The Role of Inhalant Allergens on the Clinical Manifestations of Atopic Dermatitis.

BACKGROUND: Inhalant allergens provide a source of environmental factors that contribute to the development of clinical symptoms in patients with atopic dermatitis (AD). OBJECTIVE: To review the relationship between inhalant allergens and AD. METHODS: A literature review was conducted using three databases: PubMed/MEDLINE, ClinicalKey, and Web of Science. Search terms, including "atopic dermatitis," "atopic eczema," and "eczema," were used in combination with "inhalant allergen," "inhaled allergen," and "aeroallergen" to identify relevant published manuscripts that highlight the relationship between AD and exposures to inhalant allergens. RESULTS: Fifteen articles were suitable for review. The studies included in the review investigated the effect of inhalant allergens on the clinical manifestations of AD through bronchial provocation, direct skin contact, and allergen sensitization. CONCLUSION: There is a significant relationship between exposures to inhalant allergens and AD. Inhalant allergens may aggravate AD symptoms by either bronchial provocation or direct skin contact. Sensitization of inhalant allergens, mainly house dust mites, follows a specific age-related pattern.

CT109-SN-38, a Novel Antibody-drug Conjugate with Dual Specificity for CEACAM5 and 6, Elicits Potent Killing of Pancreatic Cancer Cells.

BACKGROUND: CEACAM5 and CEACAM6 are glycosylphosphatidylinositol (GPI)- linked members of the carcinoembryonic antigen-related cell adhesion molecule (CEACAM) family, which are frequently upregulated in epithelial cancers where they contribute to invasion, metastasis, immune evasion, and resistance to anoikis. CT109 is a novel antibody with dual specificity to both CEACAM5 and 6. OBJECTIVES: In this study, we aimed to perform the preclinical characterization of CT109 and antibody- drug conjugate (ADCs) derivatives of CT109, focusing on CT109-SN-38. METHODS: CT109's cognate epitope was characterized by scanning mutagenesis. CT109 specificity and internalization kinetics were assessed by immunoblot and flow cytometry, respectively. Cognate antigen expression prevalence in colorectal cancer and normal tissue arrays was determined by immunohistochemistry. CT109 conjugations were generated by the reaction of reduced CT109 cysteines with maleimide-functionalized payload linkers. In vitro cytotoxic activity of CT109 ADCs was characterized on antigen-positive and negative pancreatic ductal adenocarcinoma cell (PDAC) lines using a luminometric viability assay. In vivo efficacy of CT109-SN-38 was assessed on a PDAC tumor xenograft model at 10 and 25 mg/kg concentrations. RESULTS: CT109 was shown to bind a glycoepitope centered on N309. CT109 is internalized in the CEACAM5+/CEACAM6+ double-positive PDAC line, BxPC-3, with a t1/2 of 2.3 hours. CT109 ADCs elicit a dose and antigen-dependent cytotoxic effect, with CT109-SN-38 exhibiting an IC50 value of 21 nM in BxPC-3 cells. In a BxPC-3 tumor xenograft model, CT109-SN-38 reduced tumor growth and induced regression in 3/10 mice at a concentration 25 mg/kg. CONCLUSION: These data suggest that further preclinical and clinical development of CT109-SN-38 is warranted.

Proportions of Biologic Discontinuation Among Psoriasis Patients With Metabolic Comorbidities.

