Incidence Of Non-melanoma Skin Cancer Research Articles

42756 Incidence of Non-melanoma and Melanoma Skin Cancer in Sexual Minority Groups: A Retrospective Comparative Cohort Study

42756 Incidence of Non-melanoma and Melanoma Skin Cancer in Sexual Minority Groups: A Retrospective Comparative Cohort Study

Patients’ willingness to accept adverse event and cost tradeoffs from oral nicotinamide for reduced risk of non-melanoma skin cancer

BackgroundNon-immunosuppressed patients with a history of multiple non-melanoma skin cancers (NMSCs) taking oral nicotinamide supplementation experienced a 23% decrease in annual NMSC risk in a randomized clinical trial. Patient preferences for risks and costs associated with nicotinamide are unknown.ObjectivesTo understand how patients prioritize NMSC reduction, infection risk, and cost.MethodsA sample of adults with history of ≥2 NMSC within the past five years undergoing Mohs procedure completed a discrete-choice experiment comprising two hypothetical treatments—characterized by varying reductions in NMSC incidence, increased severe infection risk, and cost—and no treatment. The data were analyzed with random-parameters logit models.ResultsA total of 203 subjects (mean age 71.5 years, 65.5% males) participated. For a 23% annual reduction in NMSC incidence, a 26% [95% CI: 8%–45%] annual increase in severe infection risk and $8 [95% CI: $2–14] monthly cost was acceptable. Outcomes across analyzed subgroups (before vs. during COVID pandemic, site of interview, less vs. more prior NMSCs) were similar.ConclusionsPatients were unwilling to accept high severe infection risks to obtain the reduction in NMSC incidence observed in a nicotinamide trial, suggesting that routinely recommending nicotinamide may run counter to some patients’ preferences.

Importance of accounting for timing of time-varying exposures in association studies: Hydrochlorothiazide and non-melanoma skin cancer.

Hydrochlorothiazide (HCTZ), a widely prescribed antihypertensive drug with photosensitising properties, has been linked with non-melanoma skin cancer (NMSC) risk. However, previous analyses did not fully explore if and how the impact of past HCTZ exposures accumulates with prolonged use and/or depends on time elapsed since exposures. Therefore, we used different models to more comprehensively assess how NMSC risk vary with HCTZ exposure, and explore how the results may depend on modeling strategies. We used different parametric models with alternative time-varying exposure metrics, and the flexible weighted cumulative exposure model (WCE) to estimate associations between HCTZ exposures and NMSC risk in a population-based cohort of HCTZ users over 65 years old, in the province of Ontario, Canada. Among 3844 HCTZ users, 273 developed NMSC during up to 8 years of follow-up. In parametric models, based on all exposures, increased duration of past HCTZ use was associated with an increase of NMSC risk but cumulative dose showed no systematic association. Yet, WCE results suggested that only exposures taken 2.5-4 years in the past were associated with the current NMSC hazard. This finding led us to re-define the parametric models, which also confirmed that any HCTZ dose taken outside this time-window were not systematically associated with NMSC incidence. Our analyses illustrate how flexible modeling may yield new insights into complex temporal relationships between a time-varying drug exposure and risks of adverse events. Duration and recency of antihypertensive agents exposures must be taken into account in evaluating risk and benefits.

Maintenance lenalidomide in newly diagnosed transplant eligible and non-eligible myeloma patients; profiling second primary malignancies in 4358 patients treated in the Myeloma XI Trial

