfluss hat die Umwelt?

AIM: There has been an increasing number of emergency department (ED) visits recently. It is unclear whether, in addition to a shift in services from the outpatient to the inpatient sector, other causes, (e. g. environmental factors), play a role. The aim was to investigate associations between the number of cardiovascular and respiratory ED visits and environmental variables. METHODS: Highly correlated environmental data were subjected to a principal component analysis. By using cross-correlation functions, environmental variables with time lags that showed the highest correlation with the number of ED visits were taken into consideration in the UNIANOVA analysis model, together with, among others, the day of the week and interaction terms. RESULTS: The final regression model explained 47% of the variation in respiratory ED visits demonstrating main effects for Mondays (B=10.69; p<0.001). Season showed significant effects with highest ED visits in autumn. No direct associations between environmental variables and number of respiratory ED visits were found. The results for the cardiovascular outcome were less expressive (R2=0.20). Again, the day of the week had the main effect on cardiovascular ED visits (p<0.001). CONCLUSIONS: The results suggest that weekdays had the main effect on ED visits. In future, we will collect and analyze environmental data at the micro level to achieve a higher model quality and better interpretability.

Fumaric acid esters for the treatment of psoriasis in Germany: characterising patients in routine care.

BACKGROUND: Fumaric acid esters (FAE) represent the most widely-used oral systemic treatment for moderate-to-severe psoriasis in Germany. Not licensed outside Germany, little is known about the demographics of patients receiving FAE. PsoBest is a large national patient registry documenting long-term treatment of psoriasis in Germany. OBJECTIVES: To evaluate FAE relative to methotrexate (MTX) in patients from the PsoBest registry. MATERIALS AND METHODS: Patient demographics, disease severity at baseline and dosing regimen were reported for patients who initiated treatment with either FAE or MTX between 2007 and 2015. RESULTS: Overall, 1,409 patients treated with FAE and 877 with MTX were analysed. At baseline, compared with the MTX cohort, patients receiving FAE were younger (45.4 vs. 50.2 years; p≤0.001) and had a lower BMI (28.0 vs. 28.3 kg/m2; p≤0.023) and less nail involvement (45.4% vs. 50.7%; p≤0.013). The MTX cohort reported a greater mean duration of illness at baseline (18.2 years vs. 14.9 years; p≤0.001). In total, 85.6% and 58.5% patients in the FAE and MTX cohorts, respectively, had not received prior systemic therapy. Cardiovascular disease was the most prevalent comorbidity (FAE: 26.7%; MTX: 31.5%; p≤0.014). Health-related quality of life was similar for both cohorts (mean DLQI: 10.8 [FAE]; 10.5 [MTX]; p≤0.079). Mean FAE dose was 165.0 mg at inclusion and 406.4 mg following up-titration. CONCLUSION: This study contributes to a better understanding of the usual practices of long-term FAE use, which may also lead to improved treatment strategies not only in Germany, but in other countries where FAE may become available in the near future.

Poor Adherence to International Cancer Prevention Recommendations Among Patients With Prostate Cancer: First Results From the MARTINI-Lifestyle Cohort.

BACKGROUND: Promotion of a healthy lifestyle in patients with prostate cancer (PCa) has gained traction to increase patient investment in his/her health care practices, improve patient quality of life, and improve survival outcomes. OBJECTIVE: To investigate adherence of patients with PCa to healthy lifestyle recommendations from the World Cancer Research Fund (WCRF) and the American Institute for Cancer Research (AICR). DESIGN, SETTING, AND PARTICIPANTS: A total of 2227 men with PCa scheduled for radical prostatectomy in the Martini-Klinik at the University Hospital Hamburg-Eppendorf, Hamburg, Germany between January 2016 and December 2017. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Age and clinical characteristics were collected at the time of the diagnosis. Assessment of diet and physical activity data were obtained via e-mail surveys using validated questionnaires developed for the European Prospective Investigation into Cancer and Nutrition (EPIC) study [food frequency questionnaire, version 2 (FFQ2), EPIC-Physical Activity Questionnaire (EPIC-PAQ)]. Baseline characteristics were calculated as means and standard deviations for continuous data or counts and percentages for categorical data. RESULTS AND LIMITATIONS: Patients followed 3.3 (±1.5) of the 10 WCRF/AICR recommendations. None of the participants reached all goals; 67.3% of the patients did not fulfill the criteria of a healthy normal weight, 33.5% reported no exercise at all, and 49.6% were characterized as current or ex-smokers. As to nutritional goals, 75.4% did not meet the recommended intake of meat, 88.8% reported a low consumption of fruit and vegetables, and 86% did not achieve the recommended fiber intake. Because these analyses are based on self-reported data of diet and lifestyle, a bias toward underreporting cannot be excluded. CONCLUSIONS: First results of the MARTINI-Lifestyle cohort show that adherence to the AICR/WCRF recommendations for cancer prevention is poor. PATIENT SUMMARY: Patients with prostate cancer scheduled for surgery do not adhere to cancer prevention guidelines. Thus, improving lifestyle habits may provide significant impact on patient health and quality of life.

