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Katherine A Kelly,1 Patrick O Perche,1 Steven R Feldman1– 4 1Center for Dermatology Research, Department of Dermatology, Wake Forest School of Medicine, Winston-Salem, NC, USA; 2Department of Pathology, Wake Forest School of Medicine, Winston-Salem, NC, USA; 3Department of Social Sciences & Health Policy, Wake Forest School of Medicine, Winston-Salem, NC, USA; 4Department of Dermatology, University of Southern Denmark, Odense, DenmarkCorrespondence: Steven R Feldman, Department of Dermatology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC, 27157-1071, USA, Tel +1 336-716-7740, Fax +1 336-716-7732, Email sfeldman@wakehealth.eduAbstract: Atopic dermatitis (AD) is a chronic inflammatory skin disease that greatly impacts patient quality of life. Type 2 cytokine interleukin (IL)-13 is integral to the pathogenesis of AD. Tralokinumab is a fully human IgG4 monoclonal antibody that specifically targets IL-13, preventing downstream signaling of inflammatory pathways that may contribute to AD. Tralokinumab was US Food and Drug administration (FDA) recently approved for the treatment of moderate to severe AD on December 28, 2021. In our review, we will explore the efficacy and adverse effects (AEs) of tralokinumab for the treatment of patients with moderate to severe AD. A PubMed search for key articles on the emerging clinical data of tralokinumab was performed. Six randomized controlled trials of tralokinumab identified improvements in disease severity measures, including Investigator’s Global Assessment (IGA) scores and Eczema Area Severity Index 75 (EASI75) scores. Four of these studies demonstrated improvements in quality of life measures with tralokinumab, including pruritus scores, sleep interference scores, Dermatology Life Quality Index, SCORing Atopic Dermatitis (SCORAD), Patient Oriented Eczema Measure, and The Short Form 36 Health Survey (SF-36v2) scores. One study identified a similar immune response in patients taking tralokinumab to those taking the Tdap and meningococcal vaccines. Upper respiratory infection, conjunctivitis, and headaches were the most common adverse events. The varying criteria to assess changes in AD disease severity across different studies is a limitation of this review. Tralokinumab is another promising biologic option for the treatment of moderate to severe AD, which may reduce disease burden and improve patient quality of life.Keywords: biosimilar, biologic, non-medical switching, real-world data

Jeremy G Light,1 Jennifer J Su,1 Steven R Feldman1– 4 1Center for Dermatology Research, Department of Dermatology, Wake Forest School of Medicine, Winston-Salem, NC, USA; 2Department of Pathology, Wake Forest School of Medicine, Winston-Salem, NC, USA; 3Department of Social Sciences & Health Policy, Wake Forest School of Medicine, Winston-Salem, NC, USA; 4Department of Dermatology, University of Southern Denmark, Odense, DenmarkCorrespondence: Jeremy G LightDepartment of Dermatology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1071, USATel +1 336-716-7740Fax +1 336-716-7732Email jlight2020@gmail.comAbstract: Psoriasis is a chronic immune-mediated disease involving complex interaction of T cells and keratinocytes. The comprehensive pathogenesis of psoriasis is not fully understood but the IL-23/Th17 axis is a central pathway in driving disease development. Guselkumab is the first treatment of moderate-to-severe psoriasis that specifically targets the p19 subunit of IL-23. The benefit of guselkumab has been established by a number of clinical trials including demonstration of greater long-term efficacy in recent comparator trials. This review addresses the results of head-to-head trials (ECLIPSE, IXORA-R, and POLARIS) that compared guselkumab to secukinumab, ixekizumab, and fumaric acid esters. The previously demonstrated long-term efficacy of guselkumab has been corroborated by many recently published studies. The effective and safe profile, convenient dosing, and improved quality of life in patients make gulselkumab a viable first-line treatment option for moderate-to-severe psoriasis.Keywords: guselkumab, psoriasis, biologics, efficacy, interleukin-23

