Emerging systemic therapies for atopic dermatitis: biologics.

BACKGROUND: The mainstay of atopic dermatitis treatment has been largely unchanged over the last few decades. With improved understanding of the immunologic pathways underlying atopic dermatitis in recent years, targeted biologic therapies are being developed. OBJECTIVE: Discuss efficacy and safety profiles of emerging biologics in phase 2 and 3 clinical trials. METHODS: A systemic literature review was conducted to identify results of randomized, placebo-controlled trials of monoclonal antibodies up to March 1, 2020 for the treatment of atopic dermatitis. RESULTS: Targeted biologics appear to have acceptable safety profiles. Dupilumab, lebrikizumab, and nemolizumab demonstrate efficacy as agents producing improvement in clinical severity and pruritus. CONCLUSIONS: The growing class of biologics shows promise in meeting the needs of treatment-resistant atopic dermatitis. The use of validated core measurements is necessary for future trials in order to adequately compare agents and progress evidence-based medicine.

An assessment of current practices in the treatment of hidradenitis suppurativa: the rise of biologic therapy.

INTRODUCTION: Treatments for hidradenitis suppurativa (HS) have changed in the last decade. In this context, we studied how management practices have shifted. METHODS: We analyzed the National Ambulatory Medical Care Survey (NAMCS) from 2010 to 2016 to assess current treatment practices for HS. RESULTS: There were 1.78 (95% confidence interval 1.35, 2.22) million visits. Antibiotics were observed at 55.7% of visits and observations remained stable over time (p = .9, odds ratio 0.99 [0.73, 1.3]). Pain medications were observed at 15.5% of visits and observations remained stable over time (p = .4, odds ratio [0.87 [0.61, 1.2]). Biologic agents were observed at 0.9% of visits and observations remained stable over time (p = .4, odds ratio 0.61 [0.21, 1.7]). Systemic immunomodulators were observed at 2.6% of visits and observations remained stable over time (p = .08, odds ratio 0.42 [0.12, 1.1]). 100% of biologic agents and 88% of systemic immunomodulators were prescribed by dermatologists. DISCUSSION: The use of biologic agents did not increase in this interval, but it is higher than in an earlier assessment of the NAMCS. Nearly all systemic immunomodulators are prescribed by dermatologists. The ambulatory uptake of these agents did not alter the use of other treatment modalities within this timeframe.

Emerging systemic therapies for atopic dermatitis: oral small molecules and targeted topical agents.

BACKGROUND: Until recently, treatment of atopic dermatitis has been limited to topical corticosteroids, calcineurin inhibitors, phototherapy, and systemic immunomodulatory agents. With improved understanding of the pathogenesis underlying atopic dermatitis, targeted oral small molecules and topical agents are being developed. OBJECTIVE: Discuss efficacy and safety profiles of emerging oral small molecules and targeted topical agents in phase 2 and 3 clinical trials. METHODS: A systemic literature review was conducted to identify results of randomized, placebo-controlled trials of oral small molecules and topical Janus kinase inhibitors up to March 1 2020 for the treatment of atopic dermatitis. RESULTS: Three novel oral small molecules, abrocitinib, upadacitinib, and baricitinib, demonstrated improvement of clinical severity, pruritus, and quality of life with acceptable safety profiles. Apremilast, a phosphodiesterase inhibitor, was less efficacious with use limited by adverse effects. Two novel topical agents, ruxolitinib and delgocitinib, were effective and well-tolerated. CONCLUSIONS: Targeted therapeutics including oral small molecules and topical agents show promise for the treatment of atopic dermatitis. The use of validated core measures is necessary for future trials in order to adequately compare agents and progress evidence-based medicine.

Adverse Medical Conditions Across Treatment Options in Patients With Psoriasis: A Claims-Based Analysis