Early trials of long-term lenalidomide use reported an increased incidence of second primary malignancy (SPM), including acute myeloid leukaemia and myelodysplastic syndrome. Later, meta-analysis suggested the link to be secondary to lenalidomide in combination with melphalan. Myeloma XI is a large, phase III randomised trial in-which lenalidomide was used at induction and maintenance, in transplant eligible (TE) and non-eligible (TNE) newly diagnosed patients (NCT01554852). Here we present an analysis of SPM incidence and profile the SPM type to determine the impact of autologous stem cell transplantation (ASCT) and lenalidomide exposure in 4358 patients treated on study. Data collection took place from the start of the trial in May 2010, to May 2019, as per the protocol timeline. The Median follow-up following maintenance randomisation was 54.5 and 46.1 months for TE and TNE patients, respectively. In the TE pathway, the overall SPM incidence was 7.7% in lenalidomide maintenance patients compared to 3.2% in those being observed (p=0.006). Although the TNE lenalidomide maintenance patients had the greatest SPM incidence (15.4%), this was not statistically significant when compared to the observed patients (10%, p=0.10).The SPM incidence was higher in patients who received lenalidomide at induction and maintenance (double exposure), when compared to those treated with lenalidomide at one time point (single exposure). Again, this was most marked in TNE patients where the overall SPM incidence was 16.9% in double exposed patients, compared to 11.7% in single exposed patients, and 11.2% in patients who did not receive lenalidomide (p=0.04). This is likely an effect of treatment duration, with the median number of cycles being 27 in the TNE double exposed patients, vs 6 in the single exposure patients.Haematological SPMs were uncommon, diagnosed in 50 patients (incidence 1.1%). The majority of cases were diagnosed in TE patients treated with lenalidomide maintenance (n=25, incidence 2.8%), suggesting a possible link with melphalan. Non-melanoma skin cancer incidence was highest in patients receiving lenalidomide maintenance, particularly in TNE patients, where squamous cell carcinoma and basal cell carcinoma were diagnosed in 5.5% and 2.6% of patients, respectively. The incidence of most solid tumour types was higher in lenalidomide maintenance patients.Mortality due to progressive myeloma was reduced in patients receiving lenalidomide maintenance, noted to be 16.6% compared 22.6% in those observed in TE patients and 32.7% compared to 41.5% in TNE patients. SPM related mortality was low, 1.8% and 6.1% in TE and TNE lenalidomide maintenance patients, respectively, compared to 0.4% and 2.8% in those being observed. This provides reassurance that long-term lenalidomide treatment is safe and associated with improved outcomes in TE and TNE populations, although monitoring for SPM development should be incorporated into clinic review processes. Primary financial support was from Cancer Research UK [C1298/A10410].

Skin cancer risk of menopausal hormone therapy in a Korean cohort

Conflicting studies exist on the association between menopausal hormone therapy (MHT) and skin cancers, such as melanoma and non-melanoma skin cancer (NMSC). This retrospective cohort study aimed to evaluate the risk of skin cancer from MHT using data from 2002 to 2019 from the National Health Insurance Service in South Korea. We included 192,202 patients with MHT and 494,343 healthy controls. Women > 40 years who had menopause between 2002 and 2011 were included. Patients with MHT had at least one MHT for at least 6 months and healthy controls had never been prescribed MHT agents. We measured the incidence of melanoma and NMSC. Melanoma developed in 70 (0.03%) patients with MHT and 249 (0.05%) controls, while the incidence of NMSC was 417 (0.22%) in the MHT group and 1680 (0.34%) in the controls. Tibolone (hazard ratio [HR] 0.812, 95% confidence interval [CI] 0.694–0.949) and combined oestrogen plus progestin by the manufacturer (COPM; HR 0.777, 95% CI 0.63–0.962) lowered the risk of NMSC, while other hormone groups did not change the risk. Overall, MHT was not associated with melanoma incidence in menopausal Korean women. Instead, tibolone and COPM were associated with a decrease in NMSC occurrence.

Management of Cutaneous Head and Neck Squamous and Basal Cell Carcinomas for Immunocompromised Patients.

The incidence of non-melanoma skin cancer (NMSC) continues to rise, and more than one million cases are diagnosed in the United States each year. The increase in prevalence has been attributed to increased lifespan and improvements in survival for conditions that increase the risk of these malignancies. Patients who are immunocompromised have a higher risk of developing NMSC compared to the general population. In immunosuppressed patients, a combination of prevention, frequent surveillance, and early intervention are necessary to reduce morbidity and mortality. In this review, we collate and summarize current knowledge regarding pathogenesis of head and neck cutaneous SCC and BCC within immunocompromised patients, examine the potential role of the immune response in disease progression, and detail the role of novel immunotherapies in this subset of patients.

007 Vitiligo is associated with a reduction in incidence of melanoma and nonmelanoma skin cancer: UK population-based cohort study