Background: Among psoriasis patients, the presence of metabolic comorbidities associates with poorer response to biologics. How the presence of comorbidity impacts treatment patterns with biologics is not fully understood. Methods: Adult patients in the CorEvitas Psoriasis Registry were included if they initiated biologic therapy between 5/2015-12/2019 and had a 6-month follow-up visit. The frequency of biologic discontinuations by 6-months were calculated by metabolic comorbidity status (current obesity and histories of hypertension [HTN], diabetes [DM], and hyperlipidemia [HLD]) for all patients and by drug class (tumor necrosis factor inhibitors [TNFi], interleukin-17i [IL-17i], and IL-23i or IL-12/23i). Results: Among the 2924 participants, discontinuations were more frequent in those with obesity (17%, P < .01) or DM (20%, P < .001) compared to those without these (13% and 14%, respectively). Discontinuations were similar for those with and without histories of HTN or HLD. Frequencies of discontinuation for each biologic class were: TNFi (26%), IL-17i (16%), and IL-23i or IL-12/23i (9%). Among TNFi initiators, the proportions of discontinuations were greater in the presence of obesity (30%, P < .05), DM (34%, P < .05), or HTN (34%, P < .01) compared to those without (22%, 24%, and 22%, respectively). Of the IL-23i or IL-12/23i initiators, discontinuations were more frequent in those with obesity (11%, P < .01) or with DM (13%, P < .05) compared to those without (7% and 8%, respectively). Discontinuations did not statistically differ between comorbidity groups in IL-17i initiators. Conclusion: Comorbid disease status, especially obesity and DM, should be assessed at biologic initiation as it may predict a less optimal clinical outcome.

Cardiometabolic multimorbidity is common among patients with psoriasis and is associated with poorer outcomes compared to those without comorbidity.

BACKGROUND: Associations between cardiometabolic multimorbidity and response to therapy in psoriasis are unknown. OBJECTIVE: Determine the associations of multimorbidity with response to biologic treatment in psoriasis patients. METHODS: CorEvitas Psoriasis Registry participants who initiated biologic therapy and had 6-month follow-up were stratified by 0, 1, 2+ comorbidities (diabetes, hypertension, hyperlipidemia). Adjusted odds ratios (95% CIs) were calculated overall and separately by biologic class (TNFi, IL-17i, IL-12/23i + IL-23i), to assess the likelihood of achieving response for the 1 and 2+ groups vs. 0. RESULTS: Of 2,923 patients, 49.5%, 24.7% and 25.8% reported 0, 1 and 2+ comorbidities, respectively. Overall, likelihood of PASI75 was 18% (OR = 0.82; 95%CI: 0.67, 1.00) and 23% (OR = 0.77; 95%CI: 0.63, 0.96) lower in those with 1 and 2+ comorbidities, respectively, vs. 0. In those who initiated IL-17i, odds of PASI75 and PAS90 were 34% (OR = 0.66; 95%CI: 0.48-0.91) and 35% (OR = 0.65; 95%CI: 0.47-0.91) lower in the 2+ multimorbidity cohort. No significant associations were found among users of TNFi or IL-12/23i + IL-23i groups in the multimorbidity group. LIMITATIONS: Patients may not be representative of all psoriasis patients. CONCLUSION: Multimorbidity in psoriasis may decrease the likelihood of achieving treatment response to biologic therapy and should be considered when discussing treatment expectations with patients.

Comorbid obesity and history of diabetes are independently associated with poorer treatment response to biologics at 6 months: A prospective analysis in Corrona Psoriasis Registry.

BACKGROUND: Psoriasis is associated with comorbid systemic metabolic disease. OBJECTIVE: To assess possible associations of comorbid obesity, history of diabetes, hypertension, and hyperlipidemia with response to biologic treatment at 6 months among patients in CorEvitas' Psoriasis Registry. METHODS: Participants included 2924 patients initiating biologic therapy (tumour necrosis factor inhibitors [TNFi], interleukin [IL]-17i, IL-12/23i, or IL-23i) with baseline and 6-month follow-up visits available. Logistic regressions resulted in adjusted odd ratios (OR) and 95% confidence intervals (CI) for achievement of response in select outcomes for those with obesity and history of diabetes, hypertension, and hyperlipidemia relative to those without each. RESULTS: Overall, obesity reduced by 25% to 30% odds of achieving PASI75 (OR, 0.75; 95% CI, 0.64-0.88) and PASI90 (OR, 0.70; 95% CI, 0.59-0.81). History of diabetes reduced odds of achieving PASI75 by 31% (OR, 0.69; 95% CI, 0.56-0.85) and PASI90 by 21% (OR, 0.79; 95% CI, 0.63-0.98). Obesity was associated with lower response to TNFi and IL-17i classes. Independent of obesity, diabetes was associated with poorer outcomes when on IL-17i therapy and hypertension, to a lesser extent, when on the TNFi class. No significant associations were found in the hyperlipidemia group. LIMITATIONS: The study assessed only short-term effectiveness and small sample sizes limited the power to detect differences. CONCLUSION: Assessment of comorbid disease burden is important for improved likelihoods of achieving treatment response with biologics.

