Clinical Outcomes, Patient-Reported Outcomes, and Economic Burden for Thai People Living with Chronic Urticaria (CORE-CU) in routine practice: A study protocol for a monocentric prospective longitudinal study.

BACKGROUND: Few prospective longitudinal studies have been conducted in Thailand to account for the long-term response to chronic urticaria (CU) treatment, clinical outcomes, and patient-reported outcomes (PROs) among people living with CU based on routine practice. As such, a prospective longitudinal study will be conducted to better understand the long-term responses to treatment options and the burden of disease in Thai CU patients. METHODS AND DESIGN: This study is a routine clinical practice registry-based, monocentric, prospective, observational longitudinal study in the northern region of Thailand. Adult patients in an outpatient clinic diagnosed with CU, including both chronic spontaneous urticaria and chronic inducible urticaria will be recruited for this study. The cohort will be collected and registered using the joint routine clinical practice data based on multiple datasets including claims outpatient and inpatient data, routine laboratory results, medication utilization, health care costs, clinical characteristics, long-term urticaria care and monitoring, and PRO measures. The point prevalence of adverse health outcomes will be estimated and reported corresponding to 95% confidence intervals (95% CIs). The overall trend analysis will be analyzed to explore the effect of over time across the cohort time frame. CONCLUSION: This prospective longitudinal study will report the clinical outcomes, PROs, and economic burden among Thai people living with CU based on routine clinical practice. Findings will provide comprehensive evidence and could facilitate best practices for CU care management for health care professionals, researchers, policymakers, and public society. TRIAL REGISTRATION: Thai Clinical Trials Registry (TCTR, thaiclinicaltrials.org) registration TCTR20210706005. Registered on July 6, 2021.

Tree-based data mining for safety assessment of first COVID-19 booster doses in the Vaccine Safety Datalink.

BACKGROUND: The Centers for Disease Control and Prevention's Vaccine Safety Datalink (VSD) has been performing safety surveillance for COVID-19 vaccines since their earliest authorization in the United States. Complementing its real-time surveillance for pre-specified health outcomes using pre-specified risk intervals, the VSD conducts tree-based data-mining to look for clustering of a broad range of health outcomes after COVID-19 vaccination. This study's objective was to use this untargeted, hypothesis-generating approach to assess the safety of first booster doses of Pfizer-BioNTech (BNT162b2), Moderna (mRNA-1273), and Janssen (Ad26.COV2.S) COVID-19 vaccines. METHODS: VSD enrollees receiving a first booster of COVID-19 vaccine through April 2, 2022 were followed for 56 days. Incident diagnoses in inpatient or emergency department settings were analyzed for clustering within both the hierarchical ICD-10-CM code structure and the follow-up period. The self-controlled tree-temporal scan statistic was used, conditioning on the total number of cases for each diagnosis. P-values were estimated by Monte Carlo simulation; p = 0.01 was pre-specified as the cut-off for statistical significance of clusters. RESULTS: More than 2.4 and 1.8 million subjects received Pfizer-BioNTech and Moderna boosters after an mRNA primary series, respectively. Clusters of urticaria/allergy/rash were found during Days 10-15 after the Moderna booster (p = 0.0001). Other outcomes that clustered after mRNA boosters, mostly with p = 0.0001, included unspecified adverse effects, common vaccine-associated reactions like fever and myalgia, and COVID-19. COVID-19 clusters were in Days 1-10 after booster receipt, before boosters would have become effective. There were no noteworthy clusters after boosters following primary Janssen vaccination. CONCLUSIONS: In this untargeted data-mining study of COVID-19 booster vaccination, a cluster of delayed-onset urticaria/allergy/rash was detected after the Moderna booster, as has been reported after Moderna vaccination previously. Other clusters after mRNA boosters were of unspecified or common adverse effects and COVID-19, the latter evidently reflecting immunity to COVID-19 after 10 days.

Assessment of selected interleukins (IL-6, IL-17A, IL-18, IL-23) and chemokines (RANTES, IP-10) in children with acute and chronic urticaria.

