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.

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.

Discriminating the hemolytic risk of blood type A plasmas using the complement hemolysis using human erythrocytes (CHUHE) assay.

BACKGROUND: The agglutination-based cross-matching method is sensitive for antibody binding to red blood cells but is only partially predictive of complement-mediated hemolysis, which is important in many acute hemolytic transfusion reactions. Here, we describe complement hemolysis using human erythrocytes (CHUHE) assays that directly evaluate complement-mediated hemolysis between individual serum-plasma and red blood cell combinations. The CHUHE assay is used to evaluate correlations between agglutination titers and complement-mediated hemolysis as well as the hemolytic potential of plasma from type A blood donors. STUDY DESIGN AND METHODS: Plasma or serum from each type A blood donor was incubated with AB or B red blood cells in the CHUHE assay and measured for free hemoglobin release. RESULTS: CHUHE assays for serum or plasma demonstrate a wide, dynamic range and high sensitivity for complement-mediated hemolysis for individual serum/plasma and red blood cell combinations. CHUHE results suggest that agglutination assays alone are only moderately predictive of complement-mediated hemolysis. CHUHE results also suggest that plasma from particular type A blood donors produce minimal complement-mediated hemolysis, whereas plasma from other type A blood donors produce moderate to high-level complement-mediated hemolysis, depending on the red blood cell donor. CONCLUSION: The current results indicate that the CHUHE assay can be used to assess complement-mediated hemolysis for plasma or serum from a type A blood donor, providing additional risk discrimination over agglutination titers alone.

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.

Diversity in Dermatology Residency Programs.

Given the change in our population to one that is more racially and ethnically diverse, the topic of diversity in dermatology residency programs has gained attention. In a field that has become highly competitive, diversity is lagging behind. What are the reasons for this? The existing diversity among medical school matriculants is reflective of the applicant pool, and although modest, there has been an increase in applications and acceptances from minority populations. However, these proportions do not carry through to the population applying to dermatology residency. Making sense of this and planning how to recruit a more diverse applicant pool will improve the quality and cultural competency of future dermatologists.

Contact dermatitis: a historical perspective.

Contact dermatitis is a common skin condition that can have a considerable impact on patient quality of life and function. Historically, contact dermatitis has played a significant role in the evolution of dermatology as the understanding of a relationship between environmental exposure and specific skin disease became more widely accepted. Reports about this relationship can be found throughout the history of humanity, thousands of years ago. The Egyptians were perhaps the first to document this relationship in ancient history, and documentation has also been found in several other cultures and nations such as the Chinese, Indians, Europeans, and American colonizers. The patch test emerged over a century ago and has remained a powerful tool for diagnosing and directing patients. This paper provides historical and curious facts about contact dermatitis.

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.

The Effects of Cardiometabolic Comorbidities on Biologic Treatment for Psoriasis with Respect to PASI Scores: A Qualitative Systematic Review.

Objective: Cardiometabolic risk factors have been shown to decrease biologic efficacy in patients treated for inflammatory conditions. The purpose of this systematic review is to provide a qualitative evaluation of studies investigating biologic response among psoriasis patients with cardiometabolic comorbidities. Methods: A comprehensive review was conducted according to the Preferred Reporting Guidelines for Systematic Reviews and Meta-Analysis guidelines to screen for studies including patients with cardiometabolic risk factors receiving biologic therapy for psoriasis. Studies not including a Psoriasis Area and Severity Index (PASI) score to evaluate treatment outcomes were not included. All studies underwent quality/bias analysis using the Methodological Index for Non-Randomized Studies (MINORS) scale. Results: Obesity and Body Mass Index (BMI) were the most studied cardiometabolic risk factors. The majority of the studies reported a lower frequency of achieving PASI75 and PASI90 response with increasing BMI/obesity rates. Diabetes and hypertension showed similar findings but were not studied as frequently. Hyperlipidemia and other lipid disorders were less frequently studied. Conclusion: Relationships between cardiometabolic risk factors and lower frequencies of achieving PASI75/90 exist in current literature. This qualitative systematic review reports evidence of lower PASI75 and PASI90 response rates in the presence of cardiometabolic risk factors.

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.

Physical activity engagement and responses to exercise in plaque psoriasis: a multifactorial investigation of influential factors.

BACKGROUND: Psoriasis may increase the risk of physical inactivity, but few studies have evaluated the etiology. OBJECTIVE: To identify barriers to and predictors of physical activity in psoriasis. METHODS: Twenty individuals with psoriasis (PsO) and 23 controls recorded activity with accelerometers and completed self-paced 20-min treadmill bouts. Questionnaires on self-efficacy for exercise (SEE), pruritus, and dermatology life quality index (DLQI) were completed. Psoriasis severity was measured via body surface area (BSA), psoriasis area and severity index (PASI), and investigator's global assessment (IGA). RESULTS: No differences in moderate-vigorous activity existed between PsO and controls (ANCOVA means: 26 ± 4 versus 27 ± 4 min, p = .802). Relative to controls, PsO selected treadmill speeds that were 13-18% slower and experienced more pruritus while exercising. Among the PsO group, PASI, BSA, IGA, and DLQI showed inverse correlations with vigorous activity (partial rhos= -0.55 to -0.62, p < .05). Likewise, BSA, IGA, DLQI, and pruritus were inversely correlated with footsteps (partial rhos= -0.47 to -0.62, p < .05). SEE was consistently positively correlated with activity levels among PsO (partial rhos ≥0.60 for moderate activity, vigorous activity, and footsteps). CONCLUSION: Individuals with extensive psoriasis and poorer SEE engage in less vigorous activity and take fewer footsteps. Among other factors, pruritus is a novel explanation.

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.