Multinational Drug Survival Study of Omalizumab in Patients With Chronic Urticaria and Potential Predictors for Discontinuation.

Importance: Treating patients with chronic urticaria using omalizumab has been shown to be safe and effective in randomized clinical trials. Multinational studies on long-term omalizumab performance in chronic urticaria in clinical practice settings are lacking, especially on drug survival. Drug survival, which refers to the length of time that patients are treated with a specific drug, is a comprehensive outcome covering effectiveness, safety, and patient and physician preferences. Furthermore, little is known about the reasons and potential predictors for omalizumab discontinuation. Objective: To investigate omalizumab drug survival as well as reasons and potential predictors for discontinuation in a large, diverse population. Design, Setting, and Participants: This international multicenter cohort study was conducted at 14 Urticaria Centers of Reference and Excellence in 10 countries, including all patients with chronic urticaria from these centers who were ever treated with omalizumab. Main Outcomes and Measures: Drug survival analysis was performed to assess time to discontinuation. Patient characteristics and treatment protocols were investigated by Cox regression analysis to identify potential predictors for omalizumab discontinuation. Results: In 2325 patients with chronic urticaria who started omalizumab between June 2009 and July 2022, the mean (SD) age of the cohort was 42 (6) years, and 1650 participants (71%) were female. Overall omalizumab survival rates decreased from 76% to 39% after 1 to 7 years, respectively (median survival time, 3.3 [95 % CI, 2.9-4.0] years), primarily due to discontinuation from well-controlled disease in 576 patients (65%). Ineffectiveness and adverse effects were reasons for discontinuation in a far smaller proportion of patients, totaling 164 patients (18%) and 31 patients (4%), respectively. Fast treatment response was associated with higher rates of omalizumab discontinuation due to well-controlled disease (hazard ratio, 1.45 [95% CI, 1.20-1.75]), and disease duration of more than 2 years was associated with lower rates of discontinuation due to well-controlled disease (HR, 0.81 [95% CI, 0.67-0.98]). Immunosuppressive cotreatment at the start of omalizumab and autoimmune disease was associated with a higher risk for discontinuation due to ineffectiveness (HR, 1.65 [95% CI, 1.12-2.42]). The presence of spontaneous wheals (HR, 0.62 [95% CI, 0.41-0.93]) and access to higher dosages (HR, 0.40 [95% CI, 0.27-0.58) were both associated with a lower risk for discontinuation of omalizumab due to ineffectiveness. Conclusion and Relevance: This multinational omalizumab drug survival cohort study demonstrated that treatment of chronic urticaria with omalizumab in a clinical setting is effective and safe, and well-controlled disease is the main reason for treatment discontinuation. These findings on omalizumab drug survival rates and reasons and potential predictors for discontinuation may guide patients and physicians in clinical decision-making and expectation management. These results may call for the identification of biomarkers for chronic urticaria remission in complete responders to omalizumab treatment.

Effects of oral roflumilast therapy on body weight and cardiometabolic parameters in patients with psoriasis - results from a randomized controlled trial (PSORRO).

BACKGROUND: Weight loss is reported with oral roflumilast, which is approved for chronic obstructive pulmonary disease (COPD). Recently, the drug has shown efficacy in psoriasis, a disease strongly linked to overweight/obesity. OBJECTIVE: To describe the effects of oral roflumilast on body weight and cardio-metabolic parameters in patients with psoriasis. METHODS: Posthoc analyses from the PSORRO study, where patients with moderate-to-severe plaque psoriasis were randomized 1:1 to oral roflumilast 500 µg once-daily or placebo for 12 weeks, followed by active, open-label treatment through week 24 in both groups. Changes in body weight, blood pressure, gastrointestinal symptoms, and laboratory tests were registered. No lifestyle or dietary interventions were applied. RESULTS: Forty-six patients were randomized. Baseline characteristics across groups were comparable; mean weight was 103.6 kg. In patients receiving roflumilast, median weight change was -2.6% and -4% at week 12 and 24, respectively. Corresponding numbers were 0.0% and 1.3% in patients initially allocated to placebo. Reduced appetite was more frequent with active therapy. No changes in blood pressure or laboratory tests were observed. LIMITATIONS: Posthoc analyses and low numbers. CONCLUSION: Oral roflumilast induced weight loss and reduced appetite, which support the growing evidence of roflumilast as an attractive treatment alternative for patients with psoriasis.

