February 27, 2019

Only 1 patient who received lanadelumab 150 mg every 4 weeks reported a treatment-emergent adverse event.

SAN FRANCISCO — Patients with hereditary angioedema did not demonstrate higher cardiovascular risk when treated with lanadelumab compared with placebo, according to research presented at the American Academy of Allergy, Asthma & Immunology Annual Meeting 2019, held February 22-25, 2019, in San Francisco, California.

Researchers sought to examine the effect of lanadelumab in reducing active plasma kallikrein, an important enzyme in regulating blood pressure, in patients with type I or type II hereditary angioedema in an analysis of the phase 3 HELP study (ClinicalTrials.gov Identifier: NCT02586805)

The study sample included 125 patients with hereditary angioedema who were ≥12 years old and who had reported ≥1 hereditary angioedema attacks during a 4-week run-in period. During the course of 26 weeks, the participants received either lanadelumab (n=84) 300 mg every 2 weeks, 300 mg every 4 weeks, or 150 mg every 4 weeks, or placebo (n=41). The patients were not permitted to use angiotensin-converting enzyme inhibitors during the study.

Of the patients who received lanadelumab doses, 78 (92.8%) completed the study, and 35 (85.4%) patients who received placebo completed the study. Twelve (14.3%) patients in the lanadelumab groups had a history of hypertension at baseline vs 6 (14.6%) patients in the placebo group had a history of hypertension. Over 26 weeks, blood pressure remained stable in the lanadelumab group; however, diastolic blood pressure slightly decreased in the placebo group compared with the lanadelumab groups (–3.17 mm Hg vs 1.34 mm Hg; P =.002). Neither group reported increased use of anti-hypertensive medications nor did the investigators observe any significant electrocardiographic abnormalities. Only 1 patient who received lanadelumab 150mg every 4 weeks reported a treatment-emergent adverse event in which the patient’s blood pressure increased to 124/91 mm Hg.

The investigators suggested that lanadelumab used to treat patients with hereditary angioedema was not associated with an increased risk of hypertension or electrocardiographic abnormalities.

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Reference

Sexton DJ, Brown NJ, Lumry WR, et al.  Lanadelumab and cardiovascular risk: findings from the phase 3 HELP Study. Presented at: American Academy of Allergy, Asthma & Immunology Annual Meeting 2019; February 22-25, 2019; San Francisco, CA. Abstract 136.

February 27, 2019

Researchers conducted a review of various botulinum neurotoxin type A formulations.

IncobotulinumtoxinA offers an advantage over other botulinum neurotoxin type A (BoNT-A) formulations because it is less likely to induce an immune response when used clinically. A review of various BoNT products was conducted and results were published in the Journal of Drugs in Dermatology.

In 2017, aesthetic dermatologic applications of BoNT formulations, including for treatment of horizontal forehead lines, glabellar lines, and crow’s feet, were the most common nonsurgical cosmetic procedures performed in the United States, with high levels of patient satisfaction reported. Since the first BoNT-A product was approved by the US Food and Drug Administration in 1989, the number of formulations available worldwide has increased, with new approvals anticipated.

It is well known that BoNT is produced by Clostridium botulinum as part of a large protein complex. The unnecessary clostridial proteins do not play a role in clinical applications. Data have demonstrated that BoNT administration can elicit an immune response, leading to the production of neutralizing antibodies that can be related to treatment nonresponse or reduced efficacy. With repeated treatments needed to maintain effectiveness, clinicians must be aware of the potential for antibody development and thus select a BoNT with the lowest risk for immunogenicity.

IncobotulinumtoxinA is purified and manufactured precisely using advanced technology and good manufacturing practice. The unnecessary clostridial proteins are removed using stepwise chromatography to isolate the pure BoNT accurately without any unnecessary clostridial proteins, resulting in high specific activity and low immunogenicity. Clinical studies of incobotulinumtoxinA have shown that participants who had never previously received BoNT did not have neutralizing antibodies or secondary nonresponse to incobotulinumtoxinA therapy.

The investigators concluded that the unique and precise purification of incobotulinumtoxinA represents innovative advances in the BoNT manufacturing process. Currently, incobotulinumtoxinA is the only BoNT formulation in commercial markets across the world that was designed intentionally to contain only the required therapeutic BoNT component.

“The data reviewed here suggest incobotulinumtoxinA offers an advantage over other BoNT-A formulations due to its lower potential to provoke an immune response when used clinically,” the researchers concluded.

