Skin and Cancer Associates - Hallandale Beach

December 26, 2018

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.

December 24, 2018

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

December 21, 2018

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

December 21, 2018

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.

December 19, 2018

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

December 18, 2018

Guselkumab is an IL-23 inhibitor; secukinumab is an IL-17A inhibitor

Guselkumab (Tremfya; Janssen), an interleukin (IL)-23 inhibitor, was found to be superior to secukinumab (Cosentyx; Novartis), an IL-17A inhibitor, in achieving Psoriasis Area Severity Index [PASI]) 90 responses in patients with moderate to severe plaque psoriasis, according to data from a Phase 3 head-to-head trial.

In the ECLIPSE study (N=1048), patients were randomized to receive guselkumab 100mg at weeks 0, 4, and 12 followed by every 8-week dosing or secukinumab 300mg at weeks 0, 1, 2 3, 4 followed by every 4-week dosing. The primary endpoint was the proportion of patients achieving a PASI 90 response at week 48.

Results showed that at 84.5% of patients treated with guselkumab achieved at least 90% improvement in their baseline PASI score vs 70% of patients treated with secukinumab (P <.001) at week 48. In addition, guselkumab was found to be noninferior to secukinumab in achieving PASI 75 response at weeks 12 and 48 (84.6% vs 80.2%; P <.001) but was not superior (P =.062). 

Other secondary endpoints included PASI 100 response and Investigator’s Global Assessment (IGA) scores of 0 and 1. At week 48, a greater proportion of guselkumab-treated patients achieved PASI 100 vs secukinumab-treated patients (58.2% vs 48.4%).  Also, 62.2% of patients receiving guselkumab achieved IGA score of 0 vs 50.4% of patients who received secukinumab; 85.0% and 74.9% of patients in the guselkumab and secukinumab  groups achieved IGA score of 1, respectively (all comparisons with nominal P ≤.001). Regarding tolerability, treatment discontinuation was seen in 5.1% of guselkumab patients and 9.3% of secukinumab patients. 

“The response-over-time curves show that maximum response rates with Tremfya are achieved after 6 months and are maintained over time through 1 year, achieving superiority at the primary endpoint of the study,” said lead study investigator Richard Langley, MD, FRCPC, Professor, Division of Clinical Dermatology & Cutaneous Science, Department of Medicine, Dalhousie University. “Results of the study confirm a slightly more rapid onset of response with Cosentyx, but importantly, in a chronic disease like psoriasis, these data provide new insights into comparative longer-term efficacy.”

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For more information call (800) 526-7736 or visit Janssen.com.

December 18, 2018

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

December 17, 2018

Two network meta-analysis studies provide validity and usefulness of systemic therapies to treat psoriasis.

Findings from a study published in the British Journal of Dermatology that analyzed 2 previously published network meta-analyses (NMA) support the validity and usefulness of systemic therapies for moderate to severe psoriasis.

This study analyzed 2 previously published NMAs that assessed systemic therapies for moderate to severe psoriasis with the outcome of either “‘clear/nearly clear’ and withdrawals from adverse events” (ZJL Study) or “improvement of 90% or more on the Psoriasis Area and Severity Index (PASI 90) and serious adverse events” (ES study). Both NMAs performed comparative analyses on the efficacy and safety of systemic therapies (ie, biologics and methotrexate in the ZJL study or traditional systemics or new oral agents in the ES study) to treat moderate to severe psoriasis. The study populations included mostly adults.

The authors noted that both previously published studies are “of high quality and provide a comprehensive summary of the evidence base and treatment effects.”

They added that both studies used best practices for conducting and reporting the systematic reviews. Both studies also used the Cochrane risk of bias tool, wherein 10 of 38 total trials had similar ratings for all domains. Discrepancies in the validity and analysis sensitivity of the assessment tool and incongruities in the analysis of the “study-level data using NMA models with random-effects for the treatment parameters” were noted.

The authors also discussed the conditional nature in treatment rankings, which is dependent upon the included treatments for comparison, and cumulative rankings previously published. Finally, the authors highlighted the correct use of a random-effect NMA model to address heterogeneity but questioned the previous studies’ analyses for consistency.

The investigators identified the following as study limitations: the need for a longer time frame for outcomes assessment, the lack of testing of newly available agents since the publication of the previous 2 studies, and the lack of real-world data to improve generalizability. 

Taken together, the authors noted the validity and usefulness of the results from both network meta-analyses in regard to “clearing of psoriasis skin lesions at relevant time-points and improvement in quality of life” for patients affected by moderate to severe psoriasis.

Disclosures: Multiple authors declare affiliations with the pharmaceutical industry. Please refer to original reference for a full list of authors’ disclosures.

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Reference

Ellis AG, Flohr C, Drucker AM. Network meta-analyses of systemic treatments for psoriasis: a critical appraisal [published online October 22, 2018]. Br J Dermatol. doi: 10.1111/bjd.17335

December 17, 2018

Investigators analyzed demographics, rates of reaction to nickel, strength of nickel reactions, and nickel allergy sources.

Nickel sensitivity has significantly increased in the last 20 years in North America, and incidence varies by demographics, according to a results from a retrospective, cross-sectional analysis published in the Journal of the American Academy of Dermatology.

Data from 44,097 patients patch-tested to gauge sensitivity to nickel (nickel sulfate hexahydrate 2.5% petrolatum) were collected from 1994 to 2014. Additional variables included sex, age, race, atopy (hay fever, eczema, asthma), dermatitis sites (≥3), and clinical relevance. Up to 3 final diagnoses and occupational relatedness were also recorded in the dataset.

Nickel sensitivity was defined as a mild (nonvesicular/erythematous/infiltrated/possible papules), strong (edematous/vesicular), or extreme (spreading/bullous/ulcerative) reaction to nickel at second reading.

Nickel sensitivity increased significantly over the study period, from 14.3% in 1994-1996 to 20.1% in 2013-2014 (P <.0001), with the overall frequency at 17.5% from 1994 to 2014 (7729/44,097 patients). Patients with nickel sensitivity were more likely to be female (relative risk [RR] 3.13; 95% CI, 2.94-3.33), ≤18 years of age (RR 1.49; 95% CI, 1.39-1.61), nonwhite, (RR 1.19; 95% CI, 1.14-1.27), and/or atopic (RR 1.09; 95% CI, 1.05-1.14).

Eczema (RR 1.10; 95% CI, 1.05-1.15) and asthma (RR 1.11; 95% CI, 1.05-1.17) were significantly associated with nickel sensitivity, though hay fever was not. Patients presenting with nickel sensitivity were significantly more likely to have a final diagnosis of allergic contact dermatitis (RR 2.31; 95% CI, 2.20-2.43).

Current clinical relevance increased significantly, from 44.1% in 1994-1996 to 51.6% in 2013-2014 (P <.0001). Occupational relatedness decreased from 7.9% in 1994-1996 to 1.9% in 2013-2014 (P <.0001). Jewelry consistently remained the most common source of nickel dermatitis, even after sources were stratified by age and sex.

Limitations to this study include the inability to follow up with the patients because of the study design and that potential sources of nickel dermatitis were limited to those with codes in the North American Contact Dermatitis Group source list.

Disclosures: Several authors acknowledge competing interests; please see original reference for a full list of authors’ disclosures.

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Reference

Warshaw EM, Zhang AJ, DeKoven JG, et al. Epidemiology of nickel sensitivity: retrospective cross-sectional analysis of North American Contact Dermatitis Group (NACDG) data 1994-2014 [published online October 18, 2018]. J Am Acad Dermatol. doi: 10.1016/j.jaad.2018.09.058

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