Rates Of Non-melanoma Skin Cancer Research Articles

Analysis of Prevalence, Socioeconomic and Disease Trends of Non-Melanoma Skin Cancer in New Zealand from 2008 to 2022

BackgroundSkin cancer shows geographic and ethnic variation. New Zealand—with a predominantly fair-skinned populations, high UV indices and outdoor lifestyles—has high rates of skin cancer. However, population prevalence data is lacking. This study aimed to determine the demographics and socioeconomic disease trends of non-melanoma skin cancer prevalence in New Zealand from a large targeted-screening study.MethodsA targeted screening programme was conducted among 32,839 individuals, Fitzpatrick Skin Types I to IV in Auckland, New Zealand during the 2008–2022 period. This data was analyzed retrospectively. Linear regression models were used to assess statistical trends of skin cancer prevalence over time, along with associated factors that included demographics, disease trends and overall prevalence.ResultsA total of 32,839 individuals were screened and 11,625 skin cancers were detected. 16,784 individuals were females who had 4,378 skin cancers. 16,055 individuals were males who had 5,777 skin cancers. 54 males and 65 females had multiple skin cancers. The article presents detailed descriptions of tumour types and subtypes detected, age groups, demographic and socioeconomic information. regarding the non-melanoma skin cancers detected.ConclusionOverall men have more non-melanoma skin cancer (NMSC) than females; however females develop more BCC on the lips. BCC is three times more common in the 31-50 age group, whereas SCC are significantly more prevalent after age 80. Prevalence of BCC has not changed over the 15-year timeframe of the study but SCC has increased. Older ages and higher incomes are associated with higher rates of NMSC in New Zealand.

Safety Profile of Upadacitinib up to 5 Years in Psoriatic Arthritis, Ankylosing Spondylitis, and Non-radiographic Axial Spondyloarthritis: An Integrated Analysis of Clinical Trials.

This integrated analysis of the phase 2/3 and phase 3 SELECT trials describes the safety profile of upadacitinib, an oral Janus kinase inhibitor, for up to 5years of exposure across psoriatic arthritis (PsA), ankylosing spondylitis (AS), and non-radiographic axial spondyloarthritis (nr-axSpA) (including pooled axial spondyloarthritis [axSpA]). Safety data from five trials of upadacitinib in PsA (2 trials), AS (2 trials), and nr-axSpA (1 trial) were analyzed up to a data cut-off of August 15, 2022. One PsA study included adalimumab as an active comparator. Treatment-emergent adverse events (TEAEs) were summarized for PsA (pooled upadacitinib 15mg once daily and adalimumab 40mg biweekly), AS (pooled upadacitinib 15mg), nr-axSpA (upadacitinib 15mg), and pooled axSpA (pooled upadacitinib 15mg from axSpA trials). TEAEs were reported as exposure-adjusted event rates per 100 patient-years (E/100 PY). A total of 1789 patients (PsA, n = 907; AS, n = 596; nr-axSpA, n = 286) received ≥ 1 dose of upadacitinib 15mg for 3689 PY of exposure or adalimumab (n = 429) for 1147 PY of exposure. Overall TEAEs and serious TEAEs were highest in PsA and numerically higher with upadacitinib versus adalimumab; rates were similar between AS and nr-axSpA. In PsA, higher rates of serious infection, herpes zoster (HZ), lymphopenia, and nonmelanoma skin cancer (NMSC) were observed with upadacitinib versus adalimumab. Rates of malignancy excluding NMSC, adjudicated major adverse cardiovascular events, and adjudicated venous thromboembolic events were comparable between upadacitinib and adalimumab in PsA and were similar across diseases. Higher rates of serious infection, HZ, lymphopenia, and NMSC were observed with upadacitinib versus adalimumab in PsA; slightly elevated rates for most of these TEAEs were seen with upadacitinib in PsA versus axSpA. Upadacitinib 15mg demonstrated a generally consistent safety profile across disease states with no new safety signals identified. SELECT-AXIS 1: NCT03178487; SELECT-AXIS 2: NCT04169373; SELECT-PsA 1: NCT03104400; SELECT-PsA 2: NCT03104374.

A randomized trial of a wearable UV dosimeter for skin cancer prevention.