Rhea Singh,1 Courtney E Heron,1 Rima I Ghamrawi,1 Lindsay C Strowd,1 Steven R Feldman1– 4 1Center for Dermatology Research, Department of Dermatology, Wake Forest School of Medicine, Winston-Salem, NC, USA; 2Department of Pathology, Wake Forest School of Medicine, Winston-Salem, NC, USA; 3Department of Social Sciences & Health Policy, Wake Forest School of Medicine, Winston-Salem, NC, USA; 4Department of Dermatology, University of Southern Denmark, Odense, DenmarkCorrespondence: Rhea SinghDepartment of Dermatology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1071, USATel +1 336-716-7740Fax +1 336-716-7732Email rsingh5@vcu.eduBackground: Atopic dermatitis (AD) is a common chronic, inflammatory skin condition. The pathogenesis of AD involves many cytokines that utilize the Janus kinase/signal transducer and activator of transcription (JAK-STAT) signaling cascade; therefore, JAK inhibitors may be used in the treatment of AD. This review aims to evaluate the pathophysiology, efficacy, and safety of JAK inhibitors and their emerging role as a therapeutic option for patients with AD.Methods: A PubMed search of Phase I, II, and III clinical trials was conducted for relevant literature published between January 2015 and June 2020 utilizing the key terms: JAK inhibitors, atopic dermatitis, efficacy, safety, and treatment. The search was subsequently expanded to include additional terms.Results: In multiple Phase II and III clinical trials, JAK inhibitors were more efficacious than placebo or vehicle controls and slightly more efficacious in direct comparisons to corticosteroids. Overall, JAK inhibitors have a moderate safety profile for use in AD. Some of the more severe theoretical adverse events included thrombosis and reactivation of viral infections. While data remain limited for the long-term efficacy and safety of JAK inhibitor use in patients with AD, many ongoing clinical trials have promising preliminary results.Discussion: Short-term data suggest that both topical and oral JAK inhibitors are efficacious and safe for use in patients with AD, although cases of thrombosis and viral disease have been reported. While the current standard treatments for AD are likely preferred, failed therapy with these agents or corticosteroid phobia may be indications for the use of JAK inhibitors in patients with AD.Keywords: atopic dermatitis, eczema area and severity index, Janus kinase inhibitor, pruritus

Elias Oussedik1,2, Abigail Cline1, Jennifer J Su1, EJ Masicampo3, Lara K Kammrath3, Edward Ip4, Steven R Feldman1,5,6 1Center for Dermatology Research, Department of Dermatology, Wake Forest School of Medicine, Winston-Salem, NC, USA; 2Faculty of Medicine, McGill University, Montreal, QC, Canada; 3Department of Psychology, Wake Forest University, Winston-Salem, NC, USA; 4Department of Pathology, Wake Forest School of Medicine, Winston-Salem, NC, USA; 5Department of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA; 6Department of Dermatology, University of Southern Denmark, Odense, DenmarkCorrespondence: Abigail ClineCenter for Dermatology Resarch, Department of Dermatology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1071, USATel +1 336 716 7740Fax +1 336 716 7732Email aecline25@gmail.comBackground: The accountability inherent in the social interaction between a patient and healthcare provider affects patients’ motivation to adhere to treatment. To characterize the role of accountability as a tool to improve self-efficacy and self-management and thereby promote patients’ adherence to treatment, a measure of accountability is needed.Aims: To develop and test the validity, reliability, and sensitivity of a new outcome measure designed to assess accountability.Methods: The accountability measurement tool was developed from the literature, expert consultation, and focus groups. A focus group and three pilot studies were performed both in clinic and through an online crowdsourcing platform. Principal Component Analysis evaluated constructs, and Cronbach’s alpha measured internal consistency. Validity was established using convergent and divergent correlations to other validated scales.Results: A total of 292 participants took part in this study. The 12-item accountability scale demonstrated very good internal consistency (Cronbach’s α=0.92). Components of the accountability measurement tool correlated with predicted validated measures, including the Treatment Self-Regulation Questionnaire. Divergent validity was established with no significant difference noted between age, sex, race, and education level.Conclusion: Future use of this questionnaire will allow for the assessment of the interaction between accountability and adherence to treatment and lead to the development of new interventions to promote better adherence.Keywords: accountability, adherence, self-determination theory, self-efficacy, patient behavior

Todd Wechter,1 Abigail Cline,2 Steven R Feldman2–4 1Stony Brook Medicine, Stony Brook, NY, USA; 2Center for Dermatology Research, Department of Dermatology, Wake Forest School of Medicine, Winston-Salem, NC, USA; 3Department of Pathology, Wake Forest School of Medicine, Winston-Salem, NC, USA; 4Department of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA Abstract: Further understanding of psoriasis pathogenesis has led to the development of effective biologic medications. Guselkumab (GUS) is a subcutaneously administered monoclonal antibody that targets the p19 cytokine subunit in IL-23 and IL-39 and is US Food and Drug Administration (FDA) approved for the treatment of moderate-to-severe psoriasis in adult patients. This review evaluates the pharmacology, safety and efficacy of GUS in patients with psoriasis. We performed a literature review by searching online databases including PubMed and Google Scholar. In clinical trials, GUS improved diseases including psoriatic arthritis (PsA) and specific areas of disease (scalp, feet, hands and fingernails). In the Phase III trials VOYAGE 1 and 2, more GUS than adalimumab (ADM) patients experienced a ≥90% reduction in Psoriasis Area and Severity Index (PASI) score (PASI90) (VOYAGE 1: 80.2% vs 53.0%; VOYAGE 2: 75.2% vs 54.8%; P

