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Atopic dermatitis (AD) is a common chronic skin disease. Only relatively scant studies from Asian countries have attempted to quantify AD-associated healthcare utilization and costs by using population-based databases. This study aims to evaluate the AD-associated annual healthcare utilization and costs in Taiwan.A retrospective matched-cohort study was conducted by matching the AD cases with controls at a 1:4 (cases:controls) ratio, with the data for both the cases and controls being sourced from the 2017 National Health Insurance Research Database (NHIRD). The AD patients were stratified by disease severity based on their treatments. Differences in the regression-adjusted frequency of care and costs between the cases and controls were compared using t-tests by the severity level of AD.The incremental frequency of outpatient visits per year increased with AD severity (9.60, 11.28, and 16.23 for mild, moderate, and severe cases, respectively). However, the frequency of inpatient care and emergency room visits per year showed no consistent pattern associated with disease severity. The incremental total costs per year were NT$9,511.64, NT$9,705.20, and NT$15,762.09 for mild, moderate, and severe cases, respectively, and the outpatient and drug costs accounted for 46.65%-54.82% and 17.01%-31.20% of the total costs, respectively.AD was found to impose significant healthcare costs, with estimated total cost burdens of NT$3.61 billion in 2017, which is 0.314% of Taiwan's national health expenditure and 0.020% of Taiwan's gross domestic product.

The objective of this study was to conduct a retrospective analysis to understand the patient profile, treatment patterns, healthcare resource utilization, and cost of atopic dermatitis (AD) of patients eligible for targeted therapy in Taiwan.A retrospective, claims-based analysis was undertaken using Taiwan's National Health Insurance Research Database from 01 January 2014 to 31 December 2017. Patients aged ≥ 2 years and with at least one diagnosis code for AD during 2015 were identified. Patients with comorbid autoimmune diseases were excluded. Enrolled AD patients were categorized using claims-based treatment algorithms by disease severity and their eligibility for targeted therapy treatment. A cohort of targeted therapy-eligible patients was formed, and a matched cohort using patients not eligible for targeted therapy was derived using propensity score matching based on age, gender, and the Charlson Comorbidity Index (CCI). Treatment patterns, resource utilization, and costs were measured during a 1-year follow-up period.A total of 377,423 patients with AD were identified for this study. Most patients had mild AD (84.5%; n = 318,830) with 11.9% (n = 45,035) having moderate AD, and 3.6% (n = 13,558) having severe AD. Within the 58,593 moderate-to-severe AD patients, 1.5% (n = 897) were included in the targeted therapy-eligible cohort. The matched cohort consisted of 3558 patients. During the 1-year follow-up period, targeted therapy-eligible patients utilized antihistamines (85.5%), topical treatments (80.8%), and systemic anti-inflammatories (91.6%) including systemic corticosteroids (51.4%) and azathioprine (59.1%). During the first year of follow-up, targeted therapy-eligible patients (70.5%; 7.01 [SD = 8.84] visits) had higher resource utilization rates and frequency of AD-related outpatient visits compared with the matched cohort (40.80%; 1.85 [SD = 4.71] visits). Average all-cause direct costs during 1-year follow-up were $2850 (SD = 3629) and $1841 (SD = 6434) for the eligible targeted therapy and matched cohorts, respectively. AD-related costs were 17.7% ($506) of total costs for the targeted therapy eligible cohort and 2.2% ($41) for the matched cohort.AD patients eligible for targeted therapy in Taiwan experienced high resource and economic burden compared with their non-targeted-therapy-eligible counterparts.

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are frequently associated with dermatologic adverse events (dAEs), having great impacts on patients' health-related quality of life (HRQoL) and treatment adherence. We aimed to examine the association between various dAEs and HRQoL in patients treated with EGFR-TKI therapy.This was a cross-sectional study including 132 non-small-cell lung cancer (NSCLC) patients treated with gefitinib, erlotinib, afatinib, or osimertinib in Taiwan. The severity level of dAEs was graded by NCI-CTCAE v4.03 and PRO-CTCAE ITEMS v1.0. All participants answered the Functional Assessment of Cancer Therapy-Epidermal Growth Factor Receptor Inhibitors (FACT-EGFRI-18) HRQoL questionnaire.The clinician-reported severity of pruritus, photosensitivity, alopecia, and Karnofsky performance status was associated with HRQoL (β = - 6.773, p = 0.046; β = - 5.250, p = 0.032; β = - 8.121, p = 0.001; β = 0.327, p = 0.002; respectively). The clinician-reported severity of all dAEs except paronychia had negative correlations with HRQoL. The symptom gradings of CTCAE and PRO-CTCAE had positive correlation.The severity of pruritus, photosensitivity, and alopecia was associated with HRQoL of patients receiving EGFR-TKI therapy. Using patient-reported outcome measurements helps clinicians to capture the actual impact of symptoms on physical, social-emotional, and functional well-being.

Cutaneous adverse drug reactions are undesirable cutaneous changes caused by medications. Drug eruptions can mimic a wide range of dermatoses that include exanthematous (morbilliform), urticarial, pustular, bullous, papulosquamous, or granulomatous lesions, and sometimes these eruptions may present with annular, polycyclic, or polymorphous configurations. The correct identification of a cutaneous drug eruption depends on a high index of suspicion, detailed medication exposure history, chronologic evaluation of the causal relationships between drug exposures and eruptions, and the exclusion of other infectious or idiopathic diseases. Most drug eruptions are annoying but self-limited, usually resolving after the withdrawal of the causative agents. Rarely, patients have severe cutaneous adverse reactions, such as Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms (DRESS), which are potentially lethal adverse drug reactions that involve the skin and mucous membranes and may also damage internal organs. Prompt recognition of the alarming signs of severe cutaneous adverse reactions and providing adequate treatment may thus be life-saving. We present the main clinical presentations, histopathology, possible implicated medications, and treatment of cutaneous adverse drug reactions that can present in annular configurations.