Non-melanoma skin cancer (NMSC) is the most prevalent cancer in the United States. Despite guidelines on ultraviolet (UV) avoidance, it remains difficult for people to assess their exposure, as UV is invisible and the onset of UV-induced symptoms is delayed. In a prospective randomized trial, 97 elderly patients with a history of actinic keratoses (AK) were followed over 6 months. Fifty patients received UV counseling from a dermatologist and a wearable UV dosimeter that provided real-time and cumulative UV exposure. Forty-seven patients received only UV counseling from a dermatologist. Over 75% of participants recorded UV exposure at least once a week during the summer. After 6 months of intervention, when comparing the device group to the control group, we observed a non-significant 20% lower ratio of incidence rates of AKs (95% CI = [-41, 55%], p-value = 0.44) and a significant 95% lower ratio of incidence rates of NMSCs (95% CI = [33, 99.6%], p-value = 0.024). Surveys demonstrated that the control group's score in self-perceived ability to participate in social activities significantly increased by 1.2 (p-value = 0.04), while in the device group, this score non-significantly decreased by 0.9 (p-value = 0.1). We did not observe changes, or between-group differences, in anxiety and depression surveys. This pilot clinical trial has a short duration and a small sample size. However, device adherence and quality of life questionnaires suggest a smartphone-connected wearable UV dosimeter is well accepted by an elderly population. This trial also indicates that a wearable UV dosimeter may be an effective behavioral change tool to reduce NMSC incidence in an elderly population with a prior history of AKs.Clinical trial registration: clinicaltrials.gov, identifier NCT03315286.

Incidence of Nonmelanoma Skin Cancers in Alberta, Canada, From 2007 to 2018.

Nonmelanoma skin cancer (NMSC) is the most common malignancy affecting Caucasian populations and has been seeing steady increases in incidence globally for decades. Our previous study (from Alberta, Canada) had shown a plateau in the incidence rates for NMSC. This contrasts with data from other regions within Canada and throughout the world that indicated a continued increase in incidence rates of NMSCs. The objective of this study was to provide an update on the trends in incidence of NMSC in Alberta, Canada, from 2007 to 2018. A retrospective analysis of patients from Alberta diagnosed with NMSC from 2007 to 2018 inclusive was conducted with data retrieved from Alberta Cancer Registry. Sex-, age-, anatomical location-, NMSC subtype-, stage-specific incidence rates and trends were examined. From 2007 to 2018, overall incidence rates of NMSC increased by 36%. Invasive squamous cell carcinoma (SCC) and in situ SCC demonstrated the most significant increase, invasive SCC [annual percentage change (APC) 3.48, P = .014] and in situ SCC (APC 5.61, P = .0001). In addition, we were able to determine that females had the most significant increases in NMSC incidence rates from 2007 to 2018 particularly invasive SCC (APC 3.03, P = <.0001) and in situ SCC (APC 5.08, P = <.0001). After initial levelling of NMSC incidence in Alberta in the early part of 21st century, the incidence of NMSC continues to increase over the past decade. The reasons for this change are not clear and likely multifactorial.

Prevalence of Second Cancers in Patients with Polycythemia Vera (PV): A Retrospective Analysis of US Real-World Claims Data

Background:Polycythemia vera (PV) is a chronic myeloproliferative neoplasm (MPN) associated with risk of leukemic or fibrotic progression (Tefferi and Barbui. Am J Hematol. 2017;92;94-108). In addition to the known risk of disease transformation, patients with MPNs have a 60% higher risk of developing second non-hematologic cancers compared to matched controls. Skin cancers are among the most prevalent second cancers, with a reported 2.8-fold increase in risk of non-melanoma skin cancer (NMSC) (Landtblom et al., Leukemia. 2018;32:2203-10). The inherent risk associated with MPNs is exacerbated by cytoreductive treatments, as patients treated with hydroxyurea (HU) were found to have a two-fold higher risk of NMSC compared to patients who were not treated with HU (Barbui et al., Leukemia. 2019;33:1996-2005). Previous studies examined fewer than 2000 patients; the study populations may have included patients with other MPNs and PV. Our objective was to evaluate the frequency of second cancers in patients with a primary PV diagnosis who were treated with HU compared to phlebotomy only using a large US real-world claims database. Methods:This real-world, retrospective cohort study used Optum's deidentified Market Clarity Data consisting of electronic health records (EHR) on 105 million US patients and linked medical and prescription claims between 1/1/2007 to 12/31/2019. More than 82,000 patients with ≥1 PV diagnosis at any time were identified within the extracted dataset. For this analysis, eligible patients were ≥18 years old and required ≥2 PV diagnosis codes with ≥60 days between the first and last diagnosis code in the data period. Patients were indexed at the first diagnosis code of PV preceded by ≥1 year of EHR data (“index”) and required ≥1 year of post-index data or death prior to data period end. Patients with a pre-index diagnosis of secondary polycythemia, leukemia, myelodysplastic syndrome, myelofibrosis, or stem cell transplant were excluded. Second cancers were identified at first occurrence of a diagnosis code for a defined cancer in EHR during specified time periods. Analysis of post-treatment cancer rates used a subset of patients with pre-index medication data and excluded cancer types identified prior to treatment. Results:The total study cohort included 20,089 patients with PV (mean age, 63.0 years; 57.8% male; 88.6% Caucasian). Some patients (15.5%; n=3112) had evidence of a pre-index cancer. Median duration of follow-up was 4.3 years (IQR, 2.4-5.9). Among the total cohort, 35.7% (7181 patients) reported at least one second cancer in the post-index period (“post-index period prevalence”). The rate of second cancers in the post-index period was 109.7 events per 1000 patient years (PY). The most common non-hematologic malignancies were skin cancers (22.1/1000 PY) followed by prostate cancer (8.1/1000 PY) and breast cancer (6.7/1000 PY) (Figure 1). Within the total cohort, 9.1% (1830 patients) reported at least one skin cancer in the post-index period, with 8.3% (1659 patients) experiencing NMSC and 1.4% (286 patients) experiencing melanoma (Figure 1). The post-index period prevalence rate of NMSC was 6 times higher vs. the rate of melanoma (19.8 vs. 3.3/1000 PY). Among NMSCs, the rate of basal cell carcinoma was higher than the rate of squamous cell carcinoma (8.7 vs. 6.9/1000 PY). However, the highest rate was observed for non-specific or unspecified malignant neoplasms (8.9/1000 PY). Within a subset of 17,402 patients with pre-index medication data, 20.2% (n=3512) were exposed to at least 4 weeks of HU (without ruxolitinib) at any time; 19.0% (n=3314) were treated with phlebotomy (PHL) only. The rate of any second malignancy subsequent to treatment was &amp;gt;2.5-times higher in the HU vs. PHL group (140.4 vs. 55.3/1000 PY) (Table 1). Rates of skin cancers were nearly two times higher in the HU vs. PHL group for any skin cancer (31.6 vs. 17.7/1000 PY), NMSC (28.9 vs. 15.7/1000 PY), and melanoma (4.5 vs. 2.9/1000 PY). Conclusion:To our knowledge, this is the largest retrospective study evaluating the frequency of second cancers in a cohort of US patients with PV to-date. We found that patients with PV had high rates of malignancies associated with their primary PV diagnosis. The highest rates were observed for skin cancers, driven by the frequency of NMSC. Patients treated with HU had nearly twice the rate of skin cancers (including NMSC and melanoma) compared to PHL-only treated patients.