BACKGROUND: Urticarial lesions develop as a result of the activation of mast cells which, through the release of mediators, influence the formation of local inflammatory infiltrates. Changes in the expression of many cytokines and chemokines are observed in the course of urticaria. The aim of the study was to evaluate serum levels of interleukin (IL)-6, IL-17A, IL-18, IL-23, regulated on activation, normal T cell expressed and secreted (RANTES) and interferon (IFN)-γ-inducible protein-10 (IP-10) in children with acute urticaria and exacerbation of chronic urticaria in comparison to healthy volunteers. Moreover, we made an attempt to identify factors associated with the acute phase of urticaria and factors predicting the course of the disease among the studied parameters. METHODS: We retrospectively analyzed 32 children with acute urticaria and 32 children with chronic urticaria. The control group consisted of 40 healthy children. Each patient was clinically evaluated. Serum concentrations of selected cytokines and chemokines were determined by using enzyme-linked immunosorbent assay. RESULTS: Patients with acute and chronic urticaria had higher concentrations of IL-6 and IL-17A (p < 0.001) and lower concentrations of IL-18, IL-23, RANTES and IP-10 (p < 0.001) as compared to the control group. A significant association between IL-6 and IP-10 with the acute phase of urticaria has been demonstrated. There was no correlation of the studied cytokines and chemokines with disease activity. CONCLUSIONS: In children with acute phase of urticaria, the cytokine serum concentration differs compared to healthy subjects. IL-6 and IP-10 seem to be useful in differentiating children with acute phase of urticaria and healthy ones. The search for factors predicting the course of the disease requires further studies.

Cost-effectiveness of personalized omalizumab dosing for chronic spontaneous urticaria.

The licensed dose for omalizumab within Europe for chronic spontaneous urticaria (CSU) is 300 mg every 4 weeks, and is based on the most effective dose identified in clinical trials. However, many patients require longer-term treatment with omalizumab and there is limited guidance on how to manage these patients. We report on a large cohort of 357 patients with CSU who have been treated over a 10-year period on a personalized dosing regimen. Our results showed a 4% reduction in drug cost for this personalized dosing regimen compared with having all patients on the standard regimen of omalizumab 300 mg every 4 weeks. In addition, by increasing the dose, we were able to treat 22% of patients more effectively, using the principle aim of zero CSU symptoms; prior to this regimen, these patients had been achieving only partial response. Omalizumab doses and frequency should be adjusted depending on clinical response to allow for improved benefits for both patients and healthcare systems.

Trends in the Cost and Utilization of Omalizumab in the Medicare Population: 2013-2017.

Background: Omalizumab has been demonstrated to be effective in treating chronic spontaneous urticaria (CSU) and was FDA approved for this indication in 2014. Previous work has shown that access to injectable biologics varies across US counties. In the present study we evaluate geographic and temporal trends in the utilization of omalizumab in the Medicare population by dermatologists, with its use by allergists and pulmonologists as comparators. Methods: We analyzed year-over-year trends in omalizumab utilization across geographic regions using the Medicare Provider Utilization and Payment Data: Part D files. Results: Utilization of omalizumab by dermatologists increased rapidly after its FDA approval, from 0.08 claims/100,000 enrollees totaling $209/100,000 enrollees in 2014 to 1.45 claims/100,000 enrollees totaling $3115/100,000 enrollees in 2017. Nonetheless, prescribing dermatologists were present in only 2.8% (95% Confidence Interval (CI): 2.0%-3.9%) and 0.2% (95% CI: 0.0%-0.5%) of metropolitan and non-metropolitan counties, respectively, in 2017, demonstrating limited availability, especially in non-metropolitan counties. Similarly, prescribers of any specialty were available in 32.9% (95% CI: 30.2%-35.6%) and 3.8% (95% CI: 3.1%-4.8%) of metropolitan and non-metropolitan counties, respectively, in 2017. Conclusions: Our data suggest that despite increasing omalizumab utilization, there remains a lack of access across many counties, particularly in non-metropolitan regions. Efforts to expand omalizumab prescriber accessibility in these counties may improve outcomes for patients with CSU.

A Specialized Therapeutic Approach to Chronic Urticaria Refractory to H1-Antihistamines Improves Disease Burden: The Spanish AWARE Experience.