Disclosures: Dr Kerscher reports relationships with Galderma/Q-Med, Ipsen, and MErz Pharmaceuticals GmbG. Dr Trindade de Almeida reports relationships with Allergan, Galderma/Q-Med, Lupin, Mantecorp, Merz Pharmaceuticals, and Sinclair. Drs Maas and Frevert report relationships with Merz Pharmaceuticals GmbH.

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Reference

Kerscher M, Wanitphakdeedecha R, Trindada de Almeida AT, Mass C, Frevert J. IncobotulinumtoxinA: a highly purified and precisely manufactured botulinum neurotoxin type A. J Drugs Dermatol. 2019;18(1):52-57.

February 27, 2019

A C-section was associated with both milk allergy and gastroesophageal reflux disease.

SAN FRANCISCO — Gestational duration and Cesarean sections (C-section) were associated with comorbid atopic dermatitis and food allergies in children, respectively, according to research presented at the American Academy of Allergy, Asthma & Immunology Annual Meeting, held February 22-25, 2019, in San Francisco, California.

Researchers analyzed the link between gestational factors and delivery variables and food allergen profiles and food allergy-related comorbidities. Data on 195 children with food allergies were collected using questionnaires about demographics, duration of pregnancy, mode of delivery, age of food allergy onset, and types of food allergies.

A shorter duration of pregnancy was significantly associated with atopic dermatitis (P =.01). Children with atopic dermatitis had a mean gestational age of 37.5 weeks (SD±3.6 weeks) and children without atopic dermatitis had a mean gestational age of 38.2 weeks (SD±2.8 weeks). A C-section was associated with both milk allergy (P =.04) and gastroesophageal reflux disease (P =.001). In children with a milk allergy, 26.8% were delivered by C-section vs 19.6% without a milk allergy and, 25.4% of the children with gastroesophageal reflux disease were also delivered by C-section.

Further research is needed to determine whether gestational factors and delivery variables affect the food allergy profile and atopic dermatitis, or whether there is an underlying cause that affects gestation time and delivery mode as well as a predisposition to food allergies in these children.

The researchers concluded that “C-section was associated with milk allergy and [gastroesophageal reflux disease], while duration of pregnancy was linked to comorbid [atopic dermatitis].”

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Reference

Andy-Nweye AB, Jois SK, Jungles KN, Tobin MC, Mahdavinia M. Mode of delivery and duration of pregnancy is associated with allergy to milk and atopic dermatitis in children. Presented at: American Academy of Allergy, Asthma & Immunology Annual Meeting 2019; February 22-25, 2019; San Francisco, CA. Abstract 433.

February 26, 2019

Factors positively associated with MIR included dermatologist density, percent of the population that is non-Hispanic white, and average household income.

States with a higher count of total physicians per capita and a larger percentage of non-Hispanic whites have worse survival rates for melanoma, while more dermatologists per capita and more National Cancer Institute-designated Cancer Centers (NCIDCCs) appear to be correlated with improved melanoma survival, , according to a study published in Journal of the American Academy of Dermatology.

The current study was designed to evaluate possible healthcare-based and sociodemographic predictors of melanoma survival differences in the United States using the melanoma mortality-to-incidence ratio (MIR). United States Cancer Statistics data from 1999 to 2014 were used to calculate state-based MIRs, and linear regressions and Pearson correlations were used to identify associations between MIRs and primary care provider density, dermatologist density, number of physicians by state, healthcare spending per capita, percentage of uninsured, number of National Cancer Institute-designated Cancer Centers, racial/ethnic makeup of the population, average household income, and percentage with a bachelor’s degree.

The overall mean MIR was 0.15±0.04, with Alaska as an outlier at 0.24±0.03. MIR in most states decreased over time. Factors positively associated with MIR included dermatologist density (P <.001), percent of the population that is non-Hispanic white (P <.001), and average household income (P =.01). Factors that were negatively and significantly associated with MIR included primary care provider density (P =.001), number of physicians (P =.002), NCIDCCs per state (P =.02), healthcare spending per capita (P <.001), percent of population with a bachelor’s degree (P <.001), and percent of population that is Native Hawaiian/Other Islander (P <.001), Asian (P =.01), Native American/Native Alaskan (P =.01), and Black (P <.001). 

No significant associations were seen between the percentage of uninsured and MIR. Only the percentage of the population that is non-Hispanic white (P =.004) and the number of active physicians (P =.02) remained significantly associated with MIR after multivariable regression analysis. Significant Pearson correlations were found between MIR and melanoma incidence (r=0.72, P <.001), dermatologist density (r=0.32, P <.001), NCIDCC count (r=-0.12, P =.001), and melanoma mortality (r=0.38, P <.001).