Background/purpose Taiwan Drug-Injury Relief System (TDRS) has been implemented since 1999. More than 60% of the approved applications were associated with severe cutaneous adverse reactions (SCARs). Studies assessing SCARs using real-world evidence are very limited. TDRS offers abundant case information as a source of real-world evidence to investigate the characteristics of SCARs in Taiwan. The purpose of this study is to understand the trends and characteristics of SCARs in Taiwan. Methods Applications from Drug-Injury Relief Database (TDRD) from 1999 to 2016 were retrospectively analyzed. Results A declining trend in SCARs application was noticed after 2012, and 952 applications of SCARs were identified. The most common subtypes of SCARs were SJS/TEN (n = 455/206), DRESS (n = 228), GBFDE (n = 34) and AGEP (n = 18). The most common culprit drugs were allopurinol, carbamazepine, phenytoin, diclofenac and lamotrigine for SJS/TEN; allopurinol, phenytoin, co-trimoxazole, carbamazepine and phenobarbital for DRESS; mefenamic acid for GBFDE; non-steroidal anti-inflammatory drugs (NSAIDs) and beta-lactam antibacterials for AGEP. The proportions of mortality cases were 28.9% for SJS/TEN; 36% for DRESS; 11.8% for GBFDE and 5.6% for AGEP. The mean latent period of SJS/TEN, DRESS, GBFDE and AGEP were 21.8 days, 29.2 days, 3.3 days and 6.7 days, respectively. Conclusions The approved drug-injury relief applications associated with SCARs were mainly SJS, TEN and DRESS. The most common culprit drugs were antiepileptics, antibacterials, antigout agents, and NSAIDs. The latent periods showed some distinct features for different types of SCARs. In light of the high mortality rate, public awareness and vigilance of SCARs are crucial for the patient safety.

Rituximab is a potential initial adjuvant therapy for bullous pemphigoid, yet clinical experience is scarce.We aimed to examine the clinical outcomes and safety of initial combination therapy with systemic corticosteroids and adjuvant rituximab for the treatment of bullous pemphigoid.A retrospective cohort study was performed on 84 patients with bullous pemphigoid, who received systemic corticosteroids with or without initial adjuvant rituximab therapy (defined as rituximab use within 12 weeks after initiation of systemic corticosteroids).Among the 84 patients included (37 received systemic corticosteroids with rituximab and 47 were treated with systemic corticosteroids without rituximab), the median time to complete remission on minimal therapy or off therapy was 215 days (95% confidence interval 176.9-253.1) in patients receiving rituximab vs 529 days (95% confidence interval 338.6-719.4) in those not receiving rituximab. A Cox regression analysis showed an increased probability of reaching complete remission on minimal therapy or off therapy with the combined therapy (hazard ratio = 2.28 [1.28-4.07], p = 0.005) after age, Bullous Pemphigoid Disease Activity Index score, and underlying diseases were controlled. In multivariate logistic/linear regressions, initial adjuvant rituximab therapy was associated with a higher complete remission rate (odds ratio = 6.63 [2.09-21.03]) and lower cumulative prednisolone (mg)/body weight (kg) (B = -24.86 [-44.06 to -8.29]) within 48 weeks. Risk of hospitalization for infection was not elevated in the group treated with adjuvant rituximab.Rituximab use as adjuvant therapy within 12 weeks after initiation of systemic corticosteroids was associated with a faster and higher rate of achieving complete remission on minimal therapy or off therapy, as well as a significant corticosteroid-sparing effect and a comparable safety profile in this retrospective study. Hence, initial combination therapy with corticosteroids and adjuvant rituximab could serve as an effective treatment option for bullous pemphigoid, but this requires confirmation in randomized controlled studies.

Shannaz Nadia Yusharyahya,1 Valdi Ven Japranata,2 Ratih Wulan Kusumahapsari,2 Lili Legiawati,1 Rinadewi Astriningrum,1 Karin Rachmani,1 Chia-Yu Chu3 1Department of Dermatology and Venereology, Faculty of Medicine, Universitas Indonesia - Dr. Cipto Mangunkusumo Hospital, Jakarta Pusat, Indonesia; 2Faculty of Medicine, Universitas Indonesia, Jakarta Pusat, Indonesia; 3Department of Dermatology, National Taiwan University and Taiwan University College of Medicine, Taipei City, TaiwanCorrespondence: Shannaz Nadia Yusharyahya, Department of Dermatology and Venereology, Faculty of Medicine, Universitas Indonesia - Dr. Cipto Mangunkusumo Hospital, Jalan Diponegoro Nomor 71, Kenari, Senen, Jakarta Pusat, Indonesia, 10430, Tel/Fax +62 21 31935383, Email nadiayusharyahya@yahoo.comBackground/Purpose: COVID-19 pandemic has compromised healthcare services in dermatology and venereology. Given such circumstances, studies investigating the consultation pattern of related fields in hospitals were relatively scarce. The present study aimed to delineate such matter from tertiary hospital viewpoint.Methods: Details concerning referred patients from the emergency room, inpatient wards, intensive care unit, and nursery to the Department of Dermatology and Venereology, Dr. Cipto Mangunkusumo Hospital were retrospectively collected from electronic health records. Cases admitted in the 17 months span before and during COVID-19 global outbreak were included. The obtained data were presented descriptively, and Chi-squared test was performed upon attributes of interest at a significance level of 0.05.Results: A slight increase of total consultation was found in the COVID-19 era with an initial reduction at the beginning (April–May 2020). One-time consultation was the most inquired to our department in both periods of which dermatitis was the most prevalent case and Gram staining was the most common examination. Topical antibiotics and emollient were the most prescribed medications before and during the outbreak, respectively. The conformity of initial-final decision, appropriateness of initial-final diagnosis, and consult response time were significantly different (p < 0.05) between the two groups.Conclusion: There were changes of the number of consultation requests in the pandemic era with statistically significant change of decision conformity, diagnoses, appropriateness, and consult response time. Although some changes appeared, the most prevalent diagnoses remained.Keywords: consultation pattern, COVID-19, dermatology, venereology