Abstract Vitiligo is a common, acquired depigmenting skin disease. There have been concerns that vitiligo and its treatment may increase the risks of skin cancer. In a large UK population-based study, we aimed to establish whether vitiligo is associated with an increased risk of skin cancer. We used routinely collected electronic medical records of adults contributing to the Optimum Patient Care Research Database (2010–2020). Cases of vitiligo were identified using specific diagnosis codes. Those with other depigmenting conditions were excluded. Vitiligo cases were age and sex matched with up to four controls registered at the same general practice and with at least one primary care interaction in the preceding year. The primary outcome was risk of skin cancer; comprisied of melanoma, squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). Individual skin cancers and actinic keratoses (AK) were included as secondary outcomes. Associations between vitiligo and skin cancer were estimated using Cox regression, with adjustment for age, sex, socioeconomic deprivation, ethnicity, body mass index, smoking and alcohol status, immunotherapy, phototherapy and 13 common comorbidities. Prespecified subgroup analysis comprised stratification by sex, age group (18–45 years, 45–65 years and > 65 years), ethnicity (White and non-White) and socioeconomic deprivation. In total, 14 976 patients with vitiligo were matched to 54 392 controls. Over the 10-year study period, 133 patients with vitiligo and 783 controls developed new-onset skin cancer. Vitiligo was associated with a 38% reduced risk of any new-onset skin cancer [adjusted hazard ratio (aHR) 0.62, 95% confidence interval (CI) 0.51–0.74; P < 0.001]. This risk reduction was observed for all individual skin cancer types: melanoma (aHR 0.38, 95% CI 0.23–0.64; P < 0.001), SCC (aHR 0.65, 95% CI 0.48–0.87; P = 0.004), BCC (aHR 0.65, 95% CI 0.51–0.83; P < 0.001) and AK (aHR 0.86, 95% CI 0.75–0.98; P = 0.028). In a subgroup analysis, vitiligo was associated with a reduction in skin cancer risk in people identifying as White (aHR 0.68, 95% CI 0.55–0.84; P < 0.001), but there was no association in those identifying as non-White (aHR 0.93, 95% CI 0.44–1.98). Vitiligo-associated reductions in skin cancer risk were consistently observed in the other prespecified subgroups. Vitiligo is associated with a strong protective effect against common types of skin cancer. Vitiligo-associated risk reduction is most marked for melanoma (62% lower risk). Protective effects associated with vitiligo may be restricted to people with light skin, although skin cancers in the those with darker skin were uncommon, which requires further study. FundingThis research was sponsored by Pfizer. Medical writing and statistical support was provided by Momentum Data and was funded by Pfizer.

BI31 Hereditary haemochromatosis: a risk factor for nonmelanoma skin cancer?

Abstract Hereditary haemochromatosis (HH) is an autosomal recessive disease resulting in excessive levels of iron. In a recent study, in a US population of 448 patients diagnosed with HH, a positive association between HH and nonmelanoma skin cancers (NMSCs) was observed (Pan CX, Yang K, Lau CB et al. Non-melanoma skin cancer in patients with hereditary hemochromatosis: a case–control study. J Am Acad Dermatol 2023; 88:692–4). The authors also reported that, among those who required more frequent venesection, the risk of basal cell carcinoma (BCC) was particularly elevated. In terms of the possible pathomechanism, the authors noted that oxidative stress represents a key component in the pathogenesis of both HH and BCC. Ireland has the highest prevalence of HH in the world, with research suggesting approximately 1 in 83 people is predisposed. For this reason, a study was undertaken to determine if a similar association could be observed in an Irish population. A single-centre retrospective cross-sectional analysis was undertaken on a database of patients with haemochromatosis attending the venesection department of a tertiary referral centre over 25 years (1997–2022). All histologically diagnosed NMSCs within this patient group were then recorded. Ethical approval was granted by the local hospital ethics committee. There were a total 1480 patients in the database, 65% Male (n = 956). Five were excluded due to insufficient data. Thus, 1475 patients were analysed, 64% male (n = 949). The mean current age was 60 years (range: 19–100). Only 52/1475 patients (3.5%) had a histologically diagnosed NMSC, 52% male (n = 27). HH genetic mutation: C282Y homozygous (n = 29); H63D homozygous (n = 5); C282Y/H63D compound heterozygous (n = 11); and data not recorded (n = 7). Mean ferritin at HH diagnosis 575 (range: 0–8413). Forty-three patients were diagnosed with a BCC, 58% male (n = 25), with a total of 94 BCCs. Mean age was 67 years at first NMSC diagnosis. Histological classification: nodular (n = 48); superficial (n = 19); unclassified (n = 18); infiltrative (n = 5); micronodular (n = 3); and basosquamous (n = 1). Eleven patients were diagnosed with a squamous cell carcinoma (SCC), with a total of 21 SCCs. This study had limitations. It was a single-centre, retrospective study analysing only histologically confirmed NMSCs. It is acknowledged that a small proportion of NMSCs may be diagnosed clinically, specifically superficial BCCs without histological confirmation. Only records with histology available in our institution were recorded, and it is possible that NMSCs were excised in other institutions, potentially leading to an under-representation of NMSC incidence. The proportion of patients diagnosed with NMSCs in this cohort was relatively low, in contrast to the findings reported by Pan et al. This study indicates that HH is unlikely to represent an independent risk factor.