Objective: To assess the real-world risk of developing adverse medical conditions (AMCs) among patients with psoriasis treated with biologic therapies or conventional systemic/topical therapies (CST/topical). Methods: Adult patients with psoriasis were identified from the Truven MarketScan US claims database (2008 Q3­2015 Q3) and classified into cohorts based on treatment initiated on the index date (adalimumab [ADA], etanercept [ETN], ustekinumab [UST], infliximab [IFX], or CST/topical). Incident AMCs were identified while on treatment from diagnoses recorded in medical claims and included abnormal test results, infections, mental disorders, cardiovascular disease, malignancies (skin and non-skin), and respiratory disease. Cox proportional hazards models were used to compare AMC risk for (1) ADA, ETN, and UST (separately) vs CST/topical, and (2) ADA vs other biologic therapies (ETN, UST, and IFX combined). Regressions were adjusted for age, gender, region, insurance plan type, year, Charlson comorbidity index, and prior AMCs; and based on stepwise selection, comorbidities, specialist encounters, and frequently prescribed treatments. Results: A total of 42,981 patients were identified (ADA: 5,197; ETN: 3,311; UST: 1,370; IFX: 187; CST/topical: 32,916). Across cohorts, median age was 46­50 years, 46.2%­53.1% were female, and median follow-up duration was 3.3­7.9 months. For all cohorts, infection was the most frequent AMC (28.7%­41.8%). Compared with CST/topical, ADA, ETN, and UST were associated with a lower risk of infections (adjusted hazard ratio [aHR]: 0.93, 0.92, and 0.86, respectively, all P<0.05). ADA was associated with a lower risk of malignancies (aHR: 0.71, P<0.05), and ETN was associated with a lower risk of respiratory disease (aHR: 0.80, P<0.05). Compared with biologic therapies, ADA was not associated with higher risk of AMCs. Conclusions: Compared to CST/topical, biologic therapies were associated with similar or lower risk of AMCs. Comparison between ADA and other biologic therapies suggests a similar safety profile with respect to the studied AMCs.

Trends in systemic psoriasis treatment therapies from 1993 through 2010.

BACKGROUND: Moderate-to-severe psoriasis generally requires systemic therapy, and is often undertreated. OBJECTIVE: To determine and analyze what courses of treatment and in what frequency are being utilized to combat psoriasis in the United States. METHODS: Analysis of data from the National Ambulatory Medical Care Survey (NAMCS) and National Hospital Ambulatory Medical Care Survey (NHAMCS) of the National Center for Health Statistics. Data were analyzed to examine the prevalence of different therapy techniques to combat psoriasis from 1993 through 2010. The trends for phototherapy, methotrexate (MTX), retinoids, cyclosporine A (CSA), systemic steroids, and biologics were all analyzed over the entire 18-year period and independently before and after the introduction of biologics in 2002. RESULTS: From 1993 to 2010, the trend for total systemic treatments has not significantly increased (P=0.5). Frequency of phototherapy treatments significantly decreased from 1993 to 2010 (P<0.001). Since the introduction of biologics in 2002, their frequency has significantly increased, becoming the most frequently used treatment from 2008-2010 (P<0.0001). LIMITATIONS: Severity of psoriasis was not recorded in the NAMCS and NHAMCS. CONCLUSIONS: The frequency of systemic treatments to treat psoriasis has not significantly increased from 1993 to 2010. Despite the introduction of biologics, it appears that little progress has been made in reducing under-treatment of moderate-to-severe psoriasis.

An over-the-counter moisturizer is as clinically effective as, and more cost-effective than, prescription barrier creams in the treatment of children with mild-to-moderate atopic dermatitis: a randomized, controlled trial.

BACKGROUND: Atopic dermatitis (AD) is a prevalent skin disorder with significant cost of treatment. Several prescription device moisturizers have been approved by the FDA to treat AD but are significantly more expensive than well-crafted over-the-counter (OTC) moisturizers. No studies have been performed to compare both the clinical efficacy and cost-efficacy of these prescription devices to OTC moisturizers. PURPOSE: The purpose of this study is to compare the clinical efficacy and cost-efficacy of a glycyrrhetinic acid-containing barrier repair cream (BRC-Gly, Atopiclair®), a ceramide-dominant barrier repair cream (BRC-Cer, EpiCeram®) and an OTC petroleum-based skin protectant moisturizer (OTC-Pet, Aquaphor Healing Ointment®) as monotherapy for mild-to-moderate AD in children. METHODS: Thirty-nine patients, age 2-17 years, with mild-to-moderate AD were randomized 1:1:1 to receive one of three treatments-BRC-Gly, BRC-Cer or OTC-Pet-with instructions to apply the treatment three times daily for three weeks. Disease severity and improvement was assessed at baseline and on days 7 and 21. RESULTS: No statistically significant difference for any efficacy assessment was found between the three groups at each time point. The OTC-Pet was found to be at least 47 times more cost-effective than BRC-Gly or BRC-Cer. LIMITATIONS: The relatively small sample size of 39 subjects was not sufficient to establish OTC-Pet as superior treatment in AD. CONCLUSIONS: OTC-Pet is as effective in treating mild-to-moderate AD as both BRC-Gly and BRC-Cer and is at least 47 times more cost-effective. NAME OF REGISTRY: II-AF-ATD-Aquaphor, Comparing the Efficacy and Cost-Effectiveness of Aquaphor to Atopiclair and EpiCeram in Children with Mild to Moderate Atopic Dermatitis. REGISTRATION IDENTIFIER: NCT01093469.