Malignancy in the Upadacitinib Clinical Trials for Rheumatoid Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis, and Non-radiographic Axial Spondyloarthritis.

This article aims to describe malignancies in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), or non-radiographic axial spondyloarthritis (nr-axSpA) treated with upadacitinib (UPA) or active comparators. This integrated safety analysis includes data from 11 phase3 UPA trials across RA (6 trials), PsA (2 trials), AS (2 trials; one phase2b/3), and nr-axSpA (1 trial). Treatment-emergent adverse events (TEAEs) were summarized for RA (pooled UPA 15mg [UPA15], pooled UPA 30mg [UPA30], adalimumab 40mg [ADA], methotrexate monotherapy [MTX]), PsA (pooled UPA15, pooled UPA30, ADA), AS (pooled UPA15), and nr-axSpA (UPA15). TEAEs were reported as exposure-adjusted event rates (events/100 patient-years). Median treatment duration ranged from 1.0 to 4.0years (with a maximum of 6.6years in RA). Across treatments and indications, rates of malignancy excluding nonmelanoma skin cancer (NMSC) ranged from 0.2 to 1.1, while NMSC ranged from 0.0 to 1.4. In RA, rates of malignancy excluding NMSC were generally similar between UPA15, UPA30, ADA, and MTX (breast and lung cancer were the most common). In RA and PsA, Kaplan-Meier analyses revealed no differences in event onset of malignancy excluding NMSC with UPA15 versus UPA30 over time. In RA, NMSC rates were higher with UPA30 than UPA15; both UPA15 and UPA30 were higher than ADA and MTX. In PsA, rates of malignancy excluding NMSC and NMSC were generally similar between UPA15, UPA30, and ADA. In AS and nr-axSpA, malignancies were reported infrequently. Few events of lymphoma were reported across the clinical programs. Rates of malignancy excluding NMSC were generally similar between UPA15, UPA30, ADA, and MTX and were consistent across RA, PsA, AS, and nr-axSpA. A dose-dependent increased rate of NMSC was observed with UPA in RA. ClinicaTrials.gov identifier: NCT02706873, NCT02675426, NCT02629159, NCT02706951, NCT02706847, NCT03086343, NCT03104400, NCT03104374, NCT03178487, and NCT04169373.

Image-Guided Superficial Radiation Therapy Has Superior 2-Year Recurrence Rates to Mohs Micrographic Surgery