1386-P: Dipeptidyl Peptidase-4 Inhibitors and the Risk of Skin Cancer among Patients with Type 2 Diabetes—Population-Based Cohort Study

Introduction: The dipeptidyl peptidase-4 (DPP-4) enzyme influences carcinogenic pathways in the skin, although its exact role remains uncertain. The objective of this study was to determine whether DPP-4 inhibitors are associated with the incidence of melanoma and nonmelanoma skin cancer, compared with sulfonylureas. Research Design and Methods: Using the United Kingdom Clinical Practice Research Datalink, we assembled two new-user active comparator cohorts for each skin cancer outcome from 2007 to 2019. For melanoma, the cohort included 96,739 DPP-4 inhibitor users and 209,341 sulfonylurea users, and 96,411 DPP-4 inhibitor users and 208,626 sulfonylurea users for nonmelanoma skin cancer. Propensity score fine stratification weighted Cox proportional hazards models were to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) of melanoma and nonmelanoma skin cancer, separately. Results: Overall, DPP-4 inhibitors were associated with a 23% decreased risk of melanoma compared with sulfonylureas (49.7 vs. 65.3 per 100,000 person-years, respectively; HR 0.77, 95% CI 0.61-0.96). The HR progressively reduced with increasing cumulative duration of use (0-2 years HR 1.14, 95% CI 0.84-1.54; 2.1-5 years HR 0.44, 95% CI 0.29-0.66; >5 years HR 0.33, 95% CI 0.14-0.74). In contrast, these drugs were not associated with the incidence of nonmelanoma skin cancer, compared with sulfonylureas (448.1 vs. 426.1 per 100,000 person-years, respectively; HR 1.06, 95% CI 0.98-1.15). Conclusions: In this large, population-based cohort study, DPP-4 inhibitors were associated with a reduced risk of melanoma but not nonmelanoma skin cancer, compared with sulfonylureas. Disclosure R.Pradhan: None. L.Azoulay: Advisory Panel; Pfizer Inc., Consultant; Pfizer Inc., Speaker's Bureau; Roche Diagnostics. R.W.Platt: Advisory Panel; Pfizer Inc., Consultant; Boehringer Ingelheim (Canada) Ltd., Biogen, Merck & Co., Inc., Nant Pharma, Other Relationship; Boehringer Ingelheim Inc. O.Yu: Consultant; Novo Nordisk. Funding Canadian Institutes of Health Research (FDN143328)

Correlation of Ultraviolet Radiation Levels With the Incidence of Cutaneous Squamous Cell and Merkel Cell Carcinomas in Non-sunbelt Locales in the United States: 2010-2017.

Non-melanoma skin cancer (NMSC) is the most common human malignancy worldwide, with increasing incidence in the United States (US). Recent environmental data have shown that ultraviolet radiation (UVR) levels have increased in the US, particularly in the higher latitudes, but the potential impact of this on NMSC incidence is not well known, despite estimates that 90% of NMSC is due to sun exposure. Our exploratory study synthesizes environmental data with demographic and clinical data to determine whether UV indices (UVIs) and non-sunbelt (non-SB) locale (latitudes >40 degrees, which comprises most of the US) might contribute to incidence rates of two types of NMSC: cutaneous squamous cell and Merkel cell carcinomas. UVIs from 2010 to 2017 were obtained from the National Oceanic and Atmospheric Administration database and meshed with corresponding locales in the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database (version 8.4.0.1). Four SB and five NSB locales contained sufficient data for analysis. Linear mixed modeling was performed with the outcome variable of the age-adjusted incidence of NMSC cancer (comprised of cutaneous squamous cell carcinoma of the head and neck (CSCCHN) and Merkel cell carcinoma (MCC)), the two most common types of NMSC contained within SEER). Non-SB locale and percent of days with UVI >3 were independent variables. Percent of days with UVI >3 increased during this period, as did the overall NMSC (combined CSCCHN and MCC) skin cancer incidence, though MCC incidence alone did not increase during our study period.Environmental factors that significantly contributed to the age-adjusted overall NMSC (combined CSCCHN and MCC) cancer incidence (per 100,000 individuals) included NSB locale (b=1.227, p=0.0019) and percent of days with UVIs >3 (b=0.028, p<0.0001), as well as clinical factors of percent white race and percent male, by linear mixed modeling. Our results are limited by the completeness of the NOAA and SEER databases, and do not include basal cell carcinoma. Nevertheless, our data demonstrate that environmental factors, such as latitude in NSB locale and UVI indices, can affect the age-adjusted overall NMSC (defined as CSCCHN and MCC in this study) incidence even in this relatively short period of time. Prospective studies over longer time periods are needed to identify the extent to which these findings are clinically significant so that increased educational efforts to promote sun-safe behaviors can be maximally effective.