Hypoxia-inducible factor-1α (HIF-1α) is widely considered to be one of the key regulators of tumor angiogenesis. The upstream regulation is complex and involves several growth factors, cytokines, and hypoxia. Herein, we have identified miR-519c as a hypoxia-independent regulator of HIF-1α, acting through direct binding to the HIF-1α 3′ untranslated region and leading to reduced tumor angiogenesis. Overexpression of miR-519c resulted in a significant decrease of HIF-1α protein levels and reduced the tube formation of human umbilical vein endothelial cells; similarly, antagomir inhibition of miR-519c increased the level of HIF-1α protein and enhanced angiogenic activity, suggesting an important role of miR-519c in HIF-1α–mediated angiogenesis. Consistent with the overexpression of miR-519c in cancer patients with better prognosis, mice injected with miR-519c–overexpressing cells exhibited dramatically reduced HIF-1α levels, followed by suppressed tumor angiogenesis, growth, and metastasis. In addition, we found that hepatocyte growth factor (HGF), a known HIF-1α inducer, reduced the miR-519c levels through an Akt-dependent pathway. This regulation was posttranscriptional and may be mediated by suppression of miR-519c maturation. Taken together, our findings provide the first evidence that miR-519c is a pivotal regulator of tumor angiogenesis and that microenvironmental HGF contributes to regulating miR-519c biogenesis in cancer cells. Cancer Res; 70(7); 2675–85

Supplementary Figures 1-7 from MicroRNA-519c Suppresses Hypoxia-Inducible Factor-1α Expression and Tumor Angiogenesis

Background: In JADE COMPARE, abrocitinib improved severity of atopic dermatitis (AD) and demonstrated rapid itch relief. Objectives: We examined clinically meaningful improvements in selected patient-reported outcomes (PROs). Methods: JADE COMPARE was a multicentre, phase 3 randomized, double-blind, placebo-controlled trial. Adults with moderate-to-severe AD were randomized 2:2:2:1 to receive 16 weeks of oral abrocitinib 200 or 100 mg once daily, dupilumab 300 mg subcutaneous injection every 2 weeks, or placebo, with background topical therapy. PROs included Dermatology Life Quality Index (DLQI), Patient-Oriented Eczema Measure (POEM), Night Time Itch Scale (NTIS), Pruritus and Symptoms Assessment for Atopic Dermatitis, Patient Global Assessment, SCORing Atopic Dermatitis, and Hospital Anxiety and Depression Scale. Results: At week 16, the proportion of patients achieving POEM scores

The efficacy and safety of dupilumab have been reported previously based on data from controlled clinical trials. The GLOBOSTAD study extends the scope of these trials by providing real-world data. This analysis reports baseline demographics and family disease history in patients with atopic dermatitis (AD) who received treatment with dupilumab in a real-world setting. This 5-year, international, multicentre, non-interventional study (GLOBOSTAD; NCT03992417) included patients ≥12 years old with moderate-to-severe AD (Investigator’s Global Assessment score ≥3) who received dupilumab treatment based on country-specific prescribing criteria. Data reported are for the population at baseline (N = 952; data cut-off: March 2022) in 22 countries. In the 952 patients included at baseline, mean (standard deviation) age at AD onset was 11.1 (16.0) years. Male patients represented 57.8% of patients and White patients 65.2%. The majority of patients were enrolled from Italy (17.2%), Japan (12.4%) and Spain (11.3%). Family history of type 2 inflammatory conditions (number of patients [%]) was prevalent, including AD (364 [38.2%]), asthma (238 [25%]), allergic rhinitis (219 [23%]), food allergies (74 [7.8%]), recurrent or chronic urticaria (31 [3.3%]), nasal polyposis (21 [2.2%]), eosinophilic esophagitis (11 [1.2%]) and other atopic/allergic conditions (39 [4.1%]). Most cases of type 2 inflammatory conditions were reported in first-degree relatives. Most patients enrolled in the GLOBOSTAD study developed AD during pre-adolescence. Family history of select type 2 inflammatory conditions, including AD, asthma and allergic rhinitis, was present in a moderate proportion of patients.

Most advanced non-small-cell lung cancer (NSCLC) patients received targeted therapies of epidermal growth factor receptor tyrosine kinase inhibitors. However, few studies reported the relationships between adverse events (AEs) and psychological distress.The aims of this study were to (1) examine the differences in the incidence of AEs, fear of progression (FoP), anxiety, and depression among 3 generations of epidermal growth factor receptor tyrosine kinase inhibitors (first, gefitinib and erlotinib; second, afatinib; third, osimertinib) and (2) examine the difference in levels of FoP, anxiety, and depression between the presence and absence of AEs in NSCLC patients.This study used a cross-sectional study design. Patients with NSCLC (N = 120) were recruited from a medical center in northern Taiwan. Adverse events, FoP, anxiety, and depression were assessed by questionnaires.The incidence rates of photosensitivity, mouth and throat sores, and diarrhea were significantly high in the gefitinib, erlotinib, and afatinib groups, respectively. A lesser proportion of patients experienced AEs in the osimertinib group, compared with those in the gefitinib and erlotinib, and afatinib groups. The incidence rates of FoP, anxiety, and depression were 13.8% to 26.0%, 24.1% to 40.4%, and 17.6% to 40.0%, respectively. Patients with photosensitivity, paronychia, and alopecia had significantly higher levels of FoP, anxiety, and depression.This study confirmed the priorities of care among 3 generations of epidermal growth factor receptor tyrosine kinase inhibitors in NSCLC patients, using both the Common Terminology Criteria for Adverse Events (CTCAE 4.03) and PRO-CTCAE 1.0. Photosensitivity, paronychia, and alopecia were associated with higher levels of FoP, anxiety, and depression. Therefore, these AEs require further management.Our study suggests a follow-up to address AEs and psychological distress.