Health care utilization among migrant Latino farmworkers: the case of skin disease.

CONTEXT: Skin diseases are common occupational illnesses for migrant farmworkers. Farmworkers face many barriers in accessing health care resources. PURPOSE: Framed by the Health Behavior Model, the purpose of this study was to assess health care utilization for skin disease by migrant Latino farmworkers. METHODS: Three hundred and four migrant and seasonal Latino farmworkers in North Carolina were enrolled in a longitudinal study of skin disease and health care utilization over a single agricultural season. Self-reported and dermatologist-diagnosed skin condition data were collected at baseline and at up to 4 follow-up assessments. Medical visit rates were compared to national norms. FINDINGS: Self-reported skin problems and diagnosed skin disease were common among farmworkers. However, only 34 health care visits were reported across the entire agricultural season, and none of the visits were for skin diseases. Nevertheless, self-treatment for skin conditions was common, including use of non-prescription preparations (63%), prescription products (9%), and home remedies (6%). General medical office visits were reported in 3.2% of the assessments, corresponding to 1.6 office visits per person year. CONCLUSIONS: The migrant farmworker population consists largely of young men who make little use of clinic services. Skin conditions are very common among these workers, but use of medical services for these conditions is not common. Instead, farmworkers rely primarily on self-treatment. Clinic-based studies of farmworker skin conditions will not account for most injury or disease in this population and have the potential for biased estimates.

Adherence to acitretin and home narrowband ultraviolet B phototherapy in patients with psoriasis.

BACKGROUND: In the treatment of psoriasis, patient adherence to oral medications is poor and even worse for topical therapy. However, few data exist about adherence rates to home phototherapy, adding to concerns about the appropriateness of home phototherapy as a psoriasis treatment option. OBJECTIVE: We sought to assess adherence to both oral acitretin and home ultraviolet B phototherapy for the treatment of psoriasis. METHODS: In all, 27 patients with moderate to severe psoriasis were treated with 10 to 25 mg of acitretin daily, combined with narrowband ultraviolet B, 3 times weekly at home, for 12 weeks. Adherence to acitretin was monitored by an electronic monitoring medication bottle cap, and to phototherapy by a light-sensing data logger. RESULTS: Adherence data were collected on 22 patients for acitretin and 16 patients for adherence to ultraviolet B. Mean adherence to acitretin decreased steadily during the 12-week trial (slope -0.24), whereas mean adherence to home phototherapy remained steady at 2 to 3 d/wk. Adherence was similar between patients who reported side effects and those who did not. LIMITATIONS: Small sample size and lack of follow-up on some patients were limitations of this study. CONCLUSIONS: Adherence rates to home phototherapy were very good and higher than adherence rates for the oral medication. Side effects of treatment were well tolerated in this small group and did not affect use of the treatment. Home phototherapy with acitretin may be an appropriate option for some patients with extensive psoriasis.

Self-treatment with bleach by a Latino farmworker.

Skin disease is common among migrant Latino farmworkers. These workers rarely use formal health care services but commonly engage in self-treatment of their skin disease. We present a patient with dermatitis who self-treated with bleach. This patient illustrates a common practice that exacerbates skin disease and sheds light on social and cultural factors of which health care providers serving this community should be aware.

Adverse events from systemic therapies for psoriasis are common in clinical practice.

BACKGROUND: Patients with moderate-to-severe psoriasis frequently require systemic treatment and these medications may be associated with adverse effects. Little is known about the frequency of these events when systemic agents are used in true clinical practice. OBJECTIVE: To determine the frequency of adverse events associated with various systemic psoriasis therapies. METHODS: A retrospective chart review of 753 patients treated in an academic dermatology practice was performed to identify the frequency of adverse events. Poisson regression was used to estimate the odds of significant events for each systemic therapy; UVB-treated patients served as a control population. RESULTS: Methotrexate seemed to be the most prescribed medication. Adverse events were noted with all forms of systemic psoriasis therapy. The highest event rate was seen with oral retinoids, though most of these were considered minor (64%). Cyclosporine had the highest significant adverse event rate (0.9 events/patient). For 'significant' adverse events, oral agents had an adjusted odds ratio>6 compared to standard UVB therapy. The highest risk was for cyclosporine (OR = 20.3); however, the estimate was imprecise (95% confidence interval [4.3, 96.6]). CONCLUSIONS: Traditional psoriasis therapies are associated with significant adverse events in some patients despite toxicity-sparing approaches such as combination therapy. Clinicians need to be aware of screening for adverse events in order to best ensure the safety of their patients and to maximize the efficacy of a given agent. There is still a need for the development of safe and effective treatments for patients with moderate-to-severe psoriasis.