Incidence of skin cancer among patients with Waldenström macroglobulinemia: Analysis of the SEER database (2000-2019).

e18893 Background: The association between non-Hodgkin lymphoma, including chronic lymphocytic leukemia, and aggressive skin cancers is well established. We studied the incidence of melanoma and non-melanoma skin cancers (NM) skin malignancies (SM) among patients with Waldenstrom macroglobulinemia (WM). Methods: We used the SEER 17 registry to identify adult [Age &gt; 20] patients(pts) with an index diagnosis (dx) of WM between 2000- 2019. We included ICD-O-3 codes 9671/3 (Lymphoplasmacytic lymphoma) and 9761/ (Waldenstrom macroglobulinemia) to identify index dx. Only first of the two codes was used if both were mentioned for same pt. We excluded patients with diagnosis made from death certificate or autopsy. We used ICD-O-3/WHO 2008 codes assigned to melanoma of skin and other NM SM to identify subsequent diagnosis ( &gt; 2months after index diagnosis) of SM excluding basal cell and squamous cell cancers. SM were categorized using ICD-O-3 codes for histology. Follow up period was till December 2019. Data variables and standardized incidence ratio [SIR] for SM were obtained with multiple primary SIR analyses using SEER Stat v 8.4.0.1 software. Kaplan Meier method was used to estimate overall survival (OS) using R 4.2.2. Results: We identified 8099 patients with WM of which 68 patients (0.84%) had a subsequent dx of SM. WM and SM were diagnosed at median (IQR) ages of 69 (60-77) and 74 (67-81), with a median gap of 52 (30-95) months. Majority of WM survivors with SM were males (51 or 75%), white (100%) and older than 60 years of age (72%) at WM diagnosis. Almost half of the patients who developed SM underwent chemotherapy for WM (n = 35, 45%). The overall risk of developing SM was significantly higher in WM patients as compared to the general population [SIR (95%CI) = 1.34 (1.01-1.74) (p &lt; 0.05) for melanoma and 2.85 (1.52-4.87) (p &lt; 0.05) for NM]. Eleven different types of histology for SM were noted, with malignant melanoma, NOS (n = 30, 44%) and Merkel cell carcinoma (n = 7, 10%) being the most common melanoma and NM subtype (Table). The median survival after SM dx was 68 (55-NA) months. Conclusions: Patient with WM had higher risk of SM (melanoma and NM skin cancers, excluding basal cell and squamous cell cancers) compared to the general population. This study highlights the need for screening and counseling for skin cancers in WM patients in routine clinical practice. [Table: see text]

Competing risk nomogram for predicting cancer-specific mortality in patients with non-melanoma skin cancer.

This study aimed to assess the cumulative incidences of Non-melanoma skin cancer (NMSC)-specific mortality (NMSC-SM) and develop a competing risk nomogram for NMSC-SM. Data on patients diagnosed with NMSC between 2010 and 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. To identify the independent prognostic factors, univariate and multivariate competing risk models were used, and a competing risk model was constructed. Based on the model, we developed a competing risk nomogram to predict the 1-, 3-, 5-, and 8-year cumulative probabilities of NMSC-SM. The precision and ability to discriminate of the nomogram were evaluated through the utilization of metrics, such as receiver-operating characteristic (ROC) area under the curve (AUC), concordance index (C-index), and a calibration curve. Decision curve analysis (DCA) was employed to assess the clinical usefulness of the nomogram. Race, age, the primary site of the tumor, tumor grade, size, histological type, summary stage, stage group, order of radiation and surgery, and bone metastases were identified as independent risk factors. The prediction nomogram was constructed using the variables mentioned above. The ROC curves implied the good discrimination ability of the predictive model. The nomogram's C-index was 0.840 and 0.843 in the training and validation sets, respectively, and the calibration plots were well fitted. In addition, the competing risk nomogram demonstrated good clinical usefulness. The competing risk nomogram displayed excellent discrimination and calibration for predicting NMSC-SM, which can be used in clinical contexts to help guide treatment decisions.

Risk of Melanoma and Nonmelanoma Skin Cancer in People with Vitiligo: United Kingdom Population−Based Cohort Study

Although genetic studies have found an inverse relationship between vitiligo and skin cancer, epidemiological evidence is conflicting. We investigated the risk of skin cancer in adults with vitiligo using United Kingdom electronic primary care records from the Optimum Patient Care Research Database 2010-2020. Vitiligo cases were age, sex, and general practitioner practice matched to population controls without vitiligo. Incidence of melanoma, nonmelanoma skin cancers (squamous cell carcinoma and basal cell carcinoma), and actinic keratoses was compared between vitiligo cases and controls using Cox regression. A total of 15,156 vitiligo cases were matched to 60,615 controls. Vitiligo was associated with a 38% reduced risk of new-onset skin cancer (adjusted hazard ratio [aHR]= 0.62, 95% confidence interval [CI]= 0.52-0.75, P < 0.001) and skin cancer subtypes; melanoma (aHR= 0.39, 95% CI= 0.23-0.65, P < 0.001), squamous cell carcinoma (aHR= 0.67, 95% CI= 0.49-0.90, P < 0.01), basal cell carcinoma (aHR= 0.65, 95% CI= 0.51-0.83, P < 0.001). There was no significant association for actinic keratosis (aHR= 0.88, 95% CI= 0.77-1.01). People with vitiligo have a markedly reduced incidence of melanoma and nonmelanoma skin cancer. Given concerns that some treatments, such as phototherapy, may increase skin cancer risk, this finding provides reassurance to people with vitiligo and clinicians managing the condition.