Limitations included reporting difficulties and database inaccuracies, limited data on melanoma thickness and staging, census-based demographic data, and lack of insight into intra-state disparities.

Study investigators concluded that, “states with more physicians (i.e., higher total physician count, not just dermatologists) per capita and a larger percentage of non-Hispanic whites had higher MIRs, or worse survival. We also found that intrinsic differences between states accounts for the vast majority of variance in MIR, suggesting the need for local evaluation and policy changes.”

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Reference

Hopkins ZH, Moreno C, Carlisle R, Secrest AM. Melanoma prognosis in the United States: identifying barriers for improved care [published online January 16, 2019]. J Am Acad Dermatol. doi: 10.1016/j.jaad.2019.01.003

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February 25, 2019

Researchers conducted a post hoc analysis of 2 identical multicenter, randomized, double-blind, vehicle-controlled phase 3 clinical studies in moderate to severe acne.

A novel tretinoin 0.05% lotion formulation is an effective, safe, and well-tolerated topical treatment for moderate to severe comedonal and inflammatory acne in a population of Hispanic patients, with no reports of the product causing or exacerbating postinflammatory hyperpigmentation. Results of the post hoc analysis were published in the Journal of Drugs in Dermatology.

The novel tretinoin formulation evaluated in this analysis was developed with the use of a novel polymerized emulsion technology to provide a treatment option for Hispanic patients with acne who may be sensitive to some of the skin irritation, dryness, and pigmentary changes associated with the use of other tretinoin products. A total of 766 Hispanic participants 11 to 50 years old were randomly assigned in a 1:1 ratio to receive tretinoin 0.05% lotion or vehicle, applied once daily for 12 weeks.

Efficacy assessments included changes in baseline inflammatory and noninflammatory lesions, as well as treatment success, which was defined as a ≥2-grade reduction from baseline in Evaluator’s Global Severity Score and “clear” or “almost clear.” Adverse events (AEs), safety, and cutaneous tolerability were all evaluated with the use of a 4-point scale (0=none and 3=severe).

At week 12, the mean percentage changes from baseline in inflammatory and noninflammatory lesion counts were 60.1% and 53.0%, respectively, with tretinoin 0.05% lotion compared with 51.1% (P =.001) and 38.7% (P <.001) with vehicle, respectively. These reductions demonstrated statistical significance. Treatment success was attained among 19.6% of participants by week 12 compared with 12.7% of vehicle-treated patients (P =.015).

The majority of AEs were mild and transient in nature. Overall, 4 serious AEs were reported (2 in each treatment group), but none of the AEs was  related to the treatment. Moreover, the incidence of treatment-related AEs was lower with tretinoin 0.05% lotion compared with that in the overall study population. The most commonly reported treatment-related AEs included application-site pain (2.0%), dryness (1.4%), and erythema (1.2%). Local cutaneous safety and tolerability evaluations, which were mostly mild to moderate at baseline, improved at week 12. Slight transient increases in burning and scaling were observed over the first 4 weeks. The severity of hyperpigmentation was reduced progressively with treatment.

The investigators concluded that the novel tretinoin 0.05% lotion used in this study was effective, safe, and well tolerated by the participants. A longer-term study is warranted to provide additional insight into postinflammatory hyperpigmentation severity associated with this treatment in a Hispanic population.

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Reference

Cook-Bolden FE, Weinkle SH, Guenin E, Bhatt V. Novel tretinoin 0.05% lotion for once-daily treatment of moderate-to-severe acne vulgaris in a Hispanic population. J Drugs Dermatol. 2019;18(1):32-38.

February 25, 2019

Dermatologists have not traditionally played a systematic role in recommending and administering immunizations.

Widespread encouragement among dermatologists and other physicians to regularly recommend and/or offer the herpes zoster (HZ) vaccine to their patients is key to prevention of the disease.

Approved in 2017, the recombinant HZ vaccine (HZ/su) was designed to prevent HZ infection and associated sequelae with greater efficacy and safety than the zoster vaccine live (ZVL) precursor vaccine. A review and an update on the prevention of HZ infection, along with the current role played by dermatologists in fostering administration of the vaccine, was published in the Journal of Drugs in Dermatology.

