Infection was the most common adverse medical condition across the 4 cohorts.

In patients with psoriasis, the use of biologic therapies compared with conventional systemic therapies (CST)/topical therapies is associated with a similar or lower risk for developing adverse medical conditions, according to study results published in the Journal of Drugs in Dermatology.

In this retrospective cohort study, data from a large US administrative claims database were used to explore the real-world risk for development of adverse medical conditions in adult patients with psoriasis treated with CST/topical therapies vs patients treated with biologic agents. Participants were classified into cohorts based on the treatment initiated on the index date: adalimumab, etanercept, infliximab, ustekinumab, or CST/topical therapies. Incident adverse medical conditions identified while on treatment from diagnoses recorded in medical claims included infections, malignancies (skin and nonskin), respiratory disease, mental disorders, and abnormal test results.

The following assessments were made: adverse medical condition risk with adalimumab, etanercept, and ustekinumab separately vs CST/topical therapies and adverse medical condition risk with adalimumab vs other biologic agents (etanercept, infliximab, and ustekinumab combined).

A total of 42,981 patients were identified (adalimumab: n=5197; etanercept: n=3311; infliximab: n=187; ustekinumab: n=1370; CST/topical therapies: n=32,916). Across the various cohorts, 46.2% to 53.1% of the participants were women, median age was 46 to 50, and the median duration of follow-up was 3.3 to 7.9 months.

Infection was the most commonly reported adverse medical condition in all cohorts (28.7% to 41.8% of patients). Adalimumab, etanercept, and ustekinumab were all associated with a significantly lower risk for infection compared with CST/topical therapies (adjusted hazard ratio [aHR] 0.93, 0.92, and 0.86, respectively; P <.05 for all).

Moreover, treatment with adalimumab was associated with a significantly lower risk for malignancies (aHR 0.71; P <.05) and treatment with etanercept was associated with a significantly lower risk for respiratory disease (aHR 0.80; P <.05). When adalimumab was compared with other biologic agents, a similar safety profile was reported with respect to the adverse medical conditions that were evaluated.

The investigators concluded that additional studies with longer follow-up periods are warranted in order to capture the long-term effect of psoriasis therapies on an individual’s risk for adverse medical conditions.

Disclosures: Design, study conduct, and financial support for the study were provided by AbbVie; AbbVie participated in the interpretation of the data, review, and approval of the manuscript. Multiple authors disclosed affiliations with pharmaceutical companies. See the reference for complete disclosure information.

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Reference

Wu JJ, Armstrong A, Singh R, et al. Adverse medical conditions across treatment options in patients with psoriasis: a claims-based analysis. J Drugs Dermatol. 2018;17(11):1211-1218.

Generic topical dermatologic drugs had a median percentage price decrease of 5.3% but a mean percentage price increase of 85.1% from 2013 to 2016.

Policies that generate increased market competition between topical dermatologic generic agents with a limited number of manufacturers may, in turn, lead to long-term price reductions. The negative association between the change in drug prices and the median number of manufacturers of these topical generic agents signifies a role for market competition in controlling costs within the dermatology armamentarium, according to the results of a retrospective cost analysis published in JAMA Dermatology.

The investigators sought to describe the association between changes in drug prices and the number of US Food and Drug Administration (FDA)-approved manufacturers among the most frequently used generic topical dermatologic products. They used cumulative annual claims data from the Medicare Part D Prescriber Public User File to identify 597 drugs prescribed by dermatologists with >10 claims. The FDA Orange Book was used to determine the number of manufacturers. The National Average Drug Acquisition Cost (NADAC) database provided the price per unit of each product.

Data were collected between 2013 and 2016. Drugs that were not topically administered, were non-dermatologic, were missing NADAC data, were lacking a generic formulation, or had <400 claims were excluded from the study. The primary study outcomes were the per-unit drug price and the number of FDA-approved manufacturers. Pricing measures, adjusted for inflation, were reported in 2016 US dollars.

A total of 116 topical dermatologic generic products comprised the current analysis, which represented 70.5% of the total Medicare Part D dermatologist-coded claims from calendar year 2015. Whereas drug formulations with 1 or 2 manufacturers during the study period maintained a median percentage price increase of 12.7%, those with  >6 manufacturers exhibited a median percentage decrease in price of 20.5%.