Background Supportive care is the cornerstone of management of adult and paediatric Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). However, consensus on the modalities of supportive care is lacking.Objectives Our aim in this international multicentric Delphi exercise was to establish a multidisciplinary expert consensus to standardize recommendations regarding supportive care in the acute phase of SJS/TEN.Methods Participants were sent a survey via the online tool SurveyMonkey, consisting of 103 statements organized into 11 topics: multidisciplinary team composition, suspect drug management, infection prevention, fluid resuscitation and prevention of hypothermia, nutritional support, pain and psychological distress management, management of acute respiratory failure, local skincare, ophthalmological management, management of other mucosa, and additional measures. Participants evaluated the level of appropriateness of each statement on a scale of 1 (extremely inappropriate) to 9 (extremely appropriate). The results were analysed according to the RAND/UCLA Appropriateness Method.Results Forty-five participants from 13 countries (on three continents) participated. After the first round, a consensus was obtained for 82.5% of the 103 initially proposed statements. After the second round, a final consensus was obtained for 102 statements.Conclusions We have reached an international Delphi-based consensus on best supportive care practice for SJS/TEN. Our expert consensus should help guide physicians in treating patients with SJS/TEN and thereby improve short-term prognosis and the risk of sequelae.

Background Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are used as the standard first-line treatment for patients with advanced EGFR-mutated non-small cell lung cancer (NSCLC). However, the impact of clinical factors, including comorbidities and treatment-related adverse events (AEs), on quality of life (QoL) was seldom investigated. Objective We aimed to investigate the association of comorbidities, AEs, and QoL in treatment-naïve advanced NSCLC patients receiving EGFR-TKI treatments. Methods A multi-center prospective observational study was conducted to evaluate QoL and AEs at baseline, the 2nd, 4th, 12th, and 24th week. Clinical characteristics, comorbidities, and pre-treatment laboratory data were recorded. QoL was assessed by using the summary score of the EORTC QLQ-C30 and the dermatology life quality index. The impact of comorbidities, neutrophil-to-lymphocyte ratio (NLR), and AEs on QoL was analyzed by generalized estimating equations. Results A total of 121 patients were enrolled. Diarrhea (p = 0.033), anorexia (p p = 0.017) were significantly associated with a QoL impairment. Among skin toxicities, acneiform rash (p = 0.002), pruritus (p = 0.002), visual analogue scale for pruritus (≥ 3 and p = 0.006; ≥7, p = 0.001) and pain (1–3, p = 0.041) were associated with a QoL impairment. No significant association was found between comorbidities and QoL changes. Conclusion Diarrhea, anorexia, skin pain, and pruritus may cause a deterioration in QoL. NLR may be a potential predictive factor for QoL impairment. Aggressive management and close monitoring are crucial to improve QoL in patients receiving EGFR-TKI therapy.

To determine phenotype-related dupilumab response in adult patients with atopic dermatitis (AD), this multicenter, retrospective study included 111 adults with moderate-to-severe AD in Taiwan, with median age of 31.5 years (18–87) and 71 (64.0%) males. Patients received dupilumab 300 mg per two to three weeks up to 12 months. We found a significant improvement after 4 and 16 weeks of treatment in all patients for all the assessed scores, including eczema area and severity index (EASI) improvement ≥50% (EASI-50) and 75% (EASI-75), EASI reaching minimal clinically important difference (MCID), and Investigator’s Global Assessment (IGA) improvement ≥2. Importantly, prior to asthma, early AD onset and 3-week drug intervals were significantly associated with a high proportion of EASI-75 at month 12, while prurigo and lichenoid phenotypes were associated with a lower proportion of EASI-75 at month 12. However, the majority of adverse events were mild in severity. In conclusion, our study results identify phenotype-related dupilumab response at month 12 in adults with moderate-to-severe AD, and we suggest that treatment should not be discontinued until reaching a satisfactory clinical response.

Over the last 2 decades, omalizumab is the only anti-IgE antibody that has been approved for asthma and chronic spontaneous urticaria (CSU). Ligelizumab, a higher-affinity anti-IgE mAb and the only rival viable candidate in late-stage clinical trials, showed anti-CSU efficacy superior to that of omalizumab in phase IIb but not in phase III. This report features the antigenic-functional characteristics of UB-221, an anti-IgE mAb of a newer class that is distinct from omalizumab and ligelizumab. UB-221, in free form, bound abundantly to CD23-occupied IgE and, in oligomeric mAb-IgE complex forms, freely engaged CD23, while ligelizumab reacted limitedly and omalizumab stayed inert toward CD23; these observations are consistent with UB-221 outperforming ligelizumab and omalizumab in CD23-mediated downregulation of IgE production. UB-221 bound IgE with a strong affinity to prevent FcԑRI-mediated basophil activation and degranulation, exhibiting superior IgE-neutralizing activity to that of omalizumab. UB-221 and ligelizumab bound cellular IgE and effectively neutralized IgE in sera of patients with atopic dermatitis with equal strength, while omalizumab lagged behind. A single UB-221 dose administered to cynomolgus macaques and human IgE (ε, κ)-knockin mice could induce rapid, pronounced serum-IgE reduction. A single UB-221 dose administered to patients with CSU in a first-in-human trial exhibited durable disease symptom relief in parallel with a rapid reduction in serum free-IgE level.