OBJECTIVE: During its first year, the AWARE study assessed disease activity, patient quality of life (QOL), and treatment patterns in chronic urticaria (CU) refractory to H1-antihistamines (H1-AH) in clinical practice. METHODS: We performed an observational, prospective (24 months), international, multicenter study. The inclusion criteria were age ≥18 years and H1-AH-refractory CU (>2 months). At each visit, patients completed questionnaires to assess disease burden (Urticaria Control Test [UCT]), disease activity (7 day-Urticaria Activity Score [UAS7]), and QOL (Dermatology Life Quality index [DLQI], Chronic Urticaria Quality of Life Questionnaire [CU-Q2oL], and Angioedema Quality of Life Questionnaire [AE-QoL]). We present data for Spain. RESULTS: The study population comprised 270 evaluable patients (73.3% female, mean [SD] age, 48.9 [14.7] years). At baseline, 89.3% were prescribed a CU treatment. After 1 year, first- and second-line treatments became less frequent and third-line treatments became more frequent. At baseline, 47.0% of patients experienced angioedema; at 1 year, this percentage had fallen to 11.8%. The mean (SD) AE-QoL score decreased from 45.2 (28.7) to 24.0 (25.8). The mean (SD) UCT score decreased from 7.0 (4.5) to 12.1 (4.1). According to UAS7, 38.2% of patients reported absence of wheals and itch in the previous 7 days at 1 year compared with 8.3% at baseline. The mean (SD) DLQI score decreased from 8.0 (7.4) to 2.8 (4.6). At the 1-year visit, the percentage of patients reporting a high or very high impact on QOL fell from 29.9% to 9.6%. CONCLUSION: H1-AH-refractory CU in Spain is characterized by absence of control of symptoms and a considerable impact on QOL. Continuous follow-up of CU patients and third-line therapies reduce disease burden and improve patients' QOL.

Prevalence, Management, and Anaphylaxis Risk of Cold Urticaria: A Systematic Review and Meta-Analysis.

BACKGROUND: Cold urticaria is a subtype of chronic inducible urticaria (CIndU) associated with significant morbidity and a risk for anaphylaxis. Few studies have assessed the prevalence, management, and prevalence of associated anaphylaxis of cold urticaria. OBJECTIVES: To evaluate the prevalence of cold urticaria among CIndU and chronic urticaria (CU) cases, to assess the management of cold urticaria, and to determine the prevalence of associated anaphylaxis. METHODS: We searched PubMed and EMBASE for studies pertaining to cold urticaria and/or CIndU published in the past 10 years. We conducted meta-analyses to evaluate the prevalence of cold urticaria among CIndU and CU cases, the management of cold urticaria with H1-antihistamines and omalizumab, and the prevalence of associated anaphylaxis. RESULTS: Twenty-two studies were included in the systematic review and 14 in the meta-analysis. The pooled prevalence of cold urticaria among patients with CU and CIndU was 7.62% (95% confidence interval [CI], 3.45% to 15.99%; I2 = 98%) and 26.10% (95% CI, 14.17% to 43.05%; I2 = 97%), respectively. Cold urticaria was managed by H1-antihistamines in 95.67% (95% CI, 92.47% to 97.54%; I2 = 38%) of patients and omalizumab in 5.95% (95% CI , 2.55% to 13.27%; I2 = 83%) of patients. The pooled prevalence of anaphylaxis among patients with cold urticaria was 21.49% (95% CI, 15.79% to 28.54%; I2 = 69%). CONCLUSIONS: Cold urticaria constitutes an appreciable proportion of CIndU and CU cases and is predominantly managed with H1-antihistamines; few patients receive omalizumab. Anaphylaxis is common, and an epinephrine autoinjector prescription may be considered.

Chinese version of the chronic urticaria quality of life questionnaire: cultural adaptation, factor analysis, assessment of reliability and validity.

Chronic urticaria is a common skin disorder that contributes profound impact on patients' quality of life (QoL). However, the cause of the disease is not clear, and the treatment still faces challenges. To better evaluate the effectiveness of treatment, an effective questionnaire survey on quality of life is needed. For the first time in Italy, a new questionnaire for chronic spontaneous urticaria, the chronic urticaria quality of life questionnaire (CU-Q2oL), has been developed. The purpose of this study was to develop and verify the Chinese version of the chronic urticaria quality of life questionnaire (CU-Q2oL). Three hundred and twenty-eight chronic urticaria patients were prospectively recruited and evaluated by the translated Chinese version of CU-Q2oL along with the Dermatology Life Quality Index (DLQI). Factor analysis, internal consistency, convergent validity, sensitivity to change and known-group validity were determined. Multiple linear regressions were used to determine the predicting factors of CU-Q2oL results. Factor analysis revealed a six-dimensional structure, and five of the six scales showed good internal consistency. Convergent validity and know-group validity showed good correlations. It was found to distinguish well between patients with different levels of urticaria activity and those to be sensitive to change in the Chinese CU-Q2oL. Disease severity was highly significantly predictive of the CU-Q2oL score on all scales. The CU-Q2oL Chinese version is a valid, reliable and sensitive instrument. It can be widely adopted to evaluate treatment outcomes and be applied in clinical research in Chinese patients.

Global Epidemiology of Urticaria: Increasing Burden among Children, Females and Low-income Regions.