Moreover, products with 1 to 2 manufacturers had a 20.6%, 19.5%, and 33.2% higher percentage increase in price compared with those formulations with 3 to 4 manufacturers, 5 to 6 manufacturers, and >6 manufacturers, respectively. A statistically significant inverse relationship was reported between the percentage change in drug price and the median number of manufacturers (P =.005).

The investigators concluded that the findings from this study support policies that facilitate robust market competition among topical dermatologic generic agents produced by a small number of manufacturers, which may help pave the way for long-term price reductions.

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Reference

Li DG, Joyce C, Mostaghimi A. Association between market competition and prices of generic topical dermatology drugs. JAMA Dermatol. 2018;154(12)1441-1446.

Patients with moderate to severe plaque psoriasis typically require long-term treatment to achieve disease control.

According to study results published in the Journal of the European Academy of Dermatology and Venereology, long-term treatment with ixekizumab is not associated with any new safety signals and should be considered acceptably safe and tolerable for the treatment of moderate to severe plaque psoriasis.

Previous studies have shown ixekizumab to be effective with no unexpected safety signals to treat chronic psoriasis in a short-term treatment period up to 24 weeks. The investigators of this study sought to evaluate the long-term safety and tolerability of ixekizumab for treating patients with moderate to severe plaque psoriasis for up to 3 years.

The present analysis reported the cumulative safety data on up to 319 weeks of ixekizumab exposure in a cohort of 5689 adults with moderate to severe psoriasis recruited from 11 clinical studies. The primary outcomes were treatment-emergent adverse events, including serious infections, oral candidiasis, major adverse cerebrocardiovascular events, non-melanoma skin cancer, malignancies, and inflammatory bowel disease. Adjusting for exposure period, the investigators reported the incidence rates (IR) per 100 patient-years; frequencies and exposure-adjusted incidence rates were summarized by 12-week intervals through 156 weeks (3 years).

Of the 5689 participants, 3787 received ixekizumab treatment for at least 1 year, 3162 for at least 2 years, and 1659 for at least 3 years. The participants accounted for 12,061.5 patient years of overall ixekizumab exposure. Over 156 weeks, a total of 4775 (83.9%) patients reported treatment-related adverse events. The most commonly reported adverse events were similar to previous reports of short-term exposure, including infections (28.7 IR; 95% CI, 27.8-29.7), injection-site reactions (7.0 IR; 95% CI, 6.5-7.5), and allergic reactions/hypersensitivities (6.1 IR; 95% CI, 5.6-6.5).

The incidence rate of opportunistic infections was 1.8 (95% CI, 1.6-2.1), the most common being mucocutaneous candidiasis, with an incidence rate of oral Candida infection of 0.9 (95% CI, 0.8-1.1). The frequency and incidence rates of adverse events did not increase over time with longer ixekizumab exposure, nor did the investigators identify a trend of increasing incidence rates for adverse events of special interest over the study period. Serious adverse events were reported in 11.8% of patients, causing 6.7% of patients to discontinue treatment; death occurred in 23 (0.4%) patients.

As patients with moderate to severe plaque psoriasis typically require long-term treatment to achieve disease control, researchers concluded that ixekizumab had an acceptable long-term safety profile consistent with previously reported short-term safety data in treating this patient population.

Disclosures: This study was sponsored by Eli Lilly and Company.

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Reference

Langley RG, Kimball AB, Nakagawa H, et al. Long-term safety profile of ixekizumab in patients with moderate-to-severe plaque psoriasis: an integrated analysis from 11 clinical trials [published online September 10, 2018]. J Eur Acad Dermatol Venereol. doi:10.1111/jdv.15242

It is unclear whether the positive skin changes are a result of the combination therapy or microneedling alone.

Using a multi-ingredient antiaging facial moisturizer before and after radiofrequency microneedling is associated with significant improvements in skin attributes, such as radiance, tone, and smoothness, according to study results published in the Journal of Cosmetic Dermatology.