CRUSE® -An innovative mobile application for patient monitoring and management in chronic spontaneous urticaria.

BACKGROUND: Chronic spontaneous urticaria (CSU) is unpredictable and can severely impair patients' quality of life. Patients with CSU need a convenient, user-friendly platform to complete patient-reported outcome measures (PROMs) on their mobile devices. CRUSE® , the Chronic Urticaria Self Evaluation app, aims to address this unmet need. METHODS: CRUSE® was developed by an international steering committee of urticaria specialists. Priorities for the app based on recent findings in CSU were defined to allow patients to track and record their symptoms and medication use over time and send photographs. The CRUSE® app collects patient data such as age, sex, disease onset, triggers, medication, and CSU characteristics that can be sent securely to physicians, providing real-time insights. Additionally, CRUSE® contains PROMs to assess disease activity and control, which are individualised to patient profiles and clinical manifestations. RESULTS: CRUSE® was launched in Germany in March 2022 and is now available for free in 17 countries. It is adapted to the local language and displays a country-specific list of available urticaria medications. English and Ukrainian versions are available worldwide. From July 2022 to June 2023, 25,710 observations were documented by 2540 users; 72.7% were females, with a mean age of 39.6 years. At baseline, 93.7% and 51.3% of users had wheals and angioedema, respectively. Second-generation antihistamines were used in 74.0% of days. CONCLUSIONS: The initial data from CRUSE® show the wide use and utility of effectively tracking patients' disease activity and control, paving the way for personalised CSU management.

Online Depiction of Urticaria Is Often Flawed and Does Not Reflect the Spectrum of Clinical Manifestation.

INTRODUCTION: The internet is a popular source of health information including images of disease manifestations. Online photographs of skin lesions may aid patients in identifying their disease, if these pictures are of good quality and of the disease they claim to show. If not, patients may be at risk of delayed diagnosis, misdiagnosis, and suboptimal treatment. For urticaria, the mismatch rate and quality of online pictures are unknown. The objective of this study was therefore to evaluate the content and quality of online images of urticaria. METHODS: The search term "urticaria" was applied to Google Images and Shutterstock. The top 100 photographs from each search engine were retrieved on October 9th, 2022. Illustrations, drawings, and heavily edited photographs were excluded. Each image was evaluated for patient characteristics, characteristics of urticarial lesions, and image quality. RESULTS: Across 194 unique images of urticaria (after removing duplicates), 35 (18.0%) did not depict urticarial lesions, and 38 (19.6%) were ambiguous. Less than two-thirds of images 121 (62.4%) showed bona fide urticarial lesions. Pictures of urticarial lesions under-represented children and did not reflect female preponderance of the disease. Images predominantly depicted urticaria lesions on Caucasian skin (59.8%) and were typical of spontaneous rather than inducible urticaria. Only 3 (1.5%) pictures showed angioedema, a common clinical sign in patients with urticaria. The overall quality of online urticaria pictures was mostly good or very good. CONCLUSION: Physicians and patients should be aware that one in five online pictures of urticaria does not show urticarial skin lesions, and children, females, non-Caucasian patients, inducible urticaria, and angioedema are under-represented. These findings should prompt efforts to improve the accuracy and representativeness of online urticaria pictures.

Occurrence and risk factors of mental disorders in patients with chronic urticaria.

This study aimed to evaluate the prevalence and risk factors of mental disorders in patients with chronic urticaria (CU) in a cohort of adult outpatients. Mental disorders occurred in almost one-sixth of the patients with CU, depression (9.7%), and anxiety (5.0%) being the most prevalent conditions. Furthermore, a significant difference in impairment of quality of life was seen between patients with mental disorders compared to patients without. Although, the prevalence of mental disorders in patients with CU is high, larger clinical studies are needed to investigate and understand the association and risk factors of mental disorders in patients with CU.