Background The common contact allergens may change over time as the environmental exposure changes. Objectives To identify the prevalence rates and changing trends of contact allergens in Taiwan over a 40-year period. Materials & methods The patch testing results of a referral centre from 1978 to 2018 were retrospectively reviewed. The study population was divided into four groups according to 10-year intervals. The prevalence rates of contact sensitization to each agent and the clinical relevance were analysed. For patients with positive reactions to relevant allergens, the occupations and sites of dermatitis were analysed. Results From 1978 to 2018, a total of 4005 patients underwent patch testing. Successively increasing trends of positive reactions to cobalt, fragrance mix I, and para-phenylenediamine (PPD) were found. Methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) was an emerging contact allergen. Hairdressers, cosmetologists, and aromatherapists became the occupations most commonly having positive reactions in the most recent 10 years. In the first two decades, the face and neck were the most commonly affected areas. Later, hands became the most commonly affected sites. Conclusions The prevalence rates of positive reactions to cobalt, fragrance mix I, and PPD increased successively. MCI/MI was an emerging contact allergen of special concern.

Background: Ligelizumab, a next-generation, humanized anti-immunoglobulin E (IgE) monoclonal antibody is in development as a treatment for patients with chronic spontaneous urticaria, whose symptoms are inadequately controlled with standard-of-care therapy. Objective: To evaluate the long-term safety and re-treatment efficacy of ligelizumab 240 mg in patients who completed the core study and extension study. Methods: This open-label, single-arm, long-term Phase 2b extension study was designed to assess patients who were previously administered various doses of ligelizumab, omalizumab or placebo in the Phase 2b, dose-finding core study and who presented with active disease after Week 32. In the extension study, patients received ligelizumab 240 mg subcutaneously every 4 weeks, for 52 weeks and were monitored post-treatment for 48 weeks. Results: Overall, ligelizumab was well-tolerated with no newly identified safety signals. A total of 95.4% (226/237) screened patients received ligelizumab 240 mg in the extension study; 84.1% (190/226) of patients experienced at least one treatment-emergent adverse event. Most reported events were mild (41.6%) or moderate (35.8%) and mostly unrelated to the study treatment. At Week 12, 46.5% of patients had a complete response increasing to 53.1% after 52 weeks. Following 52 weeks of extension study treatment, 75.8% (95% confidence interval, 69.9, 81.3) of patients had cumulative complete responses. The median time to relapse in complete responders was 38 weeks. Conclusion: The long-term safety profile of ligelizumab 240 mg in patients with chronic spontaneous urticaria was consistent with the core study and re-treatment efficacy was shown. Trial registration: ClinicalTrials.gov Identifier: NCT02477332 and NCT02649218.

Although evidence showing that Staphylococcus aureus (S. aureus) is directly causative of atopic dermatitis (AD) is still lacking, there is evidence that S. aureus abundance is associated with disease flares and therapeutic responses. Patients receiving ATx201 OINTMENT 2% twice-daily had a significant reduction in the abundance of S. aureus and increasing Shannon diversity of skin microbiome compared to vehicle after seven days. A small molecule with a narrow-spectrum effect, especially on S. aureus, might be an attractive alternative for the treatment of AD.

Background: Atopic dermatitis has been linked to increased risk of many comorbidities. However, the risks of certain comorbidities are still debated. Objective: To better characterize the basic demographics, treatment patterns, and associations between atopic dermatitis and comorbidities and to further investigate the influence of severity on comorbidities. Methods: We used a sample cohort of 999,992 people from the National Health Insurance Research Database of Taiwan to evaluate atopic dermatitis in the general population. Results: A total of 12,780 patients with atopic dermatitis in 2010 were identified. The prevalence was 1.28%. The proportions of severe and moderate cases were 7.43% and 19.26%, respectively. The most commonly used systemic treatment was corticosteroids. Compared with the general population, atopic dermatitis patients showed increased risks of all 9 groups of comorbidities, including autoimmune disorders, atopic disorders, chronic urticaria, ocular disorders, metabolic disorders, hypertensive disorders, ischemic heart disorders, cerebrovascular disorders, and psychiatric disorders. The severity and persistence of atopic dermatitis were correlated with the development of certain comorbidities. Limitations: Miscoding and misclassification might have occurred, and only patients with active disease were enrolled. Conclusion: Patients with atopic dermatitis have higher risks of various comorbidities. Comprehensive monitoring and treatment plans are needed to better manage these patients.