Urticaria has a high socioeconomic burden worldwide. However, the global epidemiology of urticaria and its geographical and temporal trends are not well studied. Using the Global Burden of Disease dataset, the aim of this study was to analyse the age-standardized prevalence, incidence, years lived with disability, and mean duration of urticaria in 195 countries from 1990 to 2017. In addition, the relationship between socioeconomic development and urticaria was evaluat-ed. The global prevalence of urticaria in 2017 was 86 million people. Females and children aged 1-4 years were more commonly affected than males and adults, respectively: these differences were outside the 95% uncertainty intervals. Regression analyses show-ed that a lower gross domestic product per capita was associated with a higher prevalence and incidence of urticaria (p < 0.001). The global prevalence of urticaria, incidence, and years lived with disability have remained stable from 1990 to 2017.

Analysis of the long-term economic burden of omalizumab on patients with chronic spontaneous urticaria.

Omalizumab (OMA) is highly effective for refractory chronic spontaneous urticaria (CSU), but its high cost exerts a great economic burden on patients and society. Current knowledge is lacking regarding the economic impact of long-term administration of OMA on patients with CSU in the real-world setting. We retrospectively investigated drug costs relevant to CSU treatment during the period before through to 12 months after starting OMA in actual clinical practice. This study involved 32 patients who received at least two injections of OMA (300 mg/4 weeks) and achieved good responses of urticaria control test score of 12 or more and/or weekly urticaria activity score of 6 or less within 12 weeks. Median drug costs of the overall patient cohort increased from ¥14 496/month to ¥104 522 after starting OMA, but reduced to ¥48 810 in 12 months along with reduced amount of OMA administration and concomitant medication use. In patients pretreated with antihistamine alone or plus alternative medicines such as H2 blocker and antileukotriene prior to OMA, the increased drug costs by adding OMA decreased to approximately 30% in 12 months mainly due to the OMA dose reduction and interval extension of OMA. The drug cost reduction was also observed in patients pretreated with intensive multi-agents, due to discontinuation of expensive immunosuppressants. In conclusion, the introduction of OMA significantly increased the total drug costs relevant to CSU management, but the costs decreased to half in 12 months, along with dose-reduced and interval-extended OMA and discontinued concomitant drugs in patients with CSU who responded well to OMA.

Estimated Frequency of Psychodermatologic Conditions in Alberta, Canada.

BACKGROUND: Psychodermatologic disorders are difficult to identify and treat. Knowledge about the prevalence of these conditions in dermatological practice in Canada is scarce. This hampers our ability to address potential gaps and establish optimal care pathways. OBJECTIVES: To provide an estimate of the frequencies of psychodermatologic conditions in dermatological practice in Alberta, Canada. METHODS: Two administrative provincial databases were used to estimate the prevalence of potential psychodermatological conditions in Alberta from 2014 to 2018. Province-wide dermatology claims data were examined to extract relevant International Classification of Disease codes as available. Claims were linked with pharmacy dispensation data to identify patients who received at least 1 psychoactive medication within 90 days of the dermatology claim. RESULTS: Of 243 963 patients identified, 28.6% had received at least 1 psychotropic medication (mean age: 47.9 years; 67.5% female). Rates of concurrent psychotropic medications were highest for pruritus and related conditions (46.7%), followed by urticaria (44.5%) and hyperhidrosis (32.8%). Among patients with psychotropic medications, rates of antidepressants were highest (56.3%), followed by anxiolytics (37.1%). Across billing codes, besides hyperhidrosis (71.2%), diseases of hair (61.4%) and psoriasis (59.1%) had the highest rates of antidepressant dispensations. Patients with atopic dermatitis had the highest rates for anxiolytic prescriptions (54.3%). CONCLUSION: In a 5-year window, more than a quarter of the identified dermatology patients in Alberta received at least 1 psychotropic medication, pointing to high rates of potential psychodermatologic conditions and/or concurrent mental health issues in dermatology. Diagnostic and care pathways should include a multidisciplinary approach to better identify and treat these conditions.

Assessment of ED triage of anaphylaxis patients based on the Emergency Severity Index.