Non-melanoma skin cancers (NMSCs) are the most common malignancy in the USA, and incidence is rising. Mohs micrographic surgery (MMS) is a tissue-sparing surgical technique often used in NMSCs. Superficial radiation therapy (SRT) was widely used prior to the advent of MMS, but MMS has superior recurrence rates and replaced SRT as a first-line therapy. Image-guided SRT (IGSRT) was invented in 2015 and utilizes ultrasound to improve SRT precision and produces minimal side effects (99% grade 1 or 2).[1] The hypothesis is that NMSCs treated with IGSRT will have improved 2-year recurrence rates of compared to those treated with Mohs micrographic surgery. This retrospective cohort study compared the 2-year recurrence probability of early stage NMSCs (squamous and basal cell carcinomas (SCCs and BCCs)) treated by IGSRT (2,286 lesions) to data on NMSCs treated by MMS (5,391 lesions) via one sample proportion tests. IGSRT-treated NMSC data is from a database published by Yu et al.[1] The 2-year recurrence probability statistical analysis is from McClure et al.[2] Medical Subject Headings were used to search PubMed for reports of 2-year recurrence rates of NMSCs treated by MMS. Seventeen studies were screened; 14 studies were excluded for lack of 2-year time to event analysis, or irrelevant patient population (non-BCC/SCC study, advanced disease), leaving 3 studies for comparison. IGSRT-treated NMSCs have a statistically significantly improved 2-year recurrence rates compared to MMS-treated (p<0.001 for pooled data). When separated by histology, 2-year recurrence rates of all reported SCCs and BCCs treated by MMS were also inferior to those treated by IGSRT, p<0.001, p = 0.0218, respectively. In this analysis, IGSRT has superior 2-year recurrence rates. Limitations include insufficient follow-up to report on the 5-year recurrence probability and inability to adjust for confounding factors beyond histology. This data implies that IGSRT is a well-tolerated, paradigm-shifting treatment option for patients with early stage NMSCs who cannot tolerate or refuse surgery. IGSRT provides patients the choice of treatment modality that best aligns with their goals of care.

Second primary malignancies in patients with lymphoma in Denmark after high-dose chemotherapy and autologous haematopoietic stem-cell transplantation: a population-based, retrospective cohort study

Second primary malignancies (SPMs) are known complications after chemotherapy, but the risk is not well characterised for patients with lymphoma treated with high-dose chemotherapy and autologous haematopoietic stem-cell transplantation (HSCT). We aimed to investigate the rate of SPMs in this population relative to matched control individuals from the general population. In this retrospective, population-based cohort study, patients aged 18 years or older with an aggressive lymphoma who received high-dose chemotherapy and autologous HSCT in Denmark between Jan 1, 2001, and Dec 31, 2017, were included from the Danish Lymphoma Registry and matched (1:5) to control individuals from the general population on birth year and sex via the Danish Civil Registration System. Patients were eligible if they had a registered date of autologous HSCT and patients with primary CNS lymphoma were excluded. Exclusion criteria for both patients and matched control individuals were HIV infection, organ transplantation, or other malignancies before inclusion. The key endpoint was the incidence of SPMs assessed in all study participants. The effect of treatment on SPMs was also investigated in patients who were followed up from first lymphoma diagnosis, with high-dose chemotherapy and autologous HSCT as a time-dependent exposure. Of 910 patients with lymphoma assessed, 803 were included (537 [67%] were male and 266 [33%] were female); 4015 matched control individuals were included (2685 [67%] were male and 1330 [33%] were female). Ethnicity data were not available. Median follow-up was 7·76 years (IQR 4·77-11·73). The SPM rate was higher among patients receiving high-dose chemotherapy and autologous HSCT than matched control individuals (adjusted hazard ratio [HR] 2·35, 95% CI 1·93-2·87, p<0·0001). Patients receiving high-dose chemotherapy and autologous HSCT had a higher rate of non-melanoma skin cancer (2·94, 2·10-4·11, p<0·0001) and of myelodysplastic syndrome or acute myeloid leukaemia (AML; 41·13, 15·77-107·30, p<0·0001) than matched control individuals, but there was no significant difference in the rate of solid tumours (1·21, 0·89-1·64, p=0·24). The cumulative risk of SPMs at 10 years was 20% (95% CI 17-23) in patients compared with 14% (13-15) in matched control individuals. High-dose chemotherapy and autologous HSCT was associated with an increased risk of SPMs when analysed as a time-dependent exposure from first lymphoma diagnosis (adjusted HR 1·58, 95% CI 1·14-2·17, p=0·0054). High-dose chemotherapy and autologous HSCT was associated with an increased risk of non-melanoma skin cancer and myelodysplastic syndrome or AML but not with increased risk of solid tumours in patients treated for lymphoma. These findings are relevant for future individualised risk-benefit assessments when choosing between high-dose chemotherapy and autologous HSCT and chimeric antigen receptor T-cell therapy in this setting. Danish Cancer Society.

Patient Perception of Skin Cancer Reduction by Nicotinamide Correlates With Use.