Would elimination of copayments for phototherapy decrease the cost of treating psoriasis with systemic biologics? A cost analysis.

Phototherapy is a proven treatment method for the treatment of psoriasis, yet is typically underutilized because of the frequency of physician visits and copayments required for each session (typically 2-5 treatments/wk). Injectable biologic therapies are effective but costly. The objective of this study was to explore how changes in copayment strategies for phototherapy may affect biologic usage. Published estimates of the cost of phototherapy and biologic treatment were used to determine the costs of these treatments to patients and insurers. With an estimated patient copayment of $30 per office visit and a pharmacy copayment of $50 per month, the $1,800 annual patient expense for phototherapy far exceeds the estimated out-of-pocket expenses for etanercept, alefacept, and efalizumab ($840, $405, and $780, respectively). The estimated annual costs to MCOs ranged from $3,008 for phototherapy, to $20,300 for etanercept. Copayments for phototherapy may be shifting patients toward biologic treatment, which is more convenient but more costly to managed care plans.

Inpatient management of severe psoriasis.

Historically, severe psoriasis frequently required inpatient hospitalization for several weeks to reduce symptoms and prevent morbidity and mortality, Despite declining hospitalization rates there remain patients who undergo severe, acute psoriasis exacerbations requiring inpatient care. The majority of the literature describes the treatment of psoriasis in the outpatient setting. We review the inherent differences between the inpatient and outpatient management of psoriasis along several dimensions and discuss an approach to the inpatient treatment of severe psoriasis based upon therapeutic rate of onset, efficacy, and safety. The inpatient setting benefits from and lends itself to use of rapid acting, highly effective agents. Given the acute nature of psoriasis inpatient episodes, the risks associated with long-term use of a treatment are far less important in inpatient setting treatment planning than they are in the outpatient setting.

Limited availability of psoriasis and phototherapy care: an analysis of advertisements.

Because the number of dermatologists remains stable, patients with medical dermatologic conditions such as psoriasis may find it increasingly difficult to access dermatological treatment. Measuring the competition in the marketing of dermatologic care may provide insight into the availability of dermatology services. The purpose of this study was to determine to what extent dermatologists are using the Yellow Pages to advertise to patients with psoriasis. We performed a quantitative and qualitative assessment of dermatologists' Yellow Pages advertisements in small cities and the ten largest metropolitan regions in the country. Per capita, more advertisements were found in smaller markets than larger markets and a higher percentage was descriptive rather than just a name, address and phone number. Cosmetic and surgical advertisements were more common than psoriasis ads in both markets. Cosmetic ads were more prevalent in larger markets. In all regions, psoriasis and psoriasis treatment ads were least common. These findings raise the concern that incentive structures in the United States healthcare system do not adequately support delivery of dermatologic care for psoriasis. Efforts to promote psoriasis care should be encouraged.

The cost of psoriasis therapies: considerations for therapy selection.

PURPOSE: The purpose of this article is to provide a review of the cost of psoriasis therapies from two sources as well as compare the average wholesale price (AWP), as listed in the 2003 Drug Topics Red Book to that of a popular Internet pharmacy. METHODS: Prices of therapies were obtained two ways: the AWP was recorded from the 2003 Drug Topics Red Book. A range and average price per gram (or mL) were calculated based on the smallest size or quantity available. In addition, a price comparison was made to values as they were reported online at drugstore.com. Monthly cost estimates were based on average systemic dosing and for topicals, 18 g/month (for 1% body surface area [BSA] involvement). RESULTS: The prices of psoriatic treatment medications vary considerably--from the relatively inexpensive topical corticosteroids to the more costly biologic therapies. In the category of corticosteroids, a trend was evident between the overall price per gram of each class and the potency of each class. Class I and VI corticosteroids had an average price per gram (or mL) of dollars 2.08 (dollars 37/month/1% BSA) and dollars 0.86 (dollars 15/month/1% BSA), respectively. Nonsteroidal topical treatments had an average price per gram (or mL) dollars 2.18 (dollars 39/month/1% BSA). Systemic therapies have a wide range of costs. The total monthly expense, based on estimated average dosing, was calculated for methotrexate, acitretin, and cyclosporine and were dollars 78.60, dollars 400.50, and dollars 735.00, respectively. Biologic therapies designed for continuous use cost roughly dollars 1,300/month. DISCUSSION: There are numerous treatment options for psoriasis with a wide range of costs. In addition to significant challenges from a scientific perspective, psoriasis treatment is further complicated by the cost of the numerous medications. Prices reported in the AWP were similar in many instances to those listed at an Internet pharmacy. Many considerations should go into therapy selection for psoriasis and a comprehensive approach that includes cost will likely provide the best patient care.