Geographic Patterns in Psoriasis: An Observational Study of CorEvitas Psoriasis Registry.

Background: How psoriasis disease characteristics, management, and outcomes each vary across the US is not fully understood. Objective: Assess regional disease characteristics for patients enrolled in CorEvitas Psoriasis Registry, report biologic initiations by class over the period, and evaluate regional outcome data for initiations with 6-month follow-up. Methods: Participants included new biologic initiations in CorEvitas Psoriasis Registry from 2014-2019 categorized into 7 different geographic regions: Northeast, East North Central, Mountain/West North Central, South Atlantic, East South Central, West South Central, and Pacific. Baseline demographics and disease characteristics are described by region. For participants with 6-month follow-up data, we report treatment patterns and treatment outcomes. Results: 7520 biologic initiations from 6320 patients were available. Over time, biologic initiations in most US regions within the Registry resulted in a pattern where IL-17 inhibitors were used most frequently, followed by IL-12/23 and IL-23 inhibitors, and lastly by TNF inhibitors. Baseline disease severity varied among regions with the East South Central reporting the largest proportion (25.1%) of very severe disease by body surface area. Frequencies of metabolic comorbid diseases varied between regions (obesity, diabetes, hyperlipidemia, each P < .001; hypertension P < .019), with the East South Central reporting the largest proportions. Rates of achieving PASI75 and IGA 0/1 varied at 6-months (P = .008 and P = .001, respectively), with the East South Central reporting the lowest frequencies. At 6-months 28.2% of biologic initiations in the East South Central were discontinued, of which 22% had switched to another therapy. Conclusion: Providers should be aware of regional trends in disease characteristics to improve overall care of psoriasis patients.

Psoriasis Severity, Comorbidities, and Treatment Response Differ among Geographic Regions in the United States.

Little is known about how psoriatic disease characteristics and treatment outcomes differ geographically in the United States. Our aim was to explore real-world, geographic variations in the use of biologic classes and outcomes within the Corrona Psoriasis Registry. Patient demographics and disease characteristics were assessed at biologic initiation and at 6 months. Logistic regressions were conducted to evaluate the odds of achieving targeted outcomes for seven United States geographic regions. We examined 737 biologic initiations among 717 patients. IL-17 inhibitors were used most frequently (45%), followed by IL-12‒IL-23 and IL-23 inhibitors (38%) and TNF inhibitors (17%). The proportions of patients with obesity (body mass index > 30) and very severe psoriasis (body surface area > 20) were greatest in the East South Central and West South Central regions. After adjusting for age, sex, race, body mass index, and baseline body surface area, decreased odds of achieving 75% improvement in PASI at 6 months were observed among patients in the East South Central (OR = 0.47, 95% confidence interval = 0.28-0.79, P = 0.004), West South Central (OR = 0.43, 95% confidence interval = 0.22-0.87, P = 0.019), and Pacific (OR = 0.49, 95% confidence interval = 0.28-0.84, P = 0.010) regions compared with those observed among patients in the Northeast. The East South Central and West South Central regions may have the greatest frequencies of very severe disease burden and, along with the Pacific region, may be less likely to achieve targeted response within 6 months of initiating biologic therapy.

Sun-protection Behaviors Among Active Members of the United States Lifesaving Association.