Introduction Nicotinamide (Vitamin B3) has been shown to reduce the rate of non-melanoma skin cancers by 23%, yet most patients do not know that this supplement reduces skin cancer. Understanding patient beliefs about skin cancer reduction attributed to nicotinamide is important to appropriately counsel patients on oral supplement use and ultimately to prevent non-melanoma skin cancers. Objective The objective of this study was to determine the association between nicotinamide use and perceived efficacy in skin cancer reduction. Methods Patients who underwent Mohs surgery in 2019 were sent an online survey assessing nicotinamide use, efficacy compared to sunscreen, and perceived skin cancer risk reduction. Results Data from 50 surveys revealed a perceived risk reduction attributed to nicotinamide of 31.2% for basal cell carcinoma (BCC), 30.2% for squamous cell carcinoma (SCC), and 24.3% for melanoma. In the subset of respondents taking nicotinamide, the perceived risk reduction was significantly higher at 41.2% for BCC and 38.3% for SCC (p<0.05) and positively correlated with reported nicotinamide use (p<0.05). The perceived risk reduction of melanoma was not significantly increased in patients taking nicotinamide (31.6%); however, the perceived risk reduction was correlated with nicotinamide use (p<0.05). In addition, 15.6% of respondents believed that nicotinamide was more effective than sunscreen at preventing skin cancer. Conclusion A larger perceived reduction of non-melanoma skin cancers attributed to nicotinamide is associated with increased oral nicotinamide use. Better patient education regarding the reduction of skin cancers with oral nicotinamide will need to be implemented to change patients' perceptions of the value of nicotinamide.

547 Evaluating the Excision and Diagnosis Rates of Non-Melanoma Skin Cancers in a Plastic Surgery Department

Abstract Aim Skin cancer is the most common cancer in the UK. 95% of complete excision is considered the national average and achieving this is important for our patients and our practice. The aims of our study were to evaluate our complete excision rates, sensitivity, and specificity in diagnosing and excising Non-Melanoma Skin Cancers (NMSC) as a department. Method We conducted a retrospective audit of adult patients undergoing excision of NMSC in our department in July 2022. Data was collected on age, gender, clinical and pathological diagnosis, surgeon grade, complications, site and subtype of lesion excised. Results Of the 100 cases identified, 43% of lesions excised were BCC and 22% were SCC. 72% of procedures were carried out by registrars. 98% of excisions were complete with 2 incomplete excisions and 13 excisions with narrow margins. 86% of specimens with narrow margins or incomplete excision were excised from craniofacial areas. Clinical diagnosis sensitivity for BCC was 79% and 86% for SCC, whereas specificity was 79% for BCC and 58% for SCC. The overall clinical diagnosis sensitivity for NMSC was 81% and negative predictive value was 88%. Conclusions Our complete excision rate and sensitivity is above the national average, however our ability to distinguish benign from cancerous lesions has room for improvement. This may reflect surgeon grade and concerns over prolonged waiting times delaying treatment. We therefore recommend regular skin cancer teaching and encourage all grades to use loupes, dermatoscopes and adequate lighting in clinic and theatre to ensure adequate margins and adherence to national guidelines.

Safety profile of upadacitinib in patients at risk of cardiovascular disease: integrated post hoc analysis of the SELECT phase III rheumatoid arthritis clinical programme

ObjectiveIncreased risk of serious adverse events (AEs) was reported for tofacitinib relative to tumour necrosis factor inhibitor therapy in patients with rheumatoid arthritis (RA) aged ≥50 years enriched for cardiovascular...

Therapeutic Cancer Vaccines for Nonmelanoma Skin Cancer.

The development of immunotherapies for nonmelanoma skin cancer (NMSC) has lagged far behind that for melanoma in the past few decades, given that the majority of cases are surgically curable. Nevertheless, given the steady growth in the incidence rate of NMSC and attendant increase in patients with unresectable or advanced-stage tumors, the demand for systemic therapy is noticeably increasing. To date, the most widely used immunotherapeutic strategies, including immune checkpoint inhibitors and T-cell therapy, have obtained satisfactory results in some patients but not others. Even with an objective response in a fraction of patients, some accompanying adverse events may lead to intolerance and noncompliance. The expanding understanding of immune surveillance and tumor escape has provided us with novel perspectives in the field of immunotherapy. One emerging approach, the therapeutic cancer vaccine, encompasses the potential to newly "prime" T cells by activating antigen presentation in regional lymph nodes and the tumor microenvironment. Immune cells are therefore preconditioned and awakened to be ready to attack tumors. In NMSCs, multiple clinical trials of cancer vaccines are underway. The vaccine targets include tumor-associated antigens, tumor-specific antigens, oncolytic viruses, and toll-like receptors. Although clinical benefits have been shown in specific case reports and trials, various challenges remain to be resolved to guarantee applicability in the general patient population. Standing on the shoulders of pioneers expedites the pace of advances in therapeutic cancer vaccines, making them the rising star in the field of immunotherapy.

A Review on the Safety of Using JAK Inhibitors in Dermatology: Clinical and Laboratory Monitoring.