Smoking does not Alter the Therapy Response to Systemic Anti-psoriatic Therapies: A Two-country, Multi-centre, Prospective, Non-interventional Study.

Psoriasis can involve the skin, joints, nails and cardiovascular system and result in a significant impairment in quality of life. Studies have shown a lower response rate to systemic anti-psoriatic therapies in smokers, and smoking is a trigger factor for psoriasis. The aim of this study was therefore to analyse the response to systemic therapies for psoriasis, with a focus on smoking. Prospectively collected data from patients with moderate to severe psoriasis included in the national psoriasis registries for Germany and Switzerland (PsoBest and SDNTT) were analysed. Therapy response was defined as reaching a Psoriasis Area and Severity Index (PASI) reduction of 75%, PASI ≤ 3 or Dermatology Life Quality Index (DLQI) ≤ 1. Out of 5,346 patients included in these registries, 1,264 met the inclusion criteria for this study. In the smoking group, 715 (60.6%) reached therapy response at month 3, compared with 358 (63.7%) in the non-smoking group (p ≤ 0.269), 659 (74.1%) vs. 330 (77%) reached therapy response at month 6 (p ≤ 0.097), and 504 (76.6%) vs. 272 (79.0%) at month 12 (p ≤ 0.611). Therefore, these data do not show that smoking affects the response rate of anti-psoriatic therapy after 3, 6 and 12 months.

Biologics and immunoglobulins in the treatment of pyoderma gangrenosum - analysis of 52 patients.

BACKGROUND AND OBJECTIVES: Corticosteroids and cyclosporine A are frequently ineffective as first-line therapies in the treatment of pyoderma gangrenosum (PG) and associated with a number of adverse effects. The objective of the present study was to analyze the effectiveness and safety of biologics and intravenous immunoglobulins (IVIGs). PATIENTS AND METHODS: Retrospective, dual-center cohort study analyzing the treatment outcome in patients with PG who received biologics and IVIGs. RESULTS: Fifty-two patients (mean age: 58.4 years) with 75 wound episodes (mean wound size: 53.2 cm²) were included in the study. Overall, 92.3 % of patients initially received corticosteroids (CSs; 48/52); 51.9 % cyclosporine A (CSA; 27/52). In 275 therapeutic attempts, complete remission or improvement were achieved in 63.6 % (21/33) of patients on infliximab; 57.1 % (16/28) on adalimumab; 71.4 % (5/7) on etanercept; 66.6 % (6/9) on ustekinumab and 66.7 % (10/15) of patients who were given IVIGs. That figure was 48.8 % (38/78) for those treated with CSs and 20.0 % (7/35) for individuals on CSA. On average, adverse events occurred in 18.5 % (15/81) of cases treated with biologics in 20 % (3/15) of patients receiving IVIGs, in 40 % (14/35) of individuals on CSA and in 10.4 % of those treated with CSs (5/48). CONCLUSIONS: The present retrospective analysis suggests that both biologics - especially TNFα antagonists - and IVIGs are well-tolerated and safe options in the treatment of PG. Data from prospective comparative studies would be highly desirable.

Temporal analysis of determinants for respiratory emergency department visits in a large German hospital.

INTRODUCTION: Associations between air pollutants, meteorological conditions and respiratory diseases have been extensively shown. The aim of this study was to investigate associations between daily meteorological data, data on air pollution and emergency department (ED) visits depending on the day of the week, season and year (study period from 2013 to 2015). METHODS: Highly correlated environmental data entered a categorical principal components analysis (CATPCA). We analysed cross-correlation functions between the time series of the respective daily environmental factors and daily ED visits. Time lags with peak correlations of environmental variables obtained by the CATPCA on ED visits together with day of the week, year, running day (linear, quadratic and cubic), season and interaction terms entered the univariate analysis of variance (UNIANOVA) model. RESULTS: The analyses demonstrated main effects on ED visits for the day of the week with highest admission rates on Mondays (B=10.69; ƞ2=0.333; p<0.001). A significant time trend could be observed showing increasing numbers of ED visits per each year (p<0.001). The variable 'running day' (linear, quadratic and cubic) indicated a significant non-linear effect over time. The variable season showed significant results with winter, spring and summer recording fewer ED visits compared with the reference season autumn. Environmental variables showed no direct associations with respiratory ED visits. DISCUSSION: ED visits were significantly associated with temporal variables. Our data did not show direct associations between environmental variables and ED visits.In times of rapid urbanisation, increases in respiratory diseases, temperature and air pollution, our analyses can help focus future studies and enhance strategies to reduce increasing numbers of respiratory diseases and ED visits. Because the potential costs of medical care in hospitals can be high compared with physicians, public health recommendations for reducing the increasing ED visits should be promoted and evaluated.