Isha Patel,1,* Travis Chapman,2,* Fabian Camacho,3 Shameen Shrestha,4 Jongwha Chang,5 Rajesh Balkrishnan,3 Steven R Feldman6 1Department of Pharmacy Practice, Administration and Research, Marshall University School of Pharmacy (MUSOP), Marshall University, Huntington, WV, USA; 2Walgreens DBA Rite Aid, Winchester, VA, USA; 3Department of Department of Public Health Sciences, School of Medicine, University of Virginia, Charlottesville, VA, USA; 4Bernard J Dunn School of Pharmacy, Shenandoah University, Winchester, VA, USA; 5Department of Pharmacy Practice and Clinical Sciences, School of Pharmacy, University of Texas at El Paso, El Paso, TX, USA; 6Department of Dermatology, Pathology and Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, USA *These authors contributed equally to this work Background: There is a lack of research in the USA comparing patient satisfaction with pediatricians and other primary care physicians (PCPs). We examined and compared patient satisfaction toward their pediatricians and PCPs and characterized factors associated with higher patient satisfaction in these two groups. Methods: A random coefficient model with random slope and intercept was fit to the data, with patient satisfaction as a function of pediatrician/PCP, covariates, and physician random effects. Effect heterogeneity was assessed by allowing slope to vary as a function of covariates. Mediation analysis using the random coefficient model was conducted to calculate average total effect, average natural direct effect, and average indirect effect of pediatrician/PCP on satisfaction mediated by waiting/visit times. Results: Pediatricians had higher predicted satisfaction ratings than PCPs (total effect = 4.8, 95% CI 3.7–5.9), with population-averaged mean of 82.2 (0.54) vs 77.4 (0.13). The direct effect was 3.9 (2.8–5.0) and the indirect effect was 0.9 (0.9–0.9), suggesting that part but not all of the total effect can be explained by pediatricians having decreased waiting/visit times leading to increased satisfaction. Predictions by subgroup suggested that pediatricians had lower ratings than PCPs for first visit, but higher ratings for all other covariate strata considered. Having longer waiting times and decreased visit times coincided with closer mean ratings between pediatricians and PCPs, other significant effect modifiers included patient sex, provider sex, and region of practice. Conclusion: Pediatricians scored higher patient satisfaction ratings than the combined group of other PCPs. Pediatricians had shorter wait times to see their patients compared to PCPs. Shorter wait times and longer visit times were associated with higher patient satisfaction ratings. Keywords: patient satisfaction, waiting time, office visits, surveys, questionnaires, humans

Mwangi J Murage,1 Vanita Tongbram,2 Steven R Feldman,3 William N Malatestinic,1 Cynthia J Larmore,1 Talia M Muram,1 Russel T Burge,1,4 Charles Bay,2 Nicole Johnson,2 Sarah Clifford,5 Andre B Araujo1 1Eli Lilly and Company, Indianapolis, IN, USA; 2ICON Plc, New York, NY, USA; 3Wake Forest University School of Medicine, Winston-Salem, NC, USA; 4University of Cincinnati, Division of Pharmaceutical Sciences, Winkle College of Pharmacy, Cincinnati, OH, USA; 5ICON Plc, San Francisco, CA, USA Purpose: Proper adherence and persistence to medications are crucial for better quality of life and improved outcomes in rheumatoid arthritis (RA), psoriasis (PsO), and psoriatic arthritis (PsA). We systematically describe current adherence and persistence patterns for RA, PsO, and PsA, with a focus on biologics and identifying factors associated with adherence and persistence. Patients and methods: Using various databases, a systematic literature review of US-based studies published from 2000 to 2015 on medication adherence and persistence to biologics and associated factors was conducted among patients with RA, PsO, and PsA. Results: Using the medication possession ratio or the percentage of days covered >80%, RA and PsO adherence rates for etanercept, adalimumab, and infliximab ranged from 16% to 73%, 21% to 70%, and 38% to 81%, respectively. Using the criteria of a ≥45-day gap, RA persistence rates for etanercept, adalimumab, and infliximab ranged from 46% to 89%, 42% to 94%, and 41% to 76%, respectively. In PsO, persistence rates for etanercept and adalimumab ranged from 34% to 50% and 50% to 62%, respectively. Similar persistence rates were observed in PsA. Experienced biologics users showed better adherence and persistence. Younger age, female gender, higher out-of-pocket costs, greater disease severity, and more comorbidities were associated with lower adherence and persistence rates. Qualitative surveys revealed that nonpersistence was partly due to perceived ineffectiveness and safety/tolerability concerns. Conclusion: Biologic adherence and persistence rates in RA, PsO, and PsA in the United States were low, with significant opportunity for improvement. Various factors – including decrease in disease severity; reduction of comorbidities; lower out-of-pocket costs; refilling at specialty pharmacies; and awareness of drug effectiveness, safety, and tolerability – can inform targeted approaches to improve these rates. Keywords: biologics, compliance, nonadherence, nonpersistence, factors, discontinuation