OA06 Clinical outcomes of filgotinib in patients with rheumatoid arthritis aged ≥65 years: a post hoc subgroup analysis of Phase 2 and 3 clinical trials and ongoing long-term extensions

Abstract Background/Aims Filgotinib (FIL) is a Janus kinase 1 preferential inhibitor approved for treatment of moderate-severe active RA. A numerically higher proportion of patients (pts) ≥65y vs &amp;lt; 65y had an adverse event (AE), serious AE, or serious infection (SI) in the FIL 200 mg (FIL200) group of the pooled phase 2 and 3 safety studies. We report updated data on AEs of special interest (AESIs) and efficacy in these age groups. Methods This post hoc analysis assessed safety and efficacy in pts aged &amp;lt;65y and ≥65y using data from phase 2 DARWIN 1 (NCT01888874) and 2 (NCT01894516); phase 3 FINCH 1 (NCT02889796), 2 (NCT02873936), and 3 (NCT02886728); and DARWIN 3 (NCT02065700) and FINCH 4 (NCT03025308) long-term extension (LTE) trials. All pts with RA fulfilled 2010 ACR/EULAR criteria. Data as of Jan 11, 2022 (DARWIN 3) and Jan 31, 2022 (FINCH 4). Analyses performed on an ad hoc interim analysis data set without additional cleaning. The as-treated analysis set included all available data for pts receiving ≥1 FIL dose (FIL200/FIL 100 mg [FIL100]), including those rerandomized to FIL in the LTE. Censored exposure-adjusted incidence rates (EAIRs)/100 patient-years of exposure of AESIs by age category (&amp;lt;65y vs ≥ 65y) are presented. EAIR and 95% confidence intervals (CIs) were calculated. Proportions of pts aged &amp;lt;65y and ≥65y achieving a 20, 50 and 70% improvement in ACR criteria (ACR20/50/70) and DAS28-CRP low disease activity (LDA) at Week 144 in FINCH 4, estimated using observed cases, are reported. Results Patients ≥65y had higher proportions of cardiovascular (CV) risk factors at baseline vs those &amp;lt;65y. EAIRs of AESIs were generally higher in pts aged ≥65y than &amp;lt;65y. In pts aged ≥65y, the EAIRs of adjudicated major adverse cardiovascular events, venous thromboembolisms, SI, and herpes zoster differed between the 2 FIL doses with partly or largely overlapping CIs. The EAIRs of nonmelanoma skin cancer (NMSC), malignancies (excluding NMSC), and treatment-emergent AE (TEAE) leading to death were numerically higher in the ≥65y age group only, with FIL200 vs FIL100. The most reported fatal outcomes with FIL200 in the ≥65y age group were malignancies, cardiac disorders, and infections and infestations. ACR20/50/70 and DAS28-CRP LDA rates in pts aged &amp;lt;65 and ≥65y in FINCH 4 were maintained or numerically higher with FIL200 to Week 144. Conclusion In this post hoc integrated safety analysis, the EAIRs of AESIs were generally higher in pts aged ≥65y than &amp;lt;65y. A numerically higher incidence of NMSC, malignancies (excluding NMSC), and TEAEs leading to death was observed in the FIL200 vs FIL100 group in pts aged ≥65y only. In FINCH 4, efficacy was maintained in both age groups. Limitations include the ad hoc nature of analysis, overlapping CIs, lack of comparator data, and potential LTE bias. Disclosure M.H. Buch: Other; AbbVie, Galapagos, Gilead, Pfizer, Eli Lilly, Merck-Serono, Roche, UCB. B. Combe: Other; AbbVie, Bristol Myers Squibb, Celltrion, Galapagos, Gilead, Janssen, Lilly, MSD, Pfizer, Roche-Chugai, Novartis. J.A. Gómez-Puerta: Other; GSK, Galapagos, Pfizer, Janssen, Sanofi, AbbVie, Bristol Myers Squibb, Lilly, Novartis, MSD, Roche. R. Caporali: Other; AbbVie, Celltrion, Fresenius-Kabi, Galapagos, Janssen, Pfizer, Roche, UCB, Eli Lilly, Gilead, Sanofi. J. Gottenberg: Other; AbbVie, Bristol Myers Squibb, Galapagos, Gilead, Lilly, MSD, Novartis, Pfizer. P. Van Hoek: Other; Galapagos. V. Rajendran: Other; Galapagos. P. Stiers: Other; Galapagos. K. Van Beneden: Other; Galapagos. D. Aletaha: Other; Novartis, SoBi, Sanofi, Amgen, Lilly, Merck, Pfizer, Roche, Sandoz, Janssen, AbbVie. G. Burmester: Other; AbbVie, Galapagos, Lilly, MSD, Pfizer, Roche, UCB, Janssen, Gilead Sciences, Inc. R. Westhovens: Other; Celltrion, Galapagos, Gilead. Y. Tanaka: Other; Lilly, AbbVie, Bristol Myers Squibb, Chugai, Daiichi Sankyo, Eisai, Pfizer, Mitsubishi Tanabe, GlaxoSmithKline, Asahi Kasei, Takeda, Astellas, Janssen, Novartis, Sanofi, UCB, YL Biologics, MSD, Ono, Taisho Toyama, Celltrion, Gilead, Boehringer-Ingelheim, Corrona, Kowa, Amgen, AstraZeneca, AstraZeneca, Eli Lilly.