OBJECTIVES: To describe the emergency department (ED) triage of anaphylaxis patients based on the Emergency Severity Index (ESI), assess the association between ESI triage level and ED epinephrine administration, and determine characteristics associated with lower acuity triage ESI assignment (levels 3 and 4). METHODS: We conducted a cohort study of adult and pediatric anaphylaxis patients between September 2010 and September 2018 at an academic ED. Patient characteristics and management were compared between Emergency Severity Index (ESI) triage level 1 or 2 versus levels 3 or 4 using logistic regression analysis. We adhered to STROBE reporting guidelines. RESULTS: A total of 1090 patient visits were included. There were 26 (2%), 515 (47%), 489 (45%), and 60 (6%) visits that were assigned an ESI triage level of 1, 2, 3, and 4, respectively. Epinephrine was administered in the ED to 53% of patients triaged ESI level 1 or 2 and to 40% of patients triaged ESI level 3 or 4. Patients who were assigned a lower acuity ESI level of 3 or 4 had a longer median time from ED arrival to epinephrine administration compared to those with a higher acuity ESI level of 1 or 2 (28 min compared to 13 min, p < .001). A lower acuity ESI level was more likely to be assigned to visits with a chief concern of hives, rash, or pruritus (OR 2.33 [95% CI, 1.20-4.53]) and less likely to be assigned to visits among adults (OR, 0.43 [0.31-0.60]), patients who received epinephrine from emergency medical services (OR 0.56 [0.38-0.82]), presented with posterior pharyngeal or uvular angioedema (OR, 0.56 [0.38-0.82]), hypoxemia (OR, 0.34 [0.18-0.64]), or increased heart (OR 0.83 [0.73-0.95]) or respiratory (OR 0.70 [0.60-0.82]) rates. CONCLUSION: Patients triaged to lower acuity ESI levels experienced delays in ED epinephrine administration. Adult and pediatric patients with skin-related chief concerns were more likely to be to be assigned lower acuity ESI levels. Further studies are needed to identify interventions that will improve ED anaphylaxis triage.

Chronic spontaneous urticaria in clinical practice: a pilot survey about attitudes and perceptions on assessment, diagnostic work-up and dietary management.

BACKGROUND: Chronic spontaneous urticaria (CSU) is a heterogeneous condition whose management can be complex and challenging. The aim of this study is to evaluate physicians' attitudes regarding practical aspects of CSU management, including adherence to international guidelines, criteria and instruments for CSU assessment, prescription of laboratory investigations and role of dietary measures. METHODS: A cross-sectional survey was conducted using a study-specific questionnaire. It was administered to a group of physicians with a specialist interest in CSU from different areas of Italy definable as "CSU experts" (group A; N.=21) and subsequently to other physicians who managed CSU only occasionally in their clinical activity (group B; N.=25). RESULTS: The EAACI/GA2LEN/EDF/WAO guidelines were considered very or moderately useful by the majority of participants. Significantly more physicians in group A reported that such guidelines were always followed in clinical practice (P=0.0008). Instruments for the assessment of CSU severity/activity and quality of life were used in clinical practice significantly more often by CSU experts as compared to group B. Dietary measures were frequently suggested for CSU patients by nearly three quarters of group B members and by only 5% of CSU experts (P<0.00001). When physicians were asked to indicate the type of laboratory examinations that were commonly performed in patients with longstanding and/or uncontrolled CSU, regardless of history, the investigations most frequently reported were full blood count and thyroid autoantibodies, followed by erythrocyte sedimentation rate and/or C-reactive protein and thyroid function tests. CONCLUSIONS: The results of the present pilot survey seem to suggest the heterogeneity of the approaches used for CSU management in clinical practice.

Clinical and laboratory assessment for the inflammation role in chronic spontaneous urticaria: A clinical study.

Chronic spontaneous urticaria (CSU) is triggered by unknown causes. We would like to explore the possible effect of hemogram parameters and several biochemical markers on CSU presence and also the severity of the disease. We also aimed to discuss the relationship between CSU and inflammation associated with these values. The study was planned prospectively. We selected patients already diagnosed with CSU who applied to the dermatology outpatient clinic and healthy controls. The patients and the healthy controls were tested for complete blood count, neutrophil/lymphocytes ratio and platelets/lymphocytes ratio, erythrocyte sedimentation rate, C-reactive protein, serum albumin and total bilirubin and indirect bilirubin levels. Urticaria activity score over 7 days (UAS-7) was calculated for the CSU patients. Forty patients with CSU and 55 healthy subjects were included in the study. Mean white blood cell (WBC) count is 8.37 ± 2.14 in the patients' group and 7.41 ± 2.01 in the healthy subjects group. Mean neutrophil (NEU) count is 4.88 ± 1.65 in the patients' group and 4.19 ± 1.39 in the healthy subjects group. Mean platelets (PLT) count is 308.48 ± 88.32 in the patients' group and 268.65 ± 64.80 in the healthy subjects group. We also detected positive correlations between UAS-7 score-WBC counts and UAS-7 score-NEU counts. Future studies are needed to investigate this possible relationship and confirm these results.