Researchers assessed the safety, tolerability, and efficacy of the multi‐ingredient antiaging face moisturizer (DEJ face cream®) in an open-label clinical study. They evaluated women who used the moisturizer for 2 weeks, received a radiofrequency microneedling procedure, and then used the moisturizer again for another 4 weeks. Clinical evaluations using the Glogau Wrinkle Scale, full‐face global skin attributes, and tolerability assessments were performed at each visit, and patient evaluations were completed at the final visit to assess procedure satisfaction. Data and pictures were collected at baseline, week 2, week 4, and week 6.

Of the 15 study participants, the average age was 51, with a Fitzpatrick skin type I-IV and mild to moderate wrinkles. The median Glogau score improved most significantly from week 4 to week 6 (P =.0293 between baseline and week 6). In skin attribute changes from baseline to week 6, 80% of the participants saw a 4-fold improvement in radiance (overall improvement in radiance P =.0005); 73% saw a 12-fold improvement in tone (overall improvement in tone P =.001); 87% saw a 7-fold improvement in skin visual smoothness (overall improvement in skin visual smoothness P =.0002); 87% saw a 7-fold improvement in skin texture (overall improvement in skin texture P =.0002); 73% saw a 4-fold improvement in redness (overall improvement in redness P =.0195); and 27% of patients achieved the best score associated with dryness at visit 4 compared with none and visit 1 (P =.0024). In all, 67% of patients saw a 6-fold improvement in overall appearance (overall improvement in appearance P =.0020).

After radiofrequency microneedling, erythema and edema increased significantly (P =.0002 and P =.0313, respectively), and while edema was completely resolved by week 4, one patient still had erythema at week 6. At the last visit, patient evaluation scores improved the most in overall improvement, brightness, texture, pigmentation, redness, and tightness, and 60% would recommend this procedure to family and friends. 

Future studies should incorporate a placebo or control arm and evaluate if radiofrequency microneedling is effective on its own or if the multi‐ingredient antiaging face moisturizer combination is necessary.

“It is unclear at this point whether the contribution of efficacy parameters is due to RF microneedling in combination with this multi-ingredient antiaging moisturizer or due to RF microneedling alone,” the authors said, noting that this would need to be the subject of future research.

Disclosure: This study was sponsored by Revision Skincare.

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Reference

Zahr AS, Kononov T, Sensing W, Biron JA, Gold MH. An open-label, single-site study to evaluate the tolerability, safety, and efficacy of using a novel facial moisturizer for preparation and accelerated healing pre and post a single full-face radiofrequency microneedling treatment [published online November 19, 2018]. J Cosmet Dermatol. doi: 10.1111/jocd.12817

Approval of the new indication was supported by data from KEYNOTE-017 trial which included 50 patients.

The Food and Drug Administration has granted accelerated approval to Keytruda (pembrolizumab; Merck) for the treatment of patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC). The accelerated approval was based on tumor response rate and durability of response; continued approval for this indication may be contingent upon verification of clinical benefit in the confirmatory trials. 

Approval of the new indication was supported by data from KEYNOTE-017 (NCT02267603), a multlicenter, non-randomized, open-label trial (N=50) of patients with recurrent locally advanced or metastatic MCC who had not received prior systemic therapy for their advanced disease. 

The major efficacy outcome measures were overall response rate (ORR) and response duration assessed by blinded independent central review per RECIST 1.1. 

The ORR was 56% (95% CI, 41, 70) of which 24% were complete response. Of the responders (n=28), 96% had a response duration lasting >6 months, and 54% had a response lasting >12 months. At the time of analysis, the median response duration was not reached. 

Fatigue, musculoskeletal pain, decreased appetite, pruritus, diarrhea, nausea, rash, pyrexia, cough, dyspnea, constipation, pain, and abdominal pain were the most common adverse reactions associated with Keytruda monotherapy. 

Keytruda, a human programmed death receptor-1 (PD-1) blocking antibody, is already approved to treat various colorectal, gynecologic, head and neck, lymphoma, skin, and respiratory cancers. It is available as 50mg/vial as a lyophilized powder for IV infusion, and as a 25mg/mL per vial solution fo IV infusion.