406 Low incidence of nonmelanoma skin cancers in Taiwanese recipients of living donor liver transplants

406 Low incidence of nonmelanoma skin cancers in Taiwanese recipients of living donor liver transplants

Thiazide diuretics alone or combined with potassium-sparing diuretics to treat hypertension: a systematic review and network meta-analysis of randomized controlled trials.

The magnitude of blood pressure (BP)-lowering effects and decrease of the adverse effects of thiazide diuretics provided by potassium-sparing diuretics remain uncertain. The aim of this study was to compare the BP-lowering efficacy and the incidence of adverse effects of high (T+) and low-dose (T-) thiazide diuretics, alone or combined with high (PS+) or low-dose (PS-) potassium-sparing diuretics in patients with primary hypertension. A systematic literature search was performed in PubMed/MEDLINE, the Cochrane Central Register of Controlled Trials, Embase, Web of Science, Scopus and LILACS. Randomized double-blind placebo or active-controlled trials (RCT) with 3 weeks to 1 year of follow-up were included. Sample size, mean and standard deviation from baseline, follow-up and change from baseline values were extracted by two independent reviewers. Pairwise random effect models and Bayesian network meta-analysis models were used to compare the effects of treatments. The risk of bias in individual studies was assessed using the Rob 1.0 tool. The primary outcome was the mean difference in office SBP. Secondary outcomes were the mean difference in biochemical parameters and the incidence of nonmelanoma skin cancer. Two hundred and seventy-six double-blind RCTs involving 58 807 participants (mean age: 55 years; 45% women) were included. All treatment groups were more effective than placebo in lowering BP, with mean differences (MDs) of change from baseline ranging from -7.66 mmHg [95% credible interval (95% CrI), -8.53 to -6.79] for T- to -12.77 mmHg (95% CrI, -15.22 to -10.31) for T+PS-. T+ alone or combined with potassium-sparing was more effective in reducing BP than T-. The surface under the cumulative ranking curve (SUCRA) estimated ranking showed that the best effectiveness in lowering SBP was found for T+PS- (0.69), T+PS+ (0.65) and T+ (0.54). Compared with placebo, all treatments (except T-PS-) were associated with more potassium reduction and T+ compared with all other treatments and T- when compared with T-PS-. Compared with placebo, all active treatments (except T+PS+) showed higher elevations of uric acid. The increase of plasma glucose promoted by thiazides alone was reduced by potassium-sparing agents. Thiazides with potassium-sparing diuretics are associated with increased BP-lowering efficacy compared with thiazides alone while minimizing hypokalaemia and hyperglycaemia. These findings demonstrate that thiazide and potassium-sparing diuretic combination is preferable to thiazide alone in treating hypertension.

Cancer risks with JAKi and biological disease-modifying antirheumatic drugs in patients with rheumatoid arthritis or psoriatic arthritis: a national real-world cohort study

ObjectiveAssess cancer risks with Janus kinase inhibitors (JAKi) versus biological disease-modifying antirheumatic drugs (bDMARDs) in clinical practice.MethodsCohort study of patients with rheumatoid arthritis (RA) or psoriatic arthritis (PsA) initiating treatment...

Incidence Trends of Melanoma and Nonmelanoma Skin Cancers in Jordan From 2000 to 2016.