Nupur U Patel,1 Catherine Roach,1 Hossein Alinia,1 William W Huang,1 Steven R Feldman1–3 1Department of Dermatology, Center for Dermatology Research, Wake Forest University School of Medicine, Winston-Salem, NC, 2Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, NC, 3Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, USA Abstract: Acanthosis nigricans (AN) is a common dermatologic manifestation of systemic disease that is associated with insulin resistance, diabetes mellitus, obesity, internal malignancy, endocrine disorders, and drug reactions. Treatment of AN primarily focuses on resolution of the underlying disease processes causing the velvety, hyperpigmented, hyperkeratotic plaques found on the skin. While the goal of therapy is to treat the primary cause, cosmetic resolution of AN lesions can be important for patients and their quality of life. Treatment options for AN have not been extensively studied; however, smaller powered clinical trials and case reports exist in the literature. Our review aims to explore and evaluate the current treatment options that exist for AN. Keywords: acanthosis nigricans, diabetes, obesity, hyperinsulinemia, dermatologic condition, dermatology, malignant acanthosis, pseudoacanthosis, metformin, isotretinoin, tretinoin, topical therapy

Francesca Devine,1 Taylor Edwards,1 Steven R Feldman1–3 1Center for Dermatology Research, Department of Dermatology, 2Department of Pathology, 3Department of Social Sciences & Health Policy, Wake Forest School of Medicine, Winston-Salem, NC, USA Background: Poor adherence is the result of many barriers. Most of the adherence research has focused on the patients’ hurdles to adherence, instead of the responsibility the physician has for assuring adherence to treatment.Objective: The purpose of this review is to identify barriers to medication adherence and refocus how we describe those barriers in terms of physician behavior hurdles.Methods: PubMed was systematically searched for systematic reviews published between January 01, 2010, and December 06, 2017, that provided barriers to medication adherence. The searches were limited to reviews having adherence to medication prescribed in the outpatient setting as the main topic.Results: Thirty-one reviews were included in this review, covering 13 different disease categories. Fifty-eight different barriers to adherence to medications for chronic conditions were identified. Nineteen barriers were cited 6 or more times, and these were further categorized based on the World Health Organization’s 5 dimensions of adherence and the number of times cited.Conclusion: This review provides clear evidence that adherence to medication is affected by multiple barriers. To facilitate this, adherence barriers can be framed as physician/health system hurdles. With that focus in mind, we may put the responsibility where we have the most control. Keywords: medication adherence, patient compliance, medication non-compliance, patient acceptance of health care

Nupur U Patel,1 Kayla Felix,1 Danielle Reimer,1 Steven R Feldman1–3 1Center for Dermatology Research, Department of Dermatology, 2Department of Pathology, 3Department of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA Abstract: While topical medications remain the cornerstone of the psoriasis treatment paradigm, they also come with the risk of multiple side effects. An alternative topical treatment option, calcipotriene or calcipotriol, is a vitamin D derivative that is thought to work by inhibiting keratinocyte proliferation and enhancing keratinocyte differentiation. Multiple studies have demonstrated its efficacy and safety in improving psoriasis when used in combination with topical corticosteroids. Given the effectiveness and side effect profile seen with this combination of topical steroid and calcipotriene, the US Food and Drug Administration approved a calcipotriene/betamethasone dipropionate product for use in psoriasis patients over the age of 12 in 2006. Our paper seeks to review clinical trial evidence of this combination medication and its use in the treatment of psoriasis vulgaris. While assessment of available evidence indicates that the topical medication is both safe and effective for the treatment of psoriasis vulgaris, addressing limitations of what is known, such as tolerability, adherence, and patient preference, of this combination drug in future high-impact studies is needed. Keywords: calcipotriene, betamethasone diproprionate, psoriasis, topical treatment, steroids, vitamin D

Michael S Anderson,1 Anish Nadkarni,1 Leah A Cardwell,1 Hossein Alinia,1 Steven R Feldman1–3 1Department of Dermatology, Center for Dermatology Research, 2Department of Pathology, 3Department of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA Background: Brimonidine tartrate is a highly selective alpha 2 agonist that induces direct vasoconstriction of small arteries and veins, thereby reducing vasodilation and edema. Objective: To review the current literature regarding the safety, efficacy, and patient acceptability of brimonidine 0.33% gel.Methods: A PubMed search was performed using the terms brimonidine 0.33% gel, rosacea, safety, efficacy, and acceptability. Peer-reviewed clinical trials and case reports from 2012 to 2016 were screened for inclusion of safety, efficacy, and/or patient acceptability data.Results: Brimonidine topical gel 0.33% is associated with mild, transient skin-related adverse reactions. Efficacy may be achieved within 30 minutes of administration with maximal reductions in erythema 3–6 hours after administration. Patient satisfaction with use of brimonidine topical gel is superior to vehicle gel for facial appearance, treatment effect, facial redness, and daily control of facial redness.Limitations: Studies were typically limited to 1-year follow-up. Only one study has examined the use of brimonidine topical gel in combination with other rosacea and acne medications.Discussion: Brimonidine topical gel 0.33% is a safe, effective, and patient-accepted treatment for facial erythema of rosacea. Keywords: patient satisfaction, adverse reactions, side effects