Smartphone photographs of chronic urticaria taken by patients are of good quality and useful in the clinic.

BACKGROUND: Chronic urticaria (CU) is characterized by transient wheals and angioedema, which are often not present when patients see their treating physician. AIM: To evaluate the diagnostic value of smartphone photographs captured by patients prior to their first visit at an urticaria outpatient clinic. METHODS: A survey regarding the quality and utility of smartphone photographs of urticarial skin lesions in patients with CU attending the outpatient clinic for the first time was conducted. Up to three random patient-selected photographs of skin lesions were evaluated by a physician. RESULTS: Of 148 patients, 118 (79.7%) had taken photographs of their skin lesions prior to the consultation, and 75% took photographs with the intention of presenting it to their physician. The photographs were of wheals in 90% of the cases, and angioedema in 8%. In total, 72% of the smartphone photographs had the skin lesion in focus, 64% had good resolution, 48% had good lighting. Only 9% of the smartphone photographs were blurred, 10% had bad lighting, 4% had bad resolution, and 8% did not have the lesion in focus. Moreover, 86% of the smartphone photographs were found to be useful for clinical evaluation. At least one photograph of good/very good quality was presented by 86% of the patients, and 97% had at least one photograph that was useful for clinical evaluation. CONCLUSION: Patients with CU often take smartphone photographs of their skin lesions on their own initiative prior to their first consultation to present the photographs to their physician. These smartphone photographs are very often of good quality and suitable for clinical evaluation.

Piloting a Mindfulness App for Use by Nursing Staff at Work.

This article discusses the findings of a 5-week pilot using a mindfulness app among medical-surgical nursing staff in an acute care setting during a 12-hour shift. Informational sessions on compassion fatigue, mindfulness, and the process were implemented with leadership providing daily support. The postimplementation survey demonstrated increased calmness and reduced stress. Barriers identified involve perceived time constraints. Awareness is needed on compassion fatigue, interventions to combat, and modifications to promote the culture of self-care.

Biomarkers for Monitoring Treatment Response of Omalizumab in Patients with Chronic Urticaria.

Chronic urticaria (CU) is a debilitating skin disease affecting around 1% of the population. CU can be subdivided into chronic spontaneous urticaria (CSU) and chronic inducible urticaria (CIndU). Different pathophysiological mechanisms have been proposed to play a role in the development of CU, and these are also being investigated as potential biomarkers in the diagnosis and management of the disease. As of now the only assessment tools available for treatment response are patient reported outcomes (PROs). Although these tools are both validated and widely used, they leave a desire for more objective measurements. A biomarker is a broad subcategory of observations that can be used as an accurate, reproducible, and objective indicator of clinically relevant outcomes. This could be normal biological or pathogenic processes, or a response to an intervention or exposure, e.g., treatment response. Herein we provide an overview of biomarkers for CU, with a focus on prognostic biomarkers for treatment response to omalizumab, thereby potentially aiding physicians in personalizing treatments.

Efficacy and safety of oral roflumilast for moderate-to-severe psoriasis-a randomized controlled trial (PSORRO).