Skin cancers are among the commonest cancers worldwide, and the incidence of melanoma and non-melanoma skin cancer (NMSC) continues to rise worldwide. However, there are no comprehensive reports on skin cancer incidence in Jordan during the past two decades. This report investigates the incidence of skin cancers in Jordan, in particular their time trends for the period 2000-2016. Data on malignant melanomas (MMs), squamous cells carcinomas (SCCs), and basal cell carcinomas (BCCs) were extracted from the Jordan Cancer Registry for the period between 2000 and 2016. Age-specific and overall age-standardized incidence rates (ASIRs) were computed. Two thousand seventy patients were diagnosed with at least one BCC, 1,364 with SCC, and 258 with MM. ASIRs were 28, 19, and 4 per 100,000 person-years for BCC, SCC, and MM, respectively. The BCC:SCC incidence ratio was 1.47:1. The risk of men developing SCCs was significantly higher than women (relative risks [RRs], 1.311; 95% CI, 1.197 to 1.436), but significantly lower for BCCs (RR, 0.929; 95% CI, 0.877 to 0.984) or melanomas (RR, 0.465; 95% CI, 0.366 to 0.591). Persons older than 60 years were at a significantly higher risk of developing SCCs (RR, 1.225; 95% CI, 1.119 to 1.340) or melanomas (RR, 2.445; 95% CI, 1.925 to 3.104), but at a significantly lower risk of developing BCCs (RR, 0.885; 95% CI, 0.832 to 0.941). The overall incidence rates of SCCs, BCCs, and melanomas increased over the 16-year study period, but this was not statistically significant. To our knowledge, this is the largest epidemiologic study regarding skin cancers in Jordan and in the Arab world. Despite low incidence rates in this study, rates are higher than reported regional figures. This is likely due to standardized, centralized, and mandatory reporting of skin cancers, including NMSC.

Cumulative UV Exposure or a Modified SCINEXA™-Skin Aging Score Do Not Play a Substantial Role in Predicting the Risk of Developing Keratinocyte Cancers after Solid Organ Transplantation-A Case Control Study.

The risk of keratinocyte cancer is determined by intrinsic and extrinsic factors, which also influence skin aging. Few studies have linked skin aging and UV exposure with the incidence of non-melanoma skin cancer (NMSC). We evaluated signs of actinic skin damage and aging, individual UV burden, and melanocortin-1 receptor (MC1R) variants. A total of 194 organ transplant recipients (OTR) who suffered from NMSC were compared to 194 tumor-free controls matched for gender, age, type of transplanted organ, post-transplantation (TX) period, and immunosuppressive therapy. Compared with the cases, the controls scored higher in all skin aging scores and there were no differences in UV burden except for intentional whole-body UV exposure for specific UV scenarios and periods of life in favor of cases. The number of NMSCs correlated with all types of skin aging scores, the extent of intentional sun exposure, older age, longer post-TX period, shorter interval from TX to first NMSC, and specific MC1R risk groups. Multivariable models revealed a 7.5-fold risk of developing NMSC in individuals with actinic keratosis; 4.1- or 3.6-fold in those with green or blue eyes, respectively; and a 1.9-fold increased risk in the MC1R medium- + high-risk group. In the absence of skin aging contributing to NMSC development, certain MC1R risk types may identify OTR at risk for high tumor burden.

The Prevalence and Treatment Costs of Non-Melanoma Skin Cancer in Cluj-Napoca Maxillofacial Center

Background and Objectives: An increasing incidence of non-melanoma skin cancer (NMSC) is noted, as well as an increasing cost of the treatment, with NMSC becoming a public health problem. We aimed to investigate the prevalence and treatment costs of surgically treated NMSC from the Oral and Maxillofacial Surgery Department of Cluj-Napoca County Hospital. Materials and Methods: We retrospectively analyzed the clinical data and the charge data of hospitalization from the informatic system of Cluj-Napoca County Hospital. All patients benefited from standard surgical excision with the reconstruction of the post-excisional defect. A statistical analysis of the costs related to the patients' features, period and conditions of hospitalization, materials, medication, and paraclinical investigations was performed. Results: Between 2015 and 2019, 133 patients with NMSC were addressed to our department, with basal cell carcinoma (BCC) being four-fold higher than squamous cell carcinoma (SCC). Most NMSC cases were diagnosed in stage I or II, and they benefited from local reconstruction. The treatment costs progressively increased in the last five years, reaching a total cost of EUR ~13.000 in 2019. The treatment cost per episode was higher for SCC compared to BCC, while the total cost of treatment in 5 years was higher for BCC. Low income, immunosuppression, comorbidities, flap reconstruction option, long-lasting surgery, and prolonged hospitalization were associated with an increased cost of the treatment. Conclusion: The prevalence and treatment cost of surgically treated NMSC of the head and neck region increased in the last five years, with high-cost drivers being related to patients and treatment options.