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For more information call (800) 672-6372 or visit Keytruda.com.

Overall, the participants reported that the facial exercise regimen was well tolerated, with 59% of the women indicating that the muscle contractions were very easy to perform.

A facial exercise regimen following botulinum toxin injections for glabella and forehead wrinkles may lead to faster improvement in facial wrinkles, according to the results of a randomized, controlled, crossover clinical trial. Findings were published in the Journal of the American Academy of Dermatology. 

The investigators sought to explore whether exercising facial muscles after injections of botulinum toxin into the forehead and glabellar rhytids is associated with more rapid improvement in wrinkle appearance compared with injections without exercise. Eligible study participants comprised women who were in good health and had been recruited from an urban-based dermatology practice. All participants had dynamic rhytids of the glabella and forehead. The women were randomly assigned to perform either a facial exercise regimen or to refrain from facial contractions for 4 hours following botulinum injections.

Two blinded dermatologist photoraters assessed forehead and glabella dynamic creases at baseline and on days 1, 2 3, 4, 7, and 14. Each of the women also assessed her own dynamic creases using a 7-point Subject Self-Evaluation Improvement Scale (–3 to +3). All participants were crossed over to the other arm at 7 months.

Of the 25 women who consented and enrolled in the study, 22 completed the study per protocol. The mean age of the participants was 46.7 years (range, 27 to 66 years). Both the dermatologists and the participants rated dynamic glabellar and static forehead wrinkles as significantly improved by day 3 when botulinum injection was followed by facial contractions (dermatologists’ ratings: P =.002 and P =.02, respectively; participants’ ratings: P =.01 and P =.02, respectively).

The women also reported significantly noticeable glabellar improvement by day 2 to 3 when the injection was followed by facial exercise, compared with day 3 to 4 without facial exercise (P =.02). In fact, a significant advantage was detected in the exercise group as early as day 3, at which time participants’ self-evaluation wrinkle scores increased by approximately twice as much among the exercisers compared with the nonexercisers. The overall degree of effect was the same in both the exercise and nonexercise groups at 14 days. Further, the duration of action did not appear to differ between the exercise and nonexercise arms.

Overall, the participants reported that the facial exercise regimen was well tolerated, with 59% of the women indicating that the muscle contractions were very easy to perform. Of the participants, 68% thought that the contractions sped up the onset of action and increased the toxin efficiency and did not have an impact on the duration of effectiveness.

The investigators concluded that based on the results of this analysis, future studies could include men and could be performed for other neuromodulator agents, at different injection sites, and using different types of exercise regimens to establish minimal needs.

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Reference

Alam M, Geisler A, Warycha M, et al. Effect of post-injection facial exercise on time of onset of botulinum toxin for glabella and forehead wrinkles; a randomized controlled, crossover clinical trial [published online October 1, 2018]. J Am Acad Dermatol. doi: 10.1016/j/jaad.2018.10.013

The mean improvement from baseline in the SCORAD Itch VAS was significantly greater in patients who received upadacitinib 7.5 mg vs placebo.

SEATTLE — Upadacitinib, a selective janus kinase-1 inhibitor, was associated with early improvements in pruritus when administered for 16 weeks at once-daily 7.5 mg, 15 mg, or 30 mg in patients with moderate to severe atopic dermatitis (AD), according to research findings presented at the 2018 Annual Scientific Meeting of the American College of Allergy, Asthma and Immunology held in Seattle, November 15-19, 2018.

Adult patients with moderate-to-severe AD who were either contraindicated for topical treatment or whose disease was not adequately controlled by topical treatment were enrolled in this clinical trial (N=166; ClinicalTrials.gov Identifier: NCT02925117). Overall, patients presented with an Eczema Area and Severity Index score of ≥16, a body surface area of ≥10%, and an Investigator Global Assessment Scale score of ≥3. Researchers randomly assigned patients to receive either once-daily upadacitinib 7.5 mg (n=42), 15 mg (n=42), or 30 mg (n=42) or placebo (n=40).