Atopic dermatitis (AD) is generally considered a T helper type 2-dominated disease. Pediatric AD is usually less severe than adult AD, but it may present as moderate to severe lesions that are inadequately managed by current modalities including emollients/moisturizers, topical corticosteroids (TCSs), topical calcineurin inhibitors (TCIs), and even systemic immunosuppressants (such as cyclosporine, azathioprine, methotrexate, and mycophenolate mofetil). In addition, systemic immunosuppressants are often not recommended for childhood AD by the current guidelines due to their toxicities. Therefore, there is still an unmet need for a safe and effective long-term therapy for pediatric AD patients whose disease is inadequately controlled or who are intolerant to current treatments. The emerging therapeutics for AD focuses on intervening in the inflammatory pathway by targeting specific cytokines/chemokines or their receptors. Monoclonal antibodies against immunoglobulin E (IgE), interleukin (IL)-4 receptor subunit α, IL-5, IL-13, IL-31 receptor subunit α, IL-33, and thymic stromal lymphopoietin (TSLP) have been evaluated clinically for AD. Encouraging results have been reported for many of the biologics, of which the most exciting is dupilumab. Other emerging systemic therapies include small molecules such as baricitinib, abrocitinib, upadacitinib, and tradipitant. Several novel topical agents are under clinical investigation for the treatment of AD, including topical phosphodiesterase 4 (PDE4) inhibitors, Janus kinase (JAK) inhibitors, aryl hydrocarbon receptor (AhR) modulating agents, and transient receptor potential vanilloid subfamily member 1 (TRPV1) antagonists. Accompanied by thorough characterization of different phenotype and endotype subsets, the application of precision medicine could provide new prospects for the optimal treatment of AD.

Drug eruptions are among the great masqueraders that sometimes cause diagnostic challenges in clinical practice. Pharmacologic agents may induce skin changes, sharing the same pathophysiologic mechanisms of specific dermatoses, or inducing drug eruptions with different pathologic mechanisms that have similar clinical presentations. The former conditions are usually called drug-induced skin diseases, whereas the latter conditions are termed "dermatosis-like drug eruptions." Both types are great imitators in dermatologic practice and can be easily misdiagnosed as other diseases or lead to unrecognized causative agents.

Epidermal growth factor receptor (EGFR) inhibitors are selective and effective treatments for cancers with relevant mutations. Purpuric drug eruptions are an uncommon but clinically significant dermatological side effect related to EGFR inhibitor use that are associated with positive bacterial cultures and responsive to antibiotic treatment. However, the longitudinal temporal shifts in the skin microbiome that occur before and after antibiotic treatment of purpuric drug eruptions remain largely unknown.To characterize temporal changes in the skin and mucosal microbiomes before and after antibiotic treatment of EGFR inhibitor-related purpuric drug eruptions.Twelve patients who experienced EGFR inhibitor-related purpuric drug eruptions were recruited from a dermato-oncology clinic in Taiwan from May 2017 to April 2018. Swabs were obtained from skin lesions and the nasal mucosa before and after antibiotic treatment of purpuric drug eruptions. After the amplification and sequencing of bacterial 16S rRNA genes, the diversity and compositions of microbiomes sampled at different time points were compared.The alpha diversity (represented by the Shannon index) of the skin microbiome increased significantly in the recovered phase of purpuric drug eruptions compared with that of the active phase. By contrast, the nasal microbiome showed no significant change in alpha diversity. The relative abundance of Staphylococcus significantly decreased in samples from skin of the recovered phase, which was confirmed by analysis of compositions of microbiomes (ANCOM) and the ALDEx2 analysis packages in R.The cutaneous microbiome of purpuric drug eruptions showed a significant increase in alpha diversity and a decrease in the relative abundance of Staphylococcus following antibiotic treatment. These findings may help guide antimicrobial therapy of this EGFR inhibitor-related condition.

Chronic pruritus is an unpleasant sensory perception that negatively affects quality of life and is common among patients with type 2 diabetes mellitus. Current antipruritic therapies are insufficiently effective. Thus, the mediation of diabetic pruritus by histamine-independent pathways is likely. The aim of this study was to identify possible mediators responsible for diabetic pruritus. A total of 87 patients with type 2 diabetes mellitus were analysed, of whom 59 had pruritus and 28 did not. The 2 groups were assessed for baseline demographics, serum biochemistry parameters, cytokines, and chemokines. This study also investigated the associations of these factors with the severity of itching. Neither haemoglobin A1c nor serum creatinine levels were correlated with severity of itching. Significantly higher levels of interleukin-4 (p = 0.004), interleukin-13 (p = 0.006), granulocyte-macrophage colony-stimulating factor (p

Atopic dermatitis is a prevalent inflammatory skin disease that manifests clinically as pruritus and eczema. Severe forms of atopic dermatitis can be chronic and relapsing or associated with other dermatological complications and comorbidities, resulting in lifelong impacts across multiple aspects for patients. This study was conducted to calculate the atopic dermatitis-related economic burden in Taiwan. First, the out-of- pocket costs incurred by 200 patients with atopic dermatitis were estimated using a specifically designed questionnaire. Secondly, work impairment was converted into quantifiable costs. The costs reimbursed by the Taiwan National Health Insurance (NHI), which were estimated in our previous work, were included in the final calculation. The atopic dermatitis-related economic burden for patients in Taiwan in 2018 was estimated as (2018 New Taiwan dollars; NT$) 37.90 billion, which is 0.207% of Taiwan’s gross domestic product. This substantial economic burden suggests an existing need for more effective and equitable treatment for atopic dermatitis.

Limited studies on atopic dermatitis (AD) have investigated the possible covariance of sociodemographic factors with the Hospital Anxiety and Depression Scale (HADS).This study aimed to examine the possible covariance between AD severity and HADS scores of patients in Taiwan.Patients with AD from a medical center and 2 regional hospitals in Taiwan were enrolled in this cross-sectional study from April 2018 to April 2019. AD severity was measured using the "scoring atopic dermatitis" index, and anxiety and depression were screened based on HADS.A total of 200 patients were included. After correcting for sociodemographic variables, significantly more borderline (≥8) and abnormal (≥11) cases of anxiety/depression (First, the cross-sectional study design cannot show causality. Second, baseline data, including a history of underlying cancer or previous psychiatric disorder, were not obtained in the questionnaire and may confound the HADS scores. Finally, a standardized psychiatric clinical interviews study design should be used for higher accuracy in the assessment of psycho-comorbidities.Higher anxiety and depression risks were noted in patients with moderate-to-severe AD. Except for psychosomatic symptoms, all kinds of anxiety and depression symptoms occurred more frequently in patients with moderate-to-severe AD.