Janus kinase (JAK) inhibitors are disease-modifying agents with efficacy in treating a spectrum of burdensome dermatologic conditions. The US Food and Drug Administration (FDA) recently placed a black box warning on this class of medications due to safety concerns based on data from studies investigating tofacitinib in patients with rheumatoid arthritis. Here we provide an overview of the timeline of FDA approval of JAK inhibitors in dermatology. We also discuss the available safety profiles of approved oral JAK1 inhibitors, namely abrocitinib and upadacitinib, oral baricitinib, a JAK1/2 inhibitor, deucravacitinib, a Tyk2 inhibitor, and the topical JAK1/2 inhibitor ruxolitinib in dermatology patients. Additionally, we offer suggestions for initial screening and laboratory monitoring for patients receiving JAK inhibitors. We found that the rates of venous thromboembolism reported in trials ranged from no events to 0.1-0.5% in dermatology-specific phase 3 clinical trials compared with no events in the placebo. The rates of cardiovascular events ranged from no events to 0.4-1.2% compared with no events to 0.5-1.2% in the placebo. The rates of serious infections were 0.4-4.8% compared with no events to 0.5-1.3% in the placebo. The rates of nonmelanoma skin cancer (NMSC) ranged from no event to 0.6-0.9% compared with no events in the placebo. The rates of non-NMSC ranged from no event to 0.2-0.7% compared with no event to 0.6% in the placebo. Most patients who developed these adverse events had risk factors for the specific event. The most common adverse events of oral JAK inhibitors included upper respiratory infections, nasopharyngitis, nausea, headache, and acne. Dermatologists should consider patients' baseline risk factors for developing serious complications when prescribing oral JAK inhibitors.

Trends of non-melanoma skin cancer incidence in Hong Kong and projection up to 2030 based on changing demographics

Objective To assess the trends in non-melanoma skin cancer (NMSC) incidence in Hong Kong from 1990 to 2019 and the associations of age, calendar period, and birth cohort, to make projections to 2030, and to examine the drivers of NMSC incidence. Methods We assessed the age, calendar period, and birth cohort effects of NMSC incidence in Hong Kong between 1990 and 2019 using an age-period-cohort model. Using Bayesian age-period-cohort analysis with integrated nested Laplace approximations, we projected the incidence of NMSC in Hong Kong to 2030. Results From 1990 to 2019, the age-standardized incidence rate of NMSC increased from 6.7 per 100,000 population to 8.6 per 100,000 population in men and from 5.4 per 100,000 to 5.9 per 100,000 population in women, among the 19,568 patients in the study (9812 male patients [50.14%]). The annual net drift was 2.00% (95% confidence interval [CI]: 1.50–2.50%) for men and 1.53% (95% CI: 0.95–2.11%) for women. Local drifts increased for both sexes above the 35–39-year age group. The period and cohort risk of developing NMSC tended to rise but slowed gradually in the most recent period and post-1975 birth cohort. From 2019 to 2030, it is projected that the number of newly diagnosed NMSC cases in Hong Kong will increase from 564 to 829 in men and from 517 to 863 in women. Population aging, population growth, and epidemiologic changes contributed to the increase in incident NMSCs, with population aging being the most significant contributor. Conclusion The slowing of the period and cohort effects suggests that the rising incidence of NMSC is partly attributable to increased awareness and diagnosis. The increasing prevalence of NMSC among the elderly and an aging population will significantly impact the clinical workload associated with NMSC for the foreseeable future.

The Chemoprotective Role of Vitamin D in Skin Cancer: A Systematic Review.

Research in mice showed that vitamin D receptor deficiency was correlated with an increased rate of non-melanoma skin cancer. Therapeutic supplemental vitamin D has also been reported to reduce cell growth in both melanoma and non-melanoma skin cancer. This paper aims to describe the existing research studies that discuss the potential and role of vitamin D in the management of skin cancer. Articles were searched from three databases (PubMed, ScienceDirect, Scopus) and manual search. 18 articles were included. These were further divided into in vivo and in vitro studies. The literature search was based on the following Patients, Intervention, Control, and Outcome (PICO) criteria: Patients with any types of skin cancer; Vitamin D and their derivates as the intervention; placebo or standard regimen as control, and survival rate or response rate as primary outcome. From the three databases, we obtained 802 studies. Prior to screening of the literature obtained, several studies were excluded. In the eligibility assessment, seven studies were excluded due to their outcomes being not eligible for analysis, and two studies were excluded due to inaccessible full texts. The remaining 18 studies were included. Five studies had a clinical research design (randomized controlled trial or interventional study), which use vitamin D3 as vitamin D derivatives and the results showed that the administration of vitamin D3 reduces the proliferation of skin cancer cells. Similar results were also reported in studies with pre-clinical research designs, either in vivo or in vitro, where six were in vivo studies and nine studies were in vitro studies. Our literature review revealed that that vitamin D derivatives, such as 1,25(OH)2D3 or 20(OH)D3 can effectively reduce the proliferation of skin cancer cells by contributing in the inhibition of cell growth and development, highlighting vitamin D's role as good prognostic factor.

JAK Inhibitor Safety Compared to Traditional Systemic Immunosuppressive Therapies.