Although dermatologists encounter patients with HZ infection regularly, recommendation of vaccination against the disease has been minimal over the past years, resulting in low rates of overall patient awareness and use of HZ vaccines. As the HZ/su vaccine has several improvements over the live vaccine, dermatologists nonetheless still encounter impediments to vaccine recommendation and administration, including concerns about efficacy, limited availability, and complex cost and reimbursement for vaccine administration. Moreover, dermatologists have not traditionally played a systematic role in recommending and administering immunizations.

The investigators conducted a review of the literature to study the current role played by dermatologists and other physicians in HZ prevention, the safety and efficacy of the HZ/su vaccine, potential barriers to its recommendation by dermatologists, and the practicality of administering HZ/su vaccines in dermatology offices. The primary search database used in the analysis was PubMed/Medline.

The HZ/su vaccine costs approximately $290 for 2 doses, which is more expensive than the ZVL vaccine which costs approximately $230. Although the vaccine is more expensive than the ZVL vaccine, because of the efficacy that has been demonstrated by the HZ/su vaccine in randomized controlled trials, the HZ/su vaccine has been deemed more cost-effective compared with the ZVL vaccine or nonimmunization according to the costs of HZ treatment and the management of possible sequelae.

The investigators concluded that dermatologists are in a prime position to make the HZ/su vaccine more available to their patients. If the HZ/su vaccine, or a means of receiving the vaccine, is offered regularly at dermatology appointments, not only will dermatologists become accustomed to recommending the vaccine, but patients will also be more likely to obtain the immunization at the time it is recommended. Additional options for increasing HZ vaccine use include educational training for healthcare providers, partnering with the manufacturers of the vaccine, partnering with pharmacies, and widespread patient education.

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Reference

Felix KA, Ediale CE, McMichael AJ. Update in herpes zoster prevention and the role of dermatologists. J Drugs Dermatol. 2019;18(1):18-22.

February 25, 2019

CeraVe products containing salicylic acid may significantly improve dry, flaky, or scaly skin conditions.

The daily use of a ceramide-containing cleanser and cream that also contains salicylic acid has been shown to improve skin conditions significantly in individuals with dry, flaking, and/or scaling skin. A cohort study of adults with mild to moderate dry skin conditions was conducted at 4 dermatology centers in Canada, with results published in the Journal of Drugs in Dermatology.

Between November 2017 and May 2018, a total of 35 adults (18 men, 17 women) with mild to moderate dry skin conditions were recruited to the multicenter cohort. Participants received treatment with CeraVe Hydrating Cleanser Bar (HCB) and CeraVe Renewing SA (CSA) cream. All participants were treated with the ceramide-containing cleanser and cream, which also contained salicylic acid. Ceramides are known to be key physiologic lipids required for construction and maintenance of the epidermal barrier of the skin.

The primary outcome of the study was the physician’s and participant’s evaluation of the participant’s skin condition by comparing baseline (day 0) with day 28±5 days using the Dry Skin Classification Scale and the Global Aesthetic Improvement Scale. Secondary study outcomes were participant satisfaction with use of the treatment regimen and product features using a 5-point Likert scale (1=strongly agree and 5=strongly disagree). Tolerability, safety, and quality-of-life aspects were also evaluated.

A total of 34 individuals completed the study, with 1 participant lost to follow-up. One body area (ie, torso, back or front, left or right arm, or left or right leg) could be chosen to be treated with the cleansing bar and CSA cream. The selection of body location was made by the participant in agreement with the physician who conducted the study. After cleansing using the bar, CSA cream was applied to the affected area twice-daily.

Daily use of the cleanser and CSA cream improved the skin condition significantly in participants with dry, flaking, and/or scaling skin when day 0 was compared with day 28. Per the ratings of both the physicians and the participants, significant improvements in skin condition were noted in the Dry Skin Classification Scale and the Global Aesthetic Improvement Scale (P <.05 for both). Moreover, participants indicated that the treatment improved their skin condition significantly by reducing the negative impact on their professional life, as well as on their self-image and social life (P <.05 for all). Use of the product proved to be safe, well tolerated, and comfortable.  

A major limitation of the current study that it presented a description of practice and did not include a comparator or control group. Thus, no cause and effect associations could be inferred. The investigators concluded that future studies are warranted to draw any conclusions about the evaluated products on possible underlying disease among the participants.

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Reference

Vender RB, Andriessen A, Barankin B, et al. Cohort using a ceramides containing cleanser and cream with salicylic acid for dry, flaking, and scaling skin conditions. J Drugs Dermatol. 2019;18(1):80-85.

