Real-world effectiveness of abrocitinib treatment in patients with difficult-to-treat atopic dermatitis

Background: Abrocitinib is a JAK-1 selective inhibitor registered for the treatment of moderate-to-severe atopic dermatitis (AD). Although efficacy and safety have been shown in phase 3 clinical trials, data on real-world patients with a treatment history of advanced systemics are scarce. Objectives:The objective of the study was to evaluate the effectiveness and safety of abrocitinib treatment in patients with difficult-to-treat AD in daily practice. Methods: In this prospective observational single-centre study, all AD patients who started abrocitinib treatment in the context of standard care between April 2021 and December 2022 were included. Effectiveness was assessed using clinician- and patient-reported outcome measures. Adverse events were evaluated. Results: Forty-one patients were included. The majority (n = 30; 73.2%) had failed (ineffectiveness) on other targeted therapies, including JAK inhibitors (n = 14, 34%) and biologics (n = 16, 39%). Abrocitinib treatment resulted in a significant decrease in disease severity during a median follow-up period of 25 weeks (IQR 16–34). Median EASI score at baseline decreased from 14.7 (IQR 10.4–25.4) to 4.0 (IQR 1.6–11.4) at last review (p &lt; 0.001). Median NRS itch decreased from 7.0 (IQR 5–8) to 3.0 (IQR 1–2) at last review (p &lt; 0.001). The most frequently reported AEs included gastrointestinal symptoms (27.6%), acne (20.7%) and respiratory tract infections (17.2%). 16 (39%) patients discontinued abrocitinib treatment due to ineffectiveness, AEs or both (41.2%, 41.2% and 11.8%, respectively). Conclusion: Abrocitinib can be an effective treatment for patients with moderate-to-severe AD in daily practice, including non-responders to other targeted therapies.</p

Higher prevalence of dupilumab-induced ocular adverse events in atopic dermatitis compared to asthma:A daily practice analysis

Background: Dupilumab has been shown to be an effective treatment in moderate-to-severe atopic dermatitis (AD) and severe asthma (SA). However, comparative real-world analyses of adverse events (AE), particularly dupilumab-associated ocular surface disease (DAOSD), are lacking. Objective: This is the first real-world study to provide insight into the prevalence of AEs associated with dupilumab in AD compared with SA. Secondary objectives were to assess the prevalence, onset and therapeutic strategies of DAOSD and evaluate dupilumab discontinuation rates. Methods: Data from two daily practice registries including AD and SA patients receiving dupilumab treatment were analyzed. Adverse events, including DAOSD, were evaluated. Results: In total, 322 AD and 148 SA patients were included. Headaches (23.6%), injection site reactions (10.1%), and influenza-like symptoms (13.5%) were more prevalent in SA patients. Interestingly, ocular AEs were significantly more prevalent in AD patients (62.1%, p &lt; 0.001), including conjunctivitis (17.1%, p = 0.004). 88% AD and 47% SA patients with ocular AEs received one or more ophthalmic treatment(s). Additionally, 20% of AD and 17.6% of SA patients discontinued dupilumab treatment due to ocular AEs, while only 65% of these AD and none of these SA patients were referred to an ophthalmologist. Conclusion: The higher incidence of DAOSD in AD patients compared with SA patients in this real-world study highlights the importance of physician awareness, especially when prescribing dupilumab to AD patients. Conversely, the findings of this study help alleviate potential concerns about ocular AEs in patients with SA who do not have comorbid AD. Furthermore, the effective management of most ocular AEs with ophthalmic treatments suggests favorable tolerability of dupilumab in daily practice, and multidisciplinary collaboration is essential to proactively manage ocular AEs before discontinuing dupilumab.</p

A nationwide study of the incidence and trends of first and multiple basal cell carcinomas in the Netherlands and prediction of future incidence*

Background: Basal cell carcinoma (BCC) is the most frequently diagnosed malignancy worldwide and an ever increasing annual incidence is observed. However, nationwide registries of BCCs are very rare, and often extrapolation of the data has been necessary to estimate the absolute number of diagnoses. As of September 2016, all histopathologically confirmed BCCs are registered in the Netherlands, due to developments in automatic notification and import in the Netherlands Cancer Registry. This offers the unique possibility to assess the nationwide population-based incidence of first and multiple BCCs. Objectives: To assess the nationwide incidence and trends of first and multiple BCCs in the Netherlands and to predict incidence rates up to 2029. Methods: All patients with histopathologically confirmed BCC between 2001 and 2019 were selected from the population-based Netherlands Cancer Registry. Age-standardized incidence rates were calculated and trends were analysed with use of the estimated annual percentage change. Prediction of BCC incidence rates up to 2029 was based on a regression model. Results: In total, 601 806 patients were diagnosed with a first BCC over the period 2001–2019. The age-standardized incidence rates for both men and women with a first BCC increased over these years, from 157 to 304 and from 124 to 274 per 100 000 person-years, respectively. For male and female patients aged 30–39 years, decreases in annual incidences of −3·6% and −3·0%, respectively, were found in recent years. For patients aged 50 years or older an ever increasing trend was found. One-quarter of the patients with a first primary BCC developed one or more subsequent BCCs within 3 years. Increases in incidence of 30·4% (male) and 25·3% (female) are expected in the next 10 years. Conclusions: BCC incidence has doubled over the past two decades. Trends have seemed to stabilize in recent years for patients aged < 50 years. This might be a first sign of a decreasing trend. The incidence continues to rise in patients aged 50 years and older. In the next decade a further increase in BCC incidence is expected

The impact of the COVID-19 pandemic on keratinocyte carcinoma in the Netherlands: Trends in diagnoses and magnitude of diagnostic delays