The Scoring Atopic Dermatitis (SCORAD) Itch Visual Analog Scale (VAS), Patient Oriented Eczema Measure (POEM) itch score (question #1), and pruritus Numerical Rating Scale (NRS) were used to assess changes in patient-reported pruritus. By week 16, the mean improvement from baseline in the SCORAD Itch VAS (range 0-10) was significantly greater in patients randomly assigned to receive upadacitinib 7.5 mg vs placebo (P <.05). In addition, patients reported significantly greater pruritus improvements in the 15 mg (P >.05) and 30 mg (P =.05) groups compared with placebo.

According to the researchers, “the positive benefit/risk profile of upadacitinib supports proceeding to phase 3 trials in AD.”

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Reference

Beck L, Hong C, Hu X, et al. Upadacitinib effect on pruritus in moderate-to-severe atopic dermatitis; from a phase 2B randomized, placebo-controlled trial. Presented at: the Annual Scientific Meeting of the American College of Allergy, Asthma, and Immunology; November 15-19, 2018; Seattle, WA. Abstract D500.

It is crucial to identify effective strategies for improving the management and control of pruritus.

Elucidating the healthcare costs associated with pruritus is critical, considering the association of itch with numerous chronic diseases. Incremental costs linked with pruritus seem to have remained steady over the years, but expenditures resulting from the condition appear to be shifting from outpatient and inpatient settings to the emergency department and home health services.

For this study, researchers examined pruritus-associated healthcare expenditures in the United States using 9 years of data from the Medical Expenditure Panel Survey for 2007 through 2015. Findings from the current retrospective cohort study were published in the Journal of the American Academy of Dermatology. 

The investigators sought to provide nationally representative estimates of the incremental healthcare burden of pruritus, controlling for sociodemographic characteristics and patient comorbidities. They used the definition of pruritus from the International Classification of Diseases, 9th Revision, Clinical Modification code 698. A 2-part linear regression model was used to account for the high concentration of zero expenditures reported in the data. The model is used to estimate expenditure ratios.

A total of 637 patients with pruritus and 288,061 individuals without pruritus were included in the study sample. The following groups were all significantly more likely to have pruritus: women, older adults, Medicaid/Medicare patients, non-white patients, patients with more comorbidities, and patients with less education (P <.001 for all). After controlling for all sociodemographic factors and the Charlson Comorbidity Index, the cost of care among patients with pruritus was 1.64 times as high as costs among those without the condition (P <.001).

The analysis showed that ultimately, pruritus can become a significant burden to both medical and financial health. Patients with pruritus are estimated to incur $4843.68 more in annual healthcare costs compared with those without pruritus, even after controlling for sociodemographic factors and comorbidities.

A major limitation of the study is that unmeasured confounders may have overestimated the incremental cost associated with pruritus, taking into account the demographic differences between the evaluated patient populations with and without pruritus.

The investigators concluded that as overall healthcare costs continue to rise, it is even more critical to identify effective strategies to improve the management and control of pruritus.

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Reference

Tripathi R, Knusel KD, Ezaldein HH, Bordeaux JS, Scott JF. The cost of an itch: a nationally representative retrospective cohort study of pruritus-associated healthcare expenditure in the United States [published online October 23, 2018]. J Am Acad Dermatol. doi: 10.1016/j.jaad.2018.10.025

Participants noted improvements in facial texture and wrinkles after injections of platelet-rich plasma.

Platelet-rich plasma (PRP) injections may at least temporarily improve texture of photoaged skin compared with saline injections, according to a study recently published in JAMA Dermatology.

In this parallel, split-face, randomized clinical trial with 1:1 allocation, participants and raters were masked to participant groupings. Nineteen participants between the ages of 18 and 70 years with bilateral cheek rhytids of Glogau class II or greater received 3 mL intradermal injections of PRP to 1 cheek and 3 mL sterile normal saline injections in the contralateral cheek. Injections were placed 1 cm apart at the level of the mid-dermis with a 25-gauge needle in aliquots of 0.02 mL per puncture from the zygomatic area to mandibular area and from the nasolabial folds to the preauricular area. Digital photographs taken at 2-week and 3-month follow-up visits were compared with baseline digital photographs by 2 dermatologists who assigned photoaging scores. Participants also completed self-assessment questionnaires and adverse events were recorded at all follow-up visits. Additionally, at 6 months, patients completed an overall satisfaction questionnaire, and a telephone follow-up was conducted at 12 months.