Background: Roflumilast is a targeted inhibitor of phosphodiesterase (PDE)-4 and has been approved for treatment of severe chronic obstructive pulmonary disease for more than a decade. Generic versions are available in the United States. PDE-4 is involved in the psoriasis pathogenesis, but the efficacy and safety of oral roflumilast in patients with psoriasis have not previously been studied. Methods: A company-independent, multicenter, randomized, double-blind, placebo-controlled trial (ClinicalTrials.govNCT04549870). Patients were randomized 1:1 to receive monotherapy with oral roflumilast 500 µg once daily or placebo. At week 12, placebo patients were switched to open-label roflumilast through week 24. The primary endpoint was a 75% or greater reduction from baseline in the psoriasis area and severity index (PASI75) at week 12. Findings: In all, 46 patients were randomized (roflumilast, n = 23; placebo, n = 23). At week 12, significantly more patients in the active arm achieved PASI75 (8 of 23 patients [35%]) vs. placebo (0 of 23 patients [0%], with a difference vs. placebo of 8 [35%] patients, 95% CI: 3 [13%]-13 [57%] patients) (p = 0.014). At week 24, 15 (65%), 10 (44%), 5 (22%), and 2 (9%) of patients treated with roflumilast from week 0 had PASI50, PASI75, PASI90, and PASI100 responses (key secondary endpoints), respectively. The most prevalent, drug-related adverse events in both treatment groups were transient gastrointestinal symptoms, weight-loss, headache, and insomnia. A total of three patients (roflumilast n = 2; placebo, n = 1) discontinued therapy due to adverse events. Interpretation: Oral roflumilast was efficacious and safe in treating moderate-to-severe plaque psoriasis over 24 weeks. With generic versions available, this drug may represent an inexpensive and convenient alternative to established systemic psoriasis treatments. Funding: Financial support was received from Herlev and Gentofte Hospital, University of Copenhagen, and independent grants from private foundations in Denmark. No pharmaceutical company, including the market authorization holder of roflumilast, was involved in the study at any point.

The impact of home treatment and self-administration of omalizumab on chronic urticaria.

Background: Patients suffering from Chronic Spontaneous Urticaria (CSU) may be recalcitrant to treatment with high dose second-generation antihistamines. These patients are, according to international guidelines, eligible to treatment with omalizumab. Treatment with omalizumab has proven to be very effective for this group of patients. Until 2018, when the self-administration of omalizumab was approved, patients have had to visit an outpatient clinic to receive the treatment. Methods: In this study we performed a survey among 75 CSU patients who had changed their treatment from administration at an outpatient clinic to self-administration at home. Results: None of the patients experienced decreased effect of the treatment with omalizumab, whereas 41.4% reported improved effect of the treatment during self-administration.The most common reported benefits for the patients were decreased travel time and the ability to choose dosing time at the day of treatment, whereas the most reported concern was fear of performing the injection. Conclusions: Patients are very content with self-administration of omalizumab. There has been no decreased effect of the treatment, and as discussed in this paper, there might be other societal benefits from self-administration. Thus, self-administration at home of omalizumab should be standard of care when using this treatment.

Prevalence, predictors, and clinical relevance of α-gal sensitization in patients with chronic urticaria.

BACKGROUND: Little is known about α-gal (galactose-α-1,3-galactose) sensitization in patients with chronic urticaria (CU). The aim of this study was to examine the prevalence, predictors and clinical relevance of α-gal sensitization in patients with CU. METHODS: Two consecutive cohorts of newly referred patients with CU from a primary care allergology practice and a tertiary hospital dermatology department, plus a control group with allergic disease, but not CU, from the allergology practice, were interviewed and screened for α-gal sensitization (serum specific-IgE ≥0.35 KU/L). RESULTS: Of 733 patients included, 21 (5.6%) and 11 (3.9%) of CU patients from private practice and hospital, respectively, were α-gal sensitized. In total, 8 patients (38.1% of sensitized patients, and 2.1% of all CU patients) from private practice, and 2 patients (18.2% of sensitized patients, and 0.7% of all CU patients) from hospital, had clinically relevant α-gal allergy. In private practice, male sex (47.6 vs. 24.7%), p = 0.020, obesity (33.3 vs. 23.6%), p = 0.302, and frequency of angioedema (61.9 vs. 51.4%), p = 0.350; and in hospital, male sex (72.7 vs. 27.9%), p = 0.003, and high total immunoglobulin E (median 168 vs. 70.5 KU/L), p = 0.022 were associated with α-gal sensitization. CONCLUSION: α-gal sensitization is observed in a small fraction of CU patients with only few patients experiencing clinically relevant sensitization. Certain patients, particularly from primary care, may constitute a relevant population for aimed testing.

A job-exposure matrix addressing hand exposure to wet work.