BACKGROUND: Ultraviolet radiation exposure is the most prominent modifible risk factor for developing both melanoma and non-melanoma skin cancers. OBJECTIVE: We sought to elucidate sun-protective behaviors among active members of the United States Lifesaving Association (USLA), a nationwide nonprofit organization comprising beach lifeguards, and to identify positive and negative predictors of sun protective behaviors. METHODS: This was a pilot, cross-sectional survey study. All USLA lifeguards aged 18 years or older were invited to complete a 19-item survey. Data were collected anonymously at the 2018 USLA National Lifeguard Championships in Virginia Beach, Virginia. Participant characteristics and sun-protective behaviors (e.g., hat, sunglasses, protective clothing, sunscreen, and seeking shade) were surveyed. A composite score (0-10 points) was created based on sun-protective behaviors. Simple linear regression models were fit to assess the relationship between lifeguard characteristics and the sun-behavior composite score and a multiple linear regression model was used to assess their overall positive or negative effect on composite scores. RESULTS: A total of 215 USLA lifeguards completed the survey study; of these, 64.2% were male and the average age was 34.2 years. The most common sun-protective behavior was wearing sunglasses (85%), followed by applying sunscreen (65%), wearing a hat (46.7%), seeking shade (38.6%), and wearing protective clothing (34.0%). The overall average composite score was 7.5±1.9 points. In the multiple linear regression model, female sex (ß=-0.85; p=0.0012), desiring a tan (ß=-1.26; p=0.0008), and working more summer daytime hours (ß=-0.49; p=0.049) negatively impacted composite scores. CONCLUSIONS: USLA beach lifeguards are subject to sun-exposure patterns and practiced sun-protective behaviors that potentially place them at higher risk for skin cancer.

Management of psoriasis in patients with inflammatory bowel disease: From the Medical Board of the National Psoriasis Foundation.

BACKGROUND: There is a significant association between psoriasis and inflammatory bowel disease (IBD). Many treatments for psoriasis and psoriatic arthritis are also used for IBD. OBJECTIVE: To assess therapeutic options for patients with psoriasis and concurrent IBD. METHODS: A systematic literature search was performed for clinical studies of biologic and systemic psoriasis medications in psoriasis, psoriatic arthritis, ulcerative colitis, and Crohn's disease, for the period from January 1, 1947, to February 14, 2017. Randomized, controlled, double-blinded studies were selected if available. If not, the next highest level of available evidence was selected. RESULTS: Of the 2282 articles identified, 132 were selected. Infliximab and adalimumab have demonstrated efficacy in psoriasis, psoriatic arthritis, ulcerative; colitis, and Crohn's disease. Ustekinumab has demonstrated efficacy in psoriasis, psoriatic arthritis, and Crohn's disease. Certolizumab has demonstrated efficacy in psoriatic arthritis and Crohn's disease. Etanercept, secukinumab, brodalumab, and ixekizumab have demonstrated efficacy in psoriasis and psoriatic arthritis but may exacerbate or induce IBD. Guselkumab has demonstrated efficacy in psoriasis. LIMITATIONS: There are no known clinical trials of treatment specifically for concurrent psoriasis and IBD. CONCLUSIONS: Infliximab and adalimumab have demonstrated efficacy in psoriasis, psoriatic arthritis, ulcerative colitis, and Crohn's disease; other agents have demonstrated efficacy for some, but not all, of these indications.

From Bench to Bedside: The Hampton University Skin of Color Research Institute 2015 Skin of Color Symposium.

The Hampton University Skin of Color Research Institute Skin of Color Symposium 2015: From Bench to Bedside was held in Williamsburg, Virginia at the Williamsburg Lodge, November 13-15, 2015. The conference was designed to promote, develop, and advance the education, knowledge, and research of cutaneous disorders disproportionately affecting people of racial and ethnic minority groups. Centered on the theme of "From Bench to Bedside", the symposium provided a program featuring a diverse panel of nationally recognized physician-scientists, basic scientists, and clinicians who updated attendees on the latest research advances across multiple relevant disciplines, including public health, basic science, and the clinical diagnosis and management of select complex and rare dermatologic conditions. Featured sessions included recent advances in vitiligo, disorders of hyperpigmentation, keloids, central centripetal cicatricial alopecia, and cutaneous lupus. We expect that the scientific sessions and interactive panel discussions, combined with the synergistic environment that has characterized this conference, will spur the formation of new collaborations and scientific discovery and, ultimately, will culminate in novel treatments for dermatologic disorders disproportionately affecting individuals with skin of color.