Mean photoaging scores, based on ratings from the 2 dermatologists, showed no significant difference between PRP and normal saline for all clinical variables, which included fine lines, mottled pigmentation, roughness, and sallowness. Participants rated the PRP-treated side after 6 months of injections as significantly more improved compared with the saline-treated side for texture (mean [SD] self-assessment score, 2.00 [1.20] vs 1.21 [0.54]; P =.02) and wrinkles (mean [SD] self-assessment score, 1.74 [0.99] vs 1.21 [0.54]; P =.03). Self-assessment scores for pigmentations and telangiectasias were nominally but not significantly improved. No serious adverse events were reported.

Early patient termination and low sample size was a limitation of this study; multiple sessions of PRP injections arguably could produce a greater cumulative benefit.

The study researchers concluded that PRP may reduce visible signs of photoaging in patients seeking facial rejuvenation but larger studies are needed for further analysis.

Disclosures: One author declares associations with the pharmaceutical industry. Please see original reference for a full list of authors’ disclosures.

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Reference

Alam M, Hughart R, Champlain A, et al. Effect of platelet-rich plasma injection for rejuvenation of photoaged facial skin: a randomized clinical trial [published online November 7, 2018]. JAMA Dermatol. doi:10.1001/jamadermatol.2018.3977

The least important item to patients was “be able to lead a normal working life.”

Women with psoriasis have higher treatment expectations and more specific needs than men with psoriasis, with particular concern for everyday productivity, sleep quality, and depression, according to study results published in the Journal of the European Academy of Dermatology and Venerology. Older patients with psoriasis also have different needs and expectations compared with younger patients.

Most clinicians regard patient needs as a key driver of treatment decisions, but these needs are rarely systematically investigated. In the current study, researchers analyzed patient needs and expectations using the national psoriasis registries of Switzerland (Swiss Dermatology Network of Targeted Therapies [SDNTT]; ClinicalTrials.gov identifier: NCT01706692) and Germany (PsoBest; ClinicalTrials.gov identifier: NCT01848028), with respect to age, gender, and treatment choice. These real-life data correspond to patient experiences in routine care between 2008 and 2016, with a mean follow-up of 7.5 months.

A total of 5343 patients (59.6% male, mean age 47.6±14.5 years at baseline) were included in the analyses (449 from SDNTT and 4894 from PsoBest). The overall most important patient needs cited were to see skin improvements quickly and to have all skin defects healed, both of which were rated as “quite/very important” by 94.0% of patients.

Although social needs such as “to be comfortable showing yourself more in public” were of greater concern for patients <65 years old than patients >65 (mean Patient Needs Questionnaire [PNQ] score of 3.1 vs 2.6, P ≤.001), patients >65 were more concerned with side effects (mean PNQ 2.9 vs 2.8, P ≤.031), sleep quality (mean PNQ 2.2 vs 2.1, P ≤.024), and being less dependent on medical visits (mean PNQ 3.2 vs 3.1, P ≤.001).

Women rated 20 out of 25 items as significantly more important than men, with everyday productivity, sleep quality, and depression showing the greatest differences.

Study investigators suggest “for treatment decisions, individual patient needs should be examined to identify and appropriately address patient-derived concerns. Some needs statements showed more distinct answer patterns than others, leading to a higher variance. A better understanding of patient needs could help physicians achieve better therapy outcomes, higher patient satisfaction and quality of care.”

Disclosures: The registries used in this study are supported by AbbVie, Amgen, Almirall, Biogen, Celgene, Hexal, Janssen-Cilag, LEO Pharma, Eli Lilly, medac, Novartis, and Pfizer. Multiple authors disclosed affiliations with pharmaceutical companies. See the reference for complete disclosure information. 

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Reference

Maul JT, Navarini AA, Sommer R, et al. Gender and age significantly determine patient needs and treatment goals in psoriasis – a lesson for practice [published online November 2, 2018]. J Eur Acad Dermatol Venereol. doi: 10.1111/jdv.15324