Dermatologists treating atopic dermatitis are interested in the safety profile of the recently available JAK inhibitors, upadacitinib and abrocitinib, especially after they received boxed safety warnings. Long-term clinical trial data using these JAK inhibitors for the treatment of atopic dermatitis suggest that they are associated with very low incidence rates of malignancy, major adverse cardiac events, and thromboembolic events. However, a knowledge gap exists regarding the incidence of adverse events for JAK inhibitors compared to traditional systemic therapies used to treat poorly controlled atopic dermatitis as well as baseline rates in both atopic dermatitis and reference control populations. To address this gap, we analyzed data regarding adverse events of special interest for methotrexate, cyclosporine, and systemic corticosteroids and calculated the incidence of adverse events per 100 patient-years for these drugs. We also examined data regarding baseline incidence of adverse events in atopic dermatitis and control patients. We found that compared to upadacitinib and abrocitinib, traditional systemic therapies for atopic dermatitis demonstrated equal or higher incidence rates for malignancy (excluding non-melanoma skin cancer), non-melanoma skin cancer, major adverse cardiac events, and venous thromboembolism. Moreover, the use of upadacitinib and abrocitinib also exhibited either comparable or lower incidence of malignancy (excluding non-melanoma skin cancer), major adverse cardiac events, and venous thromboembolism, but higher rates of non-melanoma skin cancer, in comparison to baseline rates in atopic dermatitis or control patients. These findings indicate that JAK inhibitors should be positioned, at least based on safety, ahead of traditional systemic therapies for atopic dermatitis treatment.J Drugs Dermatol. 2022;21(12):1298-1303. doi:10.36849/JDD.7187.

Sun protective behaviors in sun-sensitive individuals: a cross-sectional study examining for ethnic and racial differences.

The rates of non-melanoma skin cancer continue to rise in the United States. We investigated if differences exist in skin cancer preventive behaviors among sun-sensitive non-Hispanic whites and other racial and ethnic groups. The National Health Information Survey was used to perform the cross-sectional study. Outcomes of interest included multiple sun-protective methods. Individuals were determined to be sun-sensitive if Fitzpatrick skin phototype (SPT) I/II. Multivariable logistic regression was used to examine the associations between the use of sun-protective practices and race and ethnicity, SPT, and survey year. The study included 67,471 individuals. Adjusted prevalences of skin cancer preventive behaviors revealed that across all SPTs, non-Hispanic whites were more likely to use sunscreen, undergo physician-administered FBSE, and have multiple sunburns or tan indoors in the past year compared to corresponding SPT other racial and ethnic groups. In contrast, other racial and ethnic groups with any SPT were more likely to practice sun avoidance than corresponding SPT non-Hispanic whites. Additionally, other racial and ethnic groups with SPT III+ were more likely to wear sun-protective clothing than non-Hispanic white individuals with similar SPTs. For all SPT and racial and ethnic groups, there were significant increases in sunscreen use and decreases in past-year indoor tanning. Full body skin examination prevalence, regardless of sun sensitivity, increased for all non-Hispanic whites, but remained unchanged for sun-sensitive other racial and ethnic groups. Adjusted prevalence of multiple sunburns and use of protective clothing remained unchanged for all racial and ethnic groups across all SPT categories. There are differences in sun-protective behaviors among sun-sensitive individuals by race and ethnicity with the magnitude of some of these differences increasing. Future research and public health campaigns are needed on photosensitive individuals and the relationship between skin protective behaviors and race/ethnicity. When discussing sun protection, care providers should not only consider the influence of sun-sensitivity, but also race and ethnicity, and its impact on sun prevention behaviors.

Efficacy and Safety of Upadacitinib in Patients with Psoriatic Arthritis: 2-Year Results from the Phase 3 SELECT-PsA 1 Study.

IntroductionEfficacy and safety of the Janus kinase (JAK) inhibitor upadacitinib (UPA) was evaluated in patients with psoriatic arthritis (PsA) through week 104 of the ongoing long-term extension of the phase 3 trial SELECT-PsA 1.MethodsExploratory analyses of all primary and secondary endpoints (non-responder imputation and as observed for binary endpoints; mixed-effect model repeated measures and as observed for continuous endpoints), and summary of treatment-emergent adverse events, in patients receiving UPA 15 mg (UPA15) or 30 mg (UPA30) once daily, or adalimumab 40 mg (ADA) every other week, through week 104 are reported.ResultsOf 1704 patients, 25.4% discontinued the study drug by week 104. Proportions of patients achieving ≥ 20%/50%/70% improvement in American College of Rheumatology criteria (ACR20/50/70), ≥ 75%/90%/100% improvement in Psoriasis Area and Severity Index (PASI75/90/100), or minimal disease activity (MDA) were maintained through week 104; greater responses by nominal P value were observed with UPA15 and UPA30 versus ADA for ACR20/50/70 and MDA. Mean change from baseline in modified total Sharp/van der Heijde Score (mTSS) was similar across groups and to week 56 results. The safety profile of UPA was generally comparable to ADA and not altered from week 56 data. Rates of serious infection, herpes zoster, anemia, neutropenia, lymphopenia, and elevated creatine phosphokinase remained numerically higher with UPA15 and/or UPA30 versus ADA. Rates of malignancies excluding non-melanoma skin cancer (NMSC), major adverse cardiovascular events, and venous thromboembolism were similar across groups; rates of NMSC were higher with UPA versus ADA. Two deaths were reported with UPA15, one with UPA30, and one with ADA.ConclusionsIn PsA patients, efficacy responses were similar or greater with UPA15 or UPA30 versus ADA through week 104, and inhibition of radiographic progression was maintained. No new safety risks were identified with exposure to UPA through 2 years (week 104).Clinical Trial RegistrationClinicalTrials.gov, NCT03104400.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40744-022-00499-w.