Atopic dermatitis (AD, also called atopic eczema) is a long-term skin disease that causes intensely itchy, red skin. Healthcare providers can prescribe medicated creams and ointments to reduce the signs and symptoms of AD. However, these treatments are not always enough to provide relief. A new medicine called abrocitinib, which is taken every day as a tablet, reduces part of the body’s immune response that happens in AD. The clinical study described in this plain language summary, called JADE COMPARE, investigated how well and how safely 16 weeks of treatment with abrocitinib worked in adults with AD compared to placebo (‘dummy treatment’) and a medicine that is already approved for AD, called dupilumab. The study showed that abrocitinib was better than placebo in improving the signs and symptoms of AD after 16 weeks. In addition, patients who were taking abrocitinib 200 mg for 2 weeks experienced greater relief from itch than patients who were taking abrocitinib 100 mg, placebo, or dupilumab. More people who took abrocitinib 200 mg reported side effects than those taking abrocitinib 100 mg, placebo, or dupilumab, but most of these side effects were mild or moderate. ClinicalTrials.gov NCT number: NCT03720470 .

Cutaneous immune-related adverse events are common in cancer patients receiving immunotherapies but seldom studied in a comprehensive way of collecting all cancer types with comparisons between different immune-oncology drugs and correlation to patient survival. In this retrospective cohort study, we recruited 468 cancer patients receiving immunotherapies in a tertiary referral center in Taiwan and try to determine real-world incidence of cutaneous immune-related adverse events and their associations with the survival rates. Among them, 128 patients (27.4%) had cutaneous immune-related adverse events, with maculopapular eruption (10.6%) and pruritus (10.1%) most frequently identified in the monotherapy group. The incidence of these cutaneous immune-related adverse events was highest in patients receiving pembrolizumab (34.1%, P P P

Atopic dermatitis has a substantial impact on work and activity impairment according to studies from Western communities. Prospective studies of work productivity and activity impairment in Asian patients with atopic dermatitis are lacking. The aims of this study were to investigate the impacts of atopic dermatitis on work productivity and activity impairment among Taiwanese patients, and to stratify the analyses by disease severity. One-third of employed participants reported missing work (absenteeism) in the preceding week due to atopic dermatitis, while 88.5% of the remaining two-thirds reported impaired work effectiveness (presenteeism). In addition, 92.5% of all participants reported impaired daily activities. Overall work impairment (aggregate productivity loss from absenteeism and presenteeism) was 1.8- and 2.6-fold greater in subjects with moderate and severe atopic dermatitis, respectively, compared with those with mild atopic dermatitis. Presenteeism, but not absenteeism, contributes to the majority of total work impairment in this cohort. Daily activity impairment was 1.5-fold greater in moderate atopic dermatitis, and 2.0-fold greater in severe atopic dermatitis, compared with mild atopic dermatitis. Both work and activity impairment showed significant positive correlations with atopic dermatitis severity scores (SCORing Atopic Dermatitis; SCORAD). In conclusion, work productivity and activity impairment is significantly correlated with disease severity in this Taiwanese atopic dermatitis cohort. In order to obtain a full picture of disease burden to patients and caregivers, patients with atopic dermatitis should be monitored for disease activity as well as corresponding impacts on quality of life.

Background/purpose: Rituximab is effective in treating pemphigus both as the first-line treatment and as an add-on treatment for refractory disease. A high rate of relapse among patients receiving rituximab means that maintenance therapy is frequently required. Therefore, we aimed to evaluate the use of azathioprine as maintenance therapy for patients receiving rituximab and to investigate the efficacy and safety of one or multiple cycles of rituximab treatment. Methods: We retrospectively collected data regarding pemphigus patients treated with rituximab from 2008 to 2015 with at least one year of follow-up at a referral center in Northern Taiwan. The medical records and clinical data were reviewed to determine the efficacy and complication rate of the treatment. Results: A total of 78 pemphigus patients were identified. Ninety-one percent of the patients achieved complete remission after the first cycle of rituximab with a relapse rate of 67.9%. Repeated cycles of rituximab showed a trend to shorten the time to next complete remission and to reduce the rate of subsequent relapses. The adverse events were usually not severe and were manageable. Use of azathioprine significantly prolonged the duration of remission (21.98 ± 16.24 vs. 9.98 ± 7.93 months, P = 0.0232). This effect of azathioprine usage remained after univariate and multivariate logistic regressions. Conclusion: This study provides an insight that azathioprine could serve as a good choice of maintenance therapy for patients receiving rituximab. The efficacy and safety of rituximab remain favorable even with repeated administration. Keywords: Azathioprine, Maintenance, Pemphigus, Rituximab