February 22, 2019

Hyperhidrosis was more prevalent among both men and women who were obese compared with those of normal weight.

Obesity in adolescents is associated with an increased risk for hyperhidrosis, according to a study recently published in the Journal of the American Academy of Dermatology.

This cross-sectional study included 2,772,468 adolescent Israeli individuals, 59.6% of whom were male. These individuals had enrolled in compulsory military service between 1967 and 2016 and were given a medical examination at a mean age of 17.3 years old. Hyperhidrosis was diagnosed by a dermatologist, which was present among 1.5% of individuals (n=42,539; 68.9% men).

Hyperhidrosis was more prevalent among both men and women who were obese compared with those of normal weight (2.9% vs 1.5% and 1.6% vs 1.1%, respectively). The adjusted odds ratio (aOR) for overweight vs normal weight men was 1.3 (95% CI, 1.25-1.34), and the aOR for obese vs normal weight men 1.4 (95% CI, 1.34-1.46). For overweight and obese women vs normal weight women, the aORs were 1.1 (95% CI, 1.04-1.17) and 1.2 (95% CI, 1.07-1.27), respectively.

With each increasing body mass index unit, men experienced a 3.2% (95% CI, 1.029-1.035%) increase in risk for hyperhidrosis, and women experienced a 1.5% (95% CI, 1.010-1.019%) increase in risk. Among participants whose health was unimpaired, these results were accentuated. Among participants with obesity, those with class II obesity had higher odds ratios: 1.5 (95% CI, 1.3-1.6) for men and 1.4 (95% CI, 1.2-1.7) for women.

Limitations to this study included a lack of data on primary vs secondary hyperhidrosis, as well as a timespan of 5 decades over which hyperhidrosis criteria could have evolved.

The study researchers concluded that “obesity is associated with hyperhidrosis among adolescents. Future studies are required to further investigate this association and to determine whether weight reduction may have a therapeutic role in these patients.”

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Reference

Astman N, Friedberg I, Wikstrom J, et al. The association between obesity and hyperhidrosis: a nationwide, cross sectional study of 2.77 million Israeli adolescents [published online January 21, 2019]. J Am Acad Dermatol. doi: 10.1016/j.jaad.2019.01.019

February 22, 2019

Nearly nearly 50% of patients with psoriasis are not appropriately screened or treated for depression,

Significantly increased risks for depression and suicidality have been found in patients with psoriasis, although nearly 50% of this population is not recognized or identified by dermatologists, according to a letter published in Journal of the American Academy of Dermatology.

In this cross-sectional, anonymous survey study, 74 dermatologists based in the United States completed surveys online or in-person at dermatologic meetings, which included the 2018 American Academy of Dermatology Annual Meeting, the New York University Advances in Dermatology Symposium, and the monthly meetings of Dermatologic Society of Greater New York.

More than half (57%) of participants agreed or strongly agreed that there is an unfulfilled need for patients with psoriasis to undergo frequent monitoring for depression and suicidal ideation and behavior, but only 27% include questions about mood in the majority of clinical encounters. Of this amount, only 7% use a depression screening tool for asking about mood (mean score, 7.8±2.5), discussing depression (mean score, 7.4±2.5), and referring to mental health services (mean score, 8.2±2.3). 

The mean score for asking about suicidal ideation and behavior  was only 6.3±2.8. There was significantly increased comfort among physicians when asking and talking about depression and suicidal ideation and behavior when using a screening tool. The frequency of screening was positively correlated with comfort asking and talking about depression and suicidal ideation and behavior. Finally, there was also a significant positive correlation between the number of systemic medications prescribed by providers and screening frequency.

This study was limited by a relatively small sample size and reliance on self-reported assessments. There is potential for selection and non-response bias due to the level of motivation of responders to participate.

Psoriasis has been independently associated with major depression in the literature; this underscores the importance of being able to identify depression and SIB among patients with psoriasis. The findings of this study highlight an important knowledge and practice gap. The authors suggest that “[f]urther medical education on the available depression screening tools, such as the [Patient Health Questionnaire-2] and how to implement them into practice may help improve care and more completely address the needs of psoriasis patients.”

Dr Ho declared affiliation with the pharmaceutical industry. Please refer to reference for a complete list of disclosures.

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Reference

Liang SE, Cohen JM, Ho RS. Screening for depression and suicidality in psoriasis patients: a survey of U.S. dermatologists [published online January 22, 2019]. J Am Acad Dermatol. doi: 10.1016/j.jaad.2019.01.025