Elias Oussedik,1 Capri G Foy,2 E J Masicampo,3 Lara K Kammrath,3 Robert E Anderson,1 Steven R Feldman1,4,5 1Center for Dermatology Research, Department of Dermatology, Wake Forest School of Medicine, Winston-Salem, NC, USA; 2Department of Social Sciences and Health Policy, Wake Forest School of Medicine, Winston-Salem, NC, USA; 3Department of Psychology, Wake Forest University, Winston-Salem, NC, USA; 4Department of Pathology, Wake Forest School of Medicine, Winston-Salem, NC, USA; 5Department of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA Abstract: Piano lessons, weekly laboratory meetings, and visits to health care providers have in common an accountability that encourages people to follow a specified course of action. The accountability inherent in the social interaction between a patient and a health care provider affects patients’ motivation to adhere to treatment. Nevertheless, accountability is a concept not found in adherence models, and is rarely employed in typical medical practice, where patients may be prescribed a treatment and not seen again until a return appointment 8–12 weeks later. The purpose of this paper is to describe the concept of accountability and to incorporate accountability into an existing adherence model framework. Based on the Self-Determination Theory, accountability can be considered in a spectrum from a paternalistic use of duress to comply with instructions (controlled accountability) to patients’ autonomous internal desire to please a respected health care provider (autonomous accountability), the latter expected to best enhance long-term adherence behavior. Existing adherence models were reviewed with a panel of experts, and an accountability construct was incorporated into a modified version of Bandura’s Social Cognitive Theory. Defining accountability and incorporating it into an adherence model will facilitate the development of measures of accountability as well as the testing and refinement of adherence interventions that make use of this critical determinant of human behavior. Keywords: autonomous accountability, controlled accountability, duress, health promotion, Self-Determination Theory, shame, Social Cognitive Theory, volition

Nupur U Patel,1 Blake A Moore,1 Rebekah F Craver,2 Steven R Feldman1,2 1Department of Dermatology, Center for Dermatology Research, 2Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, USA Abstract: Poor adherence to treatment is a common cause of medical treatment failure. Studying adherence is complicated by the potential for the study environment to impact adherence behavior. Studies performed without informing patients about adherence monitoring must balance the risks of deception against the potential benefits of the knowledge to be gained. Ethically monitoring a patient’s adherence to a treatment plan without full disclosure of the monitoring plan requires protecting the patient’s rights and upholding the fiduciary obligations of the investigator. Adherence monitoring can utilize different levels of deception varying from stealth monitoring, debriefing after the study while informing the subject that some information had been withheld in regard to the use of adherence monitoring (withholding), informed consent that discloses some form of adherence monitoring is being used and will be disclosed at the end of the study (authorized deception), and full disclosure. Different approaches offer different benefits and potential pitfalls. The approach used must balance the risk of nondisclosure against the potential for confounding the adherence monitoring data and the potential benefits that adherence monitoring data will have for the research subjects and/or other populations. This commentary aims to define various methods of adherence monitoring and to provide a discussion of the ethical considerations that accompany the use of each method and adherence monitoring in general as it is used in clinical research. Keywords: compliance, stealth monitoring, deception, adherence monitoring

Sara Moradi Tuchayi,1 Tiffany M Alexander,2 Anish Nadkarni,1 Steven R Feldman1,3,4 1Center for Dermatology Research, Department of Dermatology, Wake Forest University School of Medicine, Winston-Salem, NC, 2Howard University College of Medicine, Washington, DC, 3Department of Public Health Sciences, 4Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, NC, USA Background: Adherence to acne medication is poor and is a major reason why treatment plans are ineffective. Recognizing solutions to nonadherence is critical. Objective: The purpose of this study is to describe the hurdles associated with acne nonadherence and to provide mechanisms on how to ameliorate them. Methods: PubMed database was searched. Of the 419 search results, 29 articles were reviewed to identify hurdles to adherence and corresponding solutions. Results: Hurdles to primary nonadherence where the medication is not even started, include lack of knowledge, confusion about usage, weak physician–patient relationship, fear of adverse reactions, and cost. Secondary nonadherence hurdles where the medication is started but is not taken as directed include lack of results, complex regimens, side effects, busy lifestyle, forgetfulness, inconvenience, and psychiatric comorbidity. Solutions to these hurdles include treatment simplification, technology, and dynamic education. Limitations: Adherence is affected by numerous factors, but available literature analyzing acne adherence and interventions to improve adherence to treatment is limited. Conclusion: There are several hurdles in adhering to acne treatment. Recognition of these hurdles and finding appropriate solutions may be as important to treatment outcomes as choosing the right medication to prescribe. Keywords: acne vulgaris, adherence, pathogenesis, treatment, quality of life, prevalence, physician–patient relationship, lifestyle, clinic visit, disease severity