34914 Long-term safety of risankizumab in patients with psoriatic disease: Findings from integrated analyses of 17 clinical trials in psoriasis and 4 in psoriatic arthritis

Objective: To report long-term risankizumab safety in patients with psoriatic disease. Method: Risankizumab safety data to March 25, 2021 were pooled from 17 phase 1–3 clinical trials in plaque psoriasis (PsO) and 4 phase 2/3 trials in psoriatic arthritis (PsA). Adverse events (AEs) of safety interest were reported for patients receiving ≥1 dose risankizumab. Results: Among 3197 patients with PsO (9982.6 patient years’ [PY] exposure; median (range) treatment duration, 3.7 years [1 day–6.9 years]) and 1542 patients with PsA (1594.9 PY; 1.0 year [84 days–2.0 years]), rates of treatment-emergent AEs (158.3 and 160.8 events (E)/100PY), serious AEs (7.6 and 8.4 E/100PY) and AEs leading to discontinuation (1.9 and 2.3 E/100PY) were similar. Nasopharyngitis (PsO 14.5 E/100PY , PsA 7.9 E/100PY) and upper respiratory infection (PsO 7.8 E/100PY, PsA 5.6 E/100PY) were the most common infections; sepsis and pneumonia for PsO (0.1 E/100PY each) and COVID-19 for PsA (0.4 E/100PY) were the most common serious infections. Rates of opportunistic fungal infections were <0.1 and 0.1 E/100PY in PsO/PsA patients. Rates of nonmelanoma skin cancer (NMSC) were 0.7 and 0.4 E/100PY, and malignant tumors excluding NMSC were 0.6 and 0.3 E/100PY in PsO/PsA patients. Rates of major adverse cardiovascular events were 0.5 and 0.4 E/100PY in PsO/PsA patients. Conclusion: Rates of AEs of safety interest remained low in this largest and longest safety reporting for risankizumab to date, supporting the safety of risankizumab for the long-term treatment of patients with psoriatic disease.

Changing trends in the disease burden of non-melanoma skin cancer globally from 1990 to 2019 and its predicted level in 25 years

BackgroundThe disease burden of non-melanoma skin cancer (NMSC) has become a significant public health threat. We aimed to conduct a comprehensive analysis to mitigate the health hazards of NMSC.MethodsThis study had three objectives. First, we reported the NMSC-related disease burden globally and for different subgroups (sex, socio-demographic index (SDI), etiology, and countries) in 2019. Second, we examined the temporal trend of the disease burden from 1990 to 2019. Finally, we used the Bayesian age-period-cohort (BAPC) model integrated nested Laplacian approximation to predict the disease burden in the coming 25 years. The Norpred age-period-cohort (APC) model and the Autoregressive Integrated Moving Average (ARIMA) model were used for sensitivity analysis.ResultsThe disease burden was significantly higher in males than in females in 2019. The results showed significant differences in disease burden in different SDI regions. The better the socio-economic development, the heavier the disease burden of NMSC. The number of new cases and the ASIR of basal cell carcinoma (BCC) were higher than that of squamous cell carcinoma (SCC) in 2019 globally. However, the number of DALYs and the age-standardized DALYs rate were the opposite. There were statistically significant differences among different countries. The age-standardized incidence rate (ASIR) of NMSC increased from 54.08/100,000 (95% uncertainty interval (UI): 46.97, 62.08) in 1990 to 79.10/100,000 (95% UI: 72.29, 86.63) in 2019, with an estimated annual percentage change (EAPC) of 1.78. Other indicators (the number of new cases, the number of deaths, the number of disability-adjusted life years (DALYs), the age-standardized mortality rate (ASMR), and the age-standardized DALYs rate) showed the same trend. Our predictions suggested that the number of new cases, deaths, and DALYs attributable to NMSC would increase by at least 1.5 times from 2020 to 2044.ConclusionsThe disease burden attributable to NMSC will continue to increase or remain stable at high levels. Therefore, relevant policies should be developed to manage NMSC, and measures should be taken to target risk factors and high-risk groups.