Background: In the majority of patients with chronic spontaneous urticaria, most currently available therapies do not result in complete symptom control. Ligelizumab is a next-generation high-affinity humanized monoclonal anti-IgE antibody. Data are limited regarding the dose-response relationship of ligelizumab and the efficacy and safety of ligelizumab as compared with omalizumab and placebo in patients who have moderate-to-severe chronic spontaneous urticaria that is inadequately controlled with H1-antihistamines at approved or increased doses, alone or in combination with H2-antihistamines or leukotriene-receptor antagonists. Methods: In a phase 2b dose-finding trial, we randomly assigned patients to receive ligelizumab at a dose of 24 mg, 72 mg, or 240 mg, omalizumab at a dose of 300 mg, or placebo, administered subcutaneously every 4 weeks for a period of 20 weeks, or a single 120-mg dose of ligelizumab. Disease symptoms of hives, itch, and angioedema were monitored by means of weekly activity scores. The main objective was to determine a dose-response relationship for the complete control of hives (indicated by a weekly hives-severity score of 0, on a scale from 0 to 21, with higher scores indicating greater severity); the primary end point of this response was assessed at week 12. Complete symptom control was indicated by a weekly urticaria activity score of 0 (on a scale from 0 to 42, with higher scores indicating greater severity). Safety was analyzed throughout the trial. Results: A total of 382 patients underwent randomization. At week 12, a total of 30%, 51%, and 42% of the patients treated with 24 mg, 72 mg, and 240 mg, respectively, of ligelizumab had complete control of hives, as compared with 26% of the patients in the omalizumab group and no patients in the placebo group. A dose-response relationship was established. At week 12, a total of 30%, 44%, and 40% of the patients treated with 24 mg, 72 mg, and 240 mg, respectively, of ligelizumab had complete control of symptoms, as compared with 26% of the patients in the omalizumab group and no patients in the placebo group. In this small and short trial, no safety concerns regarding ligelizumab or omalizumab emerged. Conclusions: A higher percentage of patients had complete control of symptoms of chronic spontaneous urticaria with ligelizumab therapy of 72 mg or 240 mg than with omalizumab or placebo. (Funded by Novartis Pharma; ClinicalTrials.gov number, NCT02477332.).

Objective: To examine the difference in levels of fear of cancer progression (FoP), anxiety, depression between presence/absence of the target-adverse events (AEs); and to examine the differences in incidence rate of AEs and FoP, anxiety, and depression among three generations of EGFR-TKIs therapy (first, gefitinib and erlotinib [G1]; second, afatinib [G2]; third, osimertinib [G3]) in non-small-cell lung cancer (NSCLC) patients.Methods: A cross-sectional study design. NSCLC patients (n=128) were recruited from a medical center in Taiwan. A set of structured questionnaires assessing AEs, FoP, anxiety and depression. Results: Parts of AEs, such as photosensitivity, paronychia, and alopecia, exhibited significantly higher levels of FoP, anxiety, and depression. Less patients experienced AEs in the G3 group than those in the G1 or G2 group but still reported experiencing itching, dry skin with grade 3 severity. The incidence rates of mouth/throat sores, and cheilosis/cheilitis in the G2 group was significantly higher than those in the G1 or G3 group. The incidence rate of FoP, anxiety and depression were 13.8-26.3%, 23.8-40.4% and 16.7-42.1%, respectively.Conclusions: The priorities of care among three generations of EGFR-TKIs in patients with NSCLC were established. FoP, anxiety and depression were present among different targeted therapies and require further attention.

The oral Janus kinase 1 (JAK1) inhibitor abrocitinib, which reduces interleukin-4 and interleukin-13 signaling, is being investigated for the treatment of atopic dermatitis. Data from trials comparing JAK1 inhibitors with monoclonal antibodies, such as dupilumab, that block interleukin-4 receptors are limited.In a phase 3, double-blind trial, we randomly assigned patients with atopic dermatitis that was unresponsive to topical agents or that warranted systemic therapy (in a 2:2:2:1 ratio) to receive 200 mg or 100 mg of abrocitinib orally once daily, 300 mg of dupilumab subcutaneously every other week (after a loading dose of 600 mg), or placebo; all the patients received topical therapy. The primary end points were an Investigator's Global Assessment (IGA) response (defined as a score of 0 [clear] or 1 [almost clear] on the IGA [scores range from 0 to 4], with an improvement of ≥2 points from baseline) and an Eczema Area and Severity Index-75 (EASI-75) response (defined as ≥75% improvement from baseline in the score on the EASI [scores range from 0 to 72]) at week 12. The key secondary end points were itch response (defined as an improvement of ≥4 points in the score on the Peak Pruritus Numerical Rating Scale [scores range from 0 to 10]) at week 2 and IGA and EASI-75 responses at week 16.A total of 838 patients underwent randomization; 226 patients were assigned to the 200-mg abrocitinib group, 238 to the 100-mg abrocitinib group, 243 to the dupilumab group, and 131 to the placebo group. An IGA response at week 12 was observed in 48.4% of patients in the 200-mg abrocitinib group, 36.6% in the 100-mg abrocitinib group, 36.5% in the dupilumab group, and 14.0% in the placebo group (P0.001 for both abrocitinib doses vs. placebo); an EASI-75 response at week 12 was observed in 70.3%, 58.7%, 58.1%, and 27.1%, respectively (P0.001 for both abrocitinib doses vs. placebo). The 200-mg dose, but not the 100-mg dose, of abrocitinib was superior to dupilumab with respect to itch response at week 2. Neither abrocitinib dose differed significantly from dupilumab with respect to most other key secondary end-point comparisons at week 16. Nausea occurred in 11.1% of the patients in the 200-mg abrocitinib group and 4.2% of those in the 100-mg abrocitinib group, and acne occurred in 6.6% and 2.9%, respectively.In this trial, abrocitinib at a dose of either 200 mg or 100 mg once daily resulted in significantly greater reductions in signs and symptoms of moderate-to-severe atopic dermatitis than placebo at weeks 12 and 16. The 200-mg dose, but not the 100-mg dose, of abrocitinib was superior to dupilumab with respect to itch response at week 2. Neither abrocitinib dose differed significantly from dupilumab with respect to most other key secondary end-point comparisons at week 16. (Funded by Pfizer; JADE COMPARE ClinicalTrials.gov number, NCT03720470.).