Leah A Cardwell,1 Hossein Alinia,1 Sara Moradi Tuchayi,1 Steven R Feldman,1–31Department of Dermatology, Center for Dermatology Research, 2Department of Pathology, 3Department of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA Abstract: Rosacea is a chronic dermatological disorder with a variety of clinical manifestations localized largely to the central face. The unclear etiology of rosacea fosters therapeutic difficulty; however, subtle clinical improvement with pharmacologic treatments of various drug categories suggests a multifactorial etiology of the disease. Factors that may contribute to disease pathogenesis include immune abnormality, vascular abnormality, neurogenic dysregulation, presence of cutaneous microorganisms, UV damage, and skin barrier dysfunction. The role of ivermectin in the treatment of rosacea may be as an anti-inflammatory and anti-parasitic agent targeting Demodex mites. In comparing topical ivermectin and metronidazole, ivermectin was more effective; this treatment modality boasted more improved quality of life, reduced lesion counts, and more favorable participant and physician assessment of disease severity. Patients who received ivermectin 1% cream had an acceptable safety profile. Ivermectin is efficacious in decreasing inflammatory lesion counts and erythema. Keywords: papulopustular rosacea, topical ivermectin, metronidazole, azelaic acid, topical

Sree S Kolli,1 Wasim Haidari,1 Steven R Feldman1–31Center for Dermatology Research, Department of Dermatology, Wake Forest School of Medicine, Winston-Salem, NC, USA; 2Department of Pathology, Wake Forest School of Medicine, Winston-Salem, NC, USA; 3Department of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA Kowalski et al describe various treatment approaches to achieve better outcomes in treatment-resistant prurigo nodularis in an article entitled, “Treatment-resistant prurigo nodularis: challenges and solutions.”1 Many excellent approaches are suggested, but the issue of nonadherence to topical therapies may be an overlooked issue commonly contributing to “treatment-resistance.” Often, in the face of “resistant” disease, patients may be prescribed more complicated or risky treatment regimens that make adherence even more difficult. Such strategies may not be the most effective ones when poor adherence underlies seemingly treatment-resistant prurigo nodularis.Treatment-resistance can often be overcome by measures that improve adherence. Even patients with severe, refractory atopic dermatitis respond rapidly to midpotency topical corticosteroids applied in the inpatient setting. Prurigo nodularis is often secondary to atopic dermatitis and psoriasis. In patients with atopic dermatitis or psoriasis that was “resistant” to topical corticosteroids, all patients treated with an easy to use topical corticosteroid spray improved rapidly when coupled with adherence promoting measures (telephone reminders, patient education and frequent office visits). Adherence to topical treatments is bad in the short-term and abysmal in the long-term.2–4 Perhaps one of the best approaches when faced with treatment-resistant disease is to simplify the treatment regimen and encourage good use of treatment, or better yet, bring patients in to assure the treatment is administered. View the original paper by Kowalski and colleagues

Alexandria M Bass,1 Michael E Farhangian,1 Steven R Feldman1–3 1Center for Dermatology Research, Department of Dermatology, Wake Forest School of Medicine, Winston-Salem, NC, USA; 2Department of Pathology, Wake Forest School of Medicine, Winston-Salem, NC, USA; 3Department of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA Background: Treatment adherence is a ubiquitous challenge in medicine, particularly in the adolescent population with chronic disorders. Web-based adherence interventions may be particularly useful in adolescents, due to their familiarity with and frequent use of the Internet. Objective: To review web-based interventions used to improve adherence to medication in adolescent patients with chronic disorders. Methods: A PubMed search was performed for full-text, English, clinical trials in adolescents using keywords “adherence” or “compliance”, “Internet” or “web”, and “treatment” from inception until November 2014. Articles were selected if they involved using the Internet to provide support to adolescents to help improve their adherence to treatment, excluding those focused on solely providing medical services through the Internet and articles focusing on preventative care, rather than treatment of an illness. Results: Fourteen studies were found concentrating on chronic adolescent disorders. Interventions included online surveys, physician chat lines, monitoring programs, and interactive programs. All interventions experienced either greater improvement in adherence or another disease control measure or no statistically significant difference compared with the control group (in-clinic visits). Limitations: Few clinical trials studying web-based interventions to improve adherence in adolescents were found. Due to not having one standard outcome measured in all of the studies, it was also difficult comparing the effectiveness of the interventions. Conclusion: Web-based interventions play a role in improving adherence in adolescents with chronic disorders by being more time saving and cost effective compared with in-clinic visits. Further research focusing on adherence interventions using the Internet is necessary to determine the ideal ways of utilizing the Internet to improve adherence in adolescents with chronic disorders. Keywords: web, compliance, teenagers, acne, diabetes, pediatrics

Laura F Sandoval,1 Brooke Williams,1 Steven R Feldman1–3 1Department of Dermatology, Center for Dermatology Research, Wake Forest School of Medicine, Winston-Salem, NC, USA; 2Department of Pathology, Wake Forest School of Medicine, Winston-Salem, NC, USA; 3Department of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA Abstract: Brodalumab is an anti-IL-17 receptor monoclonal antibody currently in development for the treatment of moderate-to-severe plaque psoriasis. With many systemic psoriasis therapies to choose from, and several newer agents in development, physicians need up to date evidence for the use of these drugs. A PubMed search was conducted through August 1, 2014 to identify randomized controlled trials and systematic reviews of brodalumab for the treatment of psoriasis. Results of Phase I and II trials, as well as a few smaller studies, have provided promising data on efficacy, safety, health-related quality of life, pharmacokinetics, and changes in lesional skin. Early Phase III data continue to support the use of brodalumab as a potentially valuable option for the treatment of psoriasis. Keywords: anti-interleukin-17, psoriasis, biologic agents, efficacy, safety, systemic therapy