The frequent use of oral retinoids in combination with other treatments for psoriasis: a retrospective analysis.

BACKGROUND: Combination treatment in psoriasis may be common, logical, and appropriate, even if not well tested or well documented by clinical trials. While oral retinoids such as acitretin can be used as monotherapy, efficacy can be further augmented by combination use with other agents. Similarly, because of its safety profile, acitretin can be added in low doses to help patients who have not achieved adequate control with other psoriasis treatments. OBJECTIVE: The purpose of this study was to assess how oral retinoids are used in combination with other drugs to treat psoriasis. METHODS: We assessed the use of acitretin and other oral retinoids for the treatment of psoriasis using two sources of information: nationally representative survey data from the National Ambulatory Medical Care Survey (NAMCS) and local data obtained by chart review of 518 patients seen in a university dermatology clinic. RESULTS: In the NAMCS, oral retinoids were prescribed with other psoriasis medications at 71% of visits. In the chart review, combination use was even more frequent (96% of subjects were on combination treatment) and included combinations of acitretin with topicals, phototherapy, and other systemic treatments. Adverse events were reported in 53% of patients treated with acitretin, although none were severe. CONCLUSION: Use of acitretin in combination with many other psoriasis treatments is a common practice. Mucocutaneous side effects of oral retinoids are common but with appropriate dosing are generally mild.

Itch associated with skin disease: advances in pathophysiology and emerging therapies.

Itch, also known as pruritus, is the major symptom in skin diseases with a variety of etiologies and pathophysiologies. Significant progress has been achieved in understanding the pathophysiology of itch in the last 5 years. Neurophysiological experiments in humans and animals have revealed that itch is carried by specific C nerve fibers. Recent studies have demonstrated that peripheral mediators other than histamine are involved in induction of itch. Mast cell tryptase seems to be an important mediator in itch by its activation of proteinase activated receptor 2 in the sensory nerves. Opioids have central and peripheral itch producing activity. Neuropeptides, such as substance P, induce itch by their effect on mast cells. Based upon our improved understanding of the neurophysiology of itch a clinical classification of itch has been proposed. The classification highlights differences between peripheral pruritoceptive itch, neuropathic itch (itch related to damage to afferent nerve fibers) and neurogenic itch (itch originating in the central nervous system without any evidence of nerve damage). Emerging therapies based on these findings include topical vanilloid receptor antagonists, topical antihistamines, and topical arachidonic acid inhibitors, as well as inhibitors of non-histamine inflammatory mediators, immunomodulators and strontium salts. Systemic therapies include thalidomide, opioid antagonists, phototherapy with narrow band UVB and experimental treatments with cutaneous field stimulation and vagal nerve stimulation. With the new information it seems we will be able to better help our dermatologic patients who have itch, however we are not closer to identifying a single agent specifically targetable to this symptom.

Phototherapy utilization for psoriasis is declining in the United States.

Phototherapy is an established treatment modality for psoriasis. The use of phototherapy for psoriasis appears to be in decline in nonfederal and non-university-based settings. We used data from the National Ambulatory Medical Care Survey to estimate the number of visits for phototherapy and psoralen ultraviolet A-range (PUVA) light therapy from 1993 to 1998. There were 873,000 visits for UV light therapy in 1993-1994, 189,000 in 1995-1996, and 53,000 in 1997-1998 (P <.0001). There were 175,000 psoralen visits in 1993-1994, 61,000 in 1995-1996, and 25,000 in 1997-1998 (P =.0053). Similar decreases in phototherapy visits occurred in our university-based practice. The decline in phototherapy represents decreased utilization of a safe and effective treatment for psoriasis.