Background: The COVID-19 pandemic impacted Dutch society and the healthcare system. Focus switched to care for COVID-19 patients, thereby altering care for non-COVID patients. Non-urgent medical visits were cancelled or postponed and patients were reluctant to visit healthcare services. Objectives: This study aimed to investigate the impact of the COVID-19 pandemic on trends in diagnoses of keratinocyte carcinoma (cutaneous squamous cell carcinoma (cSCC), basal cell carcinoma (BCC)) and to assess the magnitude of diagnostic delays. Methods: The number of cSCC and BCC diagnoses in each month of 2020 was compared to the expected number of diagnoses for these months, using data from the Netherlands Cancer Registry. Expected diagnoses for 2020 were used as a reference to take the yearly increase in keratinocyte carcinoma incidence into account and were calculated by extrapolating the trends observed in 2017–2019. Comparisons were further stratified by age, sex and region. Estimates of diagnostic delays were calculated and corrected for the influence of excess mortality due to the pandemic on keratinocyte carcinoma incidence. Results: The number of cSCC and BCC diagnoses substantially decreased when compared to the number of diagnoses expected from March to May 2020 (cSCC −29%, BCC −50%). These decreases were observed across all age groups, both sexes, and all regions. From June to September the number of cSCC and BCC diagnoses was higher than expected, after which it slightly dropped below expected in October to December. In total, 2020 keratinocyte carcinoma diagnoses continued to trail those expected, with a backlog of around 1150 cSCCs and 11 767 BCCs remaining at the end of the year. Conclusion: Diagnosis of keratinocyte carcinoma was suboptimal during the COVID-19 pandemic, due to diagnostic delays likely resulting from both patient and health system-related delay. Further studies will need to determine the effects of these diagnostic delays on outcomes

Using a Clinicopathologic and Gene Expression (CP-GEP) Model to Identify Stage I–II Melanoma Patients at Risk of Disease Relapse

Background: The current standard of care for patients without sentinel node (SN) metastasis (i.e., stage I–II melanoma) is watchful waiting, while >40% of patients with stage IB–IIC will eventually present with disease recurrence or die as a result of melanoma. With the prospect of adjuvant therapeutic options for patients with a negative SN, we assessed the performance of a clinicopathologic and gene expression (CP-GEP) model, a model originally developed to predict SN metastasis, to identify patients with stage I–II melanoma at risk of disease relapse. Methods: This study included patients with cutaneous melanoma ≥18 years of age with a negative SN between October 2006 and December 2017 at the Sahlgrenska University Hospital (Sweden) and Erasmus MC Cancer Institute (the Netherlands). According to the CP-GEP model, which can be applied to the primary melanoma tissue, the patients were stratified into high or low risk of recurrence. The primary aim was to assess the 5-year recurrence-free survival (RFS) of low-and high-risk CP-GEP. A secondary aim was to compare the CP-GEP model with the EORTC nomogram, a model based on clinicopathological variables only. Results: In total, 535 patients (stage I–II) were included. CP-GEP stratification among these patients resulted in a 5-year RFS of 92.9% (95% confidence interval (CI): 86.4–96.4) in CP-GEP low-risk patients (n = 122) versus 80.7% (95%CI: 76.3–84.3) in CP-GEP high-risk patients (n = 413; hazard ratio 2.93 (95%CI: 1.41–6.09), p < 0.004). According to the EORTC nomogram, 25% of the patients were classified as having a ‘low risk’ of recurrence (96.8% 5-year RFS (95%CI 91.6–98.8), n = 130), 49% as ‘intermediate risk’ (88.4% 5-year RFS (95%CI 83.6–91.8), n = 261), and 26% as ‘high risk’ (61.1% 5-year RFS (95%CI 51.9–69.1), n = 137). Conclusion: In these two independent European cohorts, the CP-GEP model was able to stratify patients with stage I–II melanoma into two groups differentiated by RFS

Efficacy, cost-minimization, and budget impact of a personalized discharge letter for basal cell carcinoma patients to reduce low-value follow-up care

Background The incidence of keratinocyte carcinomas is high and rapidly growing. Approximately 80% of keratinocyte carcinomas consist of basal cell carcinomas (BCC) with 50% of these being considered as low-risk tumors. Nevertheless, 83% of the low-risk BCC patients were found to receive more follow-up care than recommended according to the Dutch BCC guideline, which is one visit post-treatment for this group. More efficient management could reduce unnecessary follow-up care and related costs. Objectives To study the efficacy, cost-utility, and budget impact of a personalized discharge letter for low-risk BCC patients compared with usual care (no personalized letter). Methods In a multi-center intervention study, a personalized discharge letter in addition to usual care was compared to usual care in first-time BCC patients. Model-based cost-utility and budget impact analyses were conducted, using individual patient data gathered via surveys. The outcome measures were number of follow-up visits, costs and quality adjusted life years (QALY) per patient. Results A total of 473 first-time BCC patients were recruited. The personalized discharge letter decreased the number of follow-up visits by 14.8% in the first year. The incremental costs after five years were -24.45 per patient. The QALYs were 4.12 after five years and very similar in both groups. The national budget impact was -2,7 million after five years. Conclusions The distribution of a personalized discharge letter decreases the number of unnecessary follow-up visits and implementing the intervention in a large eligible population would results in substantial cost savings, contributing to restraining the growing BCC costs

Publisher Correction: Novel pleiotropic risk loci for melanoma and nevus density implicate multiple biological pathways

Correction to: Nature Communications; https://doi.org/10.1038/s41467-018-06649-5; published online: 14 November 201