Arash Taheri,1 Laura F Sandoval,1 Sara Moradi Tuchayi,1 Hossein Alinia,1 Parisa Mansoori,2 Steven R Feldman1–3 1Center for Dermatology Research, Department of Dermatology, 2Department of Pathology, 3Department of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA Abstract: The treatment of psoriasis has evolved over the years, with the recent focus largely on the use of biologics and anti-interleukin-17 agents. With treatment options expanding, practitioners and patients may find control of psoriasis more convenient and safer to achieve. In this article, we review the literature on emerging medications for the treatment of psoriasis. Although some of the new medications under development, such as the anti-interleukin-17 agents, are being shown to be very efficacious in the treatment of psoriasis in premarketing trials, more information regarding their long-term use is needed to demonstrate their superiority over available modalities. Keywords: psoriasis, therapy, interleukin-17, biologics, emerging, treatment

Swetha Narahari Pathak,1 Pauline L Scott,1 Cameron West,1 Steven R Feldman,1–3 1Center for Dermatology Research, Departments of Dermatology, 2Center for Dermatology Research, Departments of Pathology, 3Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA Abstract: Psoriasis is a chronic inflammatory disorder effecting the skin and joints. Additionally, multiple comorbidities exist, including cardiovascular, metabolic, and psychiatric. The chronic nature of psoriasis is often frustrating for both patients and physicians alike. Many options for treatment exist, though successful disease management rests largely on patients through the application of topical corticosteroids, Vitamin D analogs, and calcineurin inhibitors, amongst others and the administration of systemic medications such as biologics and methotrexate. Phototherapy is another option that also requires active participation from the patient. Many barriers to effective self-management of psoriasis exist. Successful treatment requires the establishment of a strong doctor-patient relationship and patient empowerment in order to maximize adherence to a treatment regimen and improve outcomes. Improving patient adherence to treatment is necessary in effective self-management. Many tools exist to educate and empower patients, including online sources such as the National Psoriasis Foundation and online support group, Talk Psoriasis, amongst others. Effective self management is critical in decreasing the physical burden of psoriasis and mitigating its multiple physical, psychological, and social comorbidities, which include obesity, cardiovascular disease, alcohol dependence, depression, anxiety, and social anxiety. Keywords: psoriasis, adherence, self management, compliance

Jonisha Shepherd,1 Arash Taheri,1 Steven R Feldman1–31Center for Dermatology Research, Department of Dermatology, 2Department of Pathology, 3Department of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USABackground: Topical treatments are usually effective in mild psoriasis. However, the complexity of their use may result in low patient adherence with treatment. Combination of a vitamin D analog and a corticosteroid into a two-compound topical formulation has increased efficacy compared with either drug administered alone. Once-daily application of such a product would likely improve adherence. The purpose of this study was to determine whether twice-daily application of a calcipotriene + betamethasone topical formulation can provide improved clinical outcomes compared with once-daily treatment with the same product.Methods: A review of the literature was performed seeking clinical trials comparing once-daily versus twice-daily application of calcipotriene + betamethasone topical formulations for the treatment of psoriasis.Results: We found only one relevant clinical trial. This study showed similar efficacy and safety with once-daily versus twice-daily application of a topical calcipotriene + betamethasone formulation in the treatment of psoriasis vulgaris.Conclusion: Once-daily application of a topical calcipotriene + betamethasone formulation may offer increased patient convenience and potentially increased patient adherence with long-term treatment, compared with twice-daily use, without reducing the efficacy. In order to enhance adherence, patient preference regarding frequency of application of topical treatments should be considered when prescribing medications.Keywords: calcipotriene, betamethasone, once daily, twice daily, psoriasis, combination product

Xi Tan1, Steven R Feldman2, Rajesh Balkrishnan11Department of Clinical, Social and Administrative Sciences, College of Pharmacy, University of Michigan, Ann Arbor, MI, USA; 2Department of Dermatology, Wake Forest University School of Medicine, Winston-Salem, NC, USAAbstract: Psoriasis is a chronic immunologic disease characterized by red papules and plaques with a silver colored scale. The impact of psoriasis on patients’ overall quality of life is significant, broad, and deep, including effects on emotional wellbeing, psychological stress, self-esteem, relationship, work, social activities, financial burden, and even physical function. Although there are various measures available for assessing health-related quality of life (HRQoL) in research studies, there is no consensus on which measure is best to use in clinical practice or for research comparing different treatments. Choosing treatments based on patients’ specific individual preferences, goal-orientation, and close, attentive cooperation between patients and their doctors may be an effective strategy that can be applied to improve patients’ quality of life.Keywords: treatment, health related quality of life, HRQoL