PURPOSE: The aim of this study was to create a job-exposure matrix (JEM) for wet work. A JEM is a tool used to assess exposure to potential health hazards in occupational epidemiological studies. It can be used when counselling concerning job change/job choice, as a medico-legal tool when recognizing diseases as occupational and when planning interventions regarding prevention of, in this case, occupational hand eczema. METHODS: The study population was based on results from national surveys on working environment performed by the National Research Centre for the Working Environment in Denmark in 2000, 2005, and 2010 (National Research Centre for the Working Environment). We assessed responses on questions regarding wet hands, glove wear and total wet work. For the JEM a cutoff of 2 h total wet work/day was chosen as the exposure measurement. The proportion of responses of 2 h total wet work/day in each profession is illustrated as a number between 0 and 1 equal to 0-100% of the responses. RESULTS: Total wet work was most frequent among cleaners (domestic, office, and hotel cleaning), butchers and fishmongers, cooks, beauticians (hairdressers, barbers, related work) and health care workers (home-based personal workers, dentists, dental assistants). Regarding differences between sexes we found that indifferent of age and profession, women had 78% higher odds of having wet work. CONCLUSION: We found that wet work as an exposure varies among professions depending on whether wet hands or glove wear is assessed. A JEM is a useful tool to assess the extent of the exposure, wet work, independent of prior perceptions of classical wet work professions.

Simple, low-cost group-counselling programme vs treatment as usual for patients with newly notified occupational hand eczema-Exploratory analyses of effects on knowledge, behaviour and personal resources of the randomized PREVEX clinical trial.

BACKGROUND: Sickness absence in hand eczema patients has been associated with stress rather than disease severity, indicating that personal aspects regarding hand eczema should be investigated further. OBJECTIVES: To examine whether patient education vs treatment as usual can influence behaviour and knowledge regarding skin protection and care, as well as personal resources, in patients with occupational hand eczema. METHODS: PREVEX is an individually randomized clinical trial investigating the 1-year effects of a simple, low-cost group-counselling programme vs treatment as usual for patients with notified occupational hand eczema. Exploratory outcomes were behaviour, knowledge, self-efficacy, and self-evaluated skin care ability. RESULTS: In total, 1668 patients with notified occupational skin disease were invited to participate, of whom 769 were randomized and 756 were analysed: intervention group (n = 376) vs control group (n = 380). Behaviour was improved and the knowledge score increased in the intervention group as compared with the control group (respectively: estimate 0.08; 95%CI: 0.02-0.19; P = .01; and estimate 0.49; 95%CI: 0.28-0.70; P < .001). Self-efficacy was lower in the intervention group as compared with the control group (estimate -0.78; 95%CI: -1.25 to -0.30; P = .001). No difference was found regarding skin care abilities. CONCLUSIONS: The intervention had a positive influence on 1-year behaviour and knowledge, but was insufficient to result in long-term positive changes in personal resources regarding dealing with hand eczema.

Impact of hand eczema on quality of life: metropolitan versus non-metropolitan areas.

BACKGROUND: An inverse relationship between disease severity and health-related quality of life (HR-QoL) in patients with hand eczema is well established, but modifying effects of demographic variables have been less well studied. OBJECTIVE: To identify the influence of metropolitan versus non-metropolitan residence on the relationship between disease severity and HR-QoL in patients with occupational hand eczema. METHODS: The city of Copenhagen and the rest of Zealand were defined as metropolitan and non-metropolitan areas, respectively. Participants were 773 persons with occupational hand eczema. A questionnaire on the severity of hand eczema and HR-QoL was sent to all participants. RESULTS: The odds for reporting moderate to high severity of occupational hand eczema were significantly lower in the metropolitan population than in the non-metropolitan population [odds ratio (OR): 0.42; 95%CI: 0.23-0.75], whereas low dermatology-related quality of life was more prevalent in metropolitan than in non-metropolitan patients (OR: 1.31; 95%CI: 0.83-2.05), indicating that hand eczema had a more pronounced negative effect in metropolitan patients, in spite of less severe eczema. CONCLUSION: Our data indicate that area of residence has a modifying effect on the relationship between disease severity and HR-QoL, with a more negative impact on HR-QoL in metropolitan than in non-metropolitan areas. This information is important with respect to fully appreciating the burden of occupational hand eczema.