Sarah D Fenerty1, Cameron West1, Scott A Davis1, Sebastian G Kaplan3, Steven R Feldman1,2,41Center for Dermatology Research, Department of Dermatology, 2Department of Pathology, 3Department of Psychiatry and Behavioral Medicine, 4Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USABackground: Patient adherence is an important component of the treatment of chronic disease. An understanding of patient adherence and its modulating factors is necessary to correctly interpret treatment efficacy and barriers to therapeutic success.Purpose: This meta-analysis aims to systematically review published randomized controlled trials of reminder interventions to assist patient adherence to prescribed medications.Methods: A Medline search was performed for randomized controlled trials published between 1968 and June 2011, which studied the effect of reminder-based interventions on adherence to self-administered daily medications.Results: Eleven published randomized controlled trials were found between 1999 and 2009 which measured adherence to a daily medication in a group receiving reminder interventions compared to controls receiving no reminders. Medication adherence was measured as the number of doses taken compared to the number prescribed within a set period of time. Meta-analysis showed a statistically significant increase in adherence in groups receiving a reminder intervention compared to controls (66.61% versus 54.71%, 95% CI for mean: 0.8% to 22.4%). Self-reported and electronically monitored adherence rates did not significantly differ (68.04% versus 63.67%, P = 1.0). Eight of eleven studies showed a statistically significant increase in adherence for at least one of the reminder group arms compared to the control groups receiving no reminder intervention.Limitations: The data are limited by imperfect measures of adherence due to variability in data collection methods. It is also likely that concomitant educational efforts in the study populations, such as instructions regarding proper administration and importance of correct dosing schedules, contributed to improved patient adherence, both in reminder and control arms. The search strategy could have missed relevant studies which were categorized by disease rather than adherence.Conclusions: Reminder-based interventions may improve adherence to daily medications. However, the interventions used in these studies, which included reminder phone calls, text messages, pagers, interactive voice response systems, videotelephone calls, and programmed electronic audiovisual reminder devices, are impractical for widespread implementation, and their efficacy may be optimized when combined with alternative adherence-modifying strategies. More practical reminder-based interventions should be assessed to determine their value in improving patient adherence and treatment outcomes.Keywords: patient adherence, medication reminders, treatment compliance

Ashley N Feneran1, William S Kaufman2, Tushar S Dabade1, Steven R Feldman1,3,41Department of Dermatology, Center for Dermatology Research, Wake Forest University School of Medicine, Winston-Salem, NC, USA; 2Medical College of Virginia, Richmond, VA, USA; 3Department of Pathology, Center for Dermatology Research, Wake Forest University School of Medicine, Winston-Salem, NC, USA; 4Department of Public Health Sciences, Center for Dermatology Research, Wake Forest University School of Medicine, Winston-Salem, NC, USABackground: Acne vulgaris is a chronic disease with several pathogenic factors. Multiple medications are typically used that can lead to nonadherence and treatment failure. Combination medications target multiple pathways of acne formation and may offer therapeutic benefit.Purpose: To explore the efficacy and tolerability of combination retinoid plus antimicrobial treatments in acne vulgaris.Methods: A PubMed and Google search was conducted for combination therapies of clindamycin and tretinoin, with secondary analysis of related citations and references. Similar searches were completed for the combination medications of benzoyl peroxide plus clindamycin or erythromycin, and for the combination therapy of adapalene and benzoyl peroxide.Results: Combination clindamycin phosphate and tretinoin gel was found to be more efficacious than monotherapy of either drug or its vehicle for acne, including inflammatory acne, and has a greater onset of action than either drug alone. Clindamycin phosphate and tretinoin gel was well-tolerated, and adherence to its use exceeded that of using both medications in separate formulations. Benzoyl peroxide-containing combination medications with clindamycin or erythromycin were both more effective in the treatment of acne than either drug alone. Both medications were well-tolerated, with dry skin being the most common adverse effect.Conclusions: Combination medications have superior efficacy and adherence, and have a similar tolerability profile compared with monotherapy of its components. Several studies have found antibiotic-containing combination products with a retinoid effective for acne. The use of antibiotic-containing combination medications for acne can lead to bacterial resistance. Due to this potential for bacterial resistance, benzoyl peroxide treatments are also recommended in combination with a retinoid.Keywords: erythromycin, adherence, efficacy, safety, tolerability

Pyoderma gangrenosum is a rare autoinflammatory skin disease. Treatment is multifactorial, addressing inflammation, pain, underlying disease, if present, and the wound. Gentian violet has been used for hundreds of years in a variety of dermatologic conditions for its anti-inflammatory properties. This study aims to evaluate gentian violet in wound healing for pyoderma gangrenosum. We conducted a retrospective chart review of patients with pyoderma gangrenosum treated with gentian violet at the Wake Forest School of Medicine Department of Dermatology in the last 10 years. The primary outcome was clinical improvement. Of the 34 cases that met inclusion criteria, 70% improved with gentian violet, 24% had no documented change, 3% initially improved then worsened, and 3% had unclear results. Gentian violet is a safe and cheap treatment that may improve resolution of pyoderma gangrenosum lesions